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41 total articles Sweet metabolic surrender. Stanhope and colleagues examined the effects of prolonged consumption of fructose- or glucose-sweetened beverages on lipid metabolism, insulin sensitivity, and adiposity in overweight and obese adults (page 1322). The two sugars had divergent metabolic effects. The authors found that consumption of fructose- but not glucose-sweetened beverages increased de novo hepatic lipogenesis and insulin resistance. Despite comparable weight gain in both groups of subjects, intra-abdominal fat volume was only increased in subjects consuming fructose. In the two years that I have been Editor in Chief of the JCI, the editors and I have sent approximately 2,500 papers for external review. The referee reports that we’ve received have spanned the spectrum from incredibly insightful to completely unhelpful. Together with a longer piece immediately following this editorial, I would like to reflect on what I think makes a good review. Laurence A. Turka Most scientists learn how to review papers by being thrown into the deep end of the pool: here’s a paper, write a review. Perhaps this is not the best way to keep an enterprise afloat. But what should be included in a review? What should the tone of a review be? Here I want to outline the specifics of what we at the JCI are looking for in a referee report. Ushma S. Neill Translation of novel therapies for type 1 diabetes and other autoimmune diseases to the clinic has been slow despite significant new initiatives from funding agencies. One reason for this is that different incentives drive industry, academia, and funding bodies. These communities therefore lack common goals and often communicate poorly, resulting in unintended obstacles that hamper progress in efficiently translating basic scientific discoveries into medical practice. Here, based on our own personal experiences, we discuss some of the drivers within each community that cause these problems, existing mechanisms to facilitate the translation of science into medical practice, and remaining issues that need to be solved. Matthias von Herrath, Andrew Chan SLE, a chronic, multisystem autoimmune disorder with a broad range of symptoms, involves defective B cell selection and elimination of self-reactive B cells. B lymphocyte stimulator (BLyS), a soluble ligand of the TNF cytokine family, is a prominent factor in B cell differentiation, homeostasis, and selection. BLyS levels affect survival signals and selective apoptosis of autoantibody-producing B cells. High levels of BLyS may relax B cell selection and contribute to autoantibody production, exacerbating the SLE disease state. This review discusses the mechanism of BLyS action on B cells, its role in SLE, and specific targeting of BLyS in the treatment of SLE. Michael P. Cancro, David P. D’Cruz, Munther A. Khamashta Little is known about the potential role of T cells in the inflammatory renal disease glomerulonephritis (GN). GN has been historically viewed as a product of immune complex–mediated complement activation, and the presence of autoantibodies made identifying T cell–specific effector contributions difficult to elucidate. In this issue of the JCI, Heymann et al. generate what they believe to be a novel, transgenic murine model of GN, demonstrating a direct role for CD8+ T cells, activated CD4+ T cells, and DCs in the pathogenesis of GN (see the related article, doi:10.1172/JCI38399). Alfred H.J. Kim, Mary A. Markiewicz, Andrey S. Shaw Gain-of-function mutations in FGF receptor 3 (FGFR3) have been implicated in severe skeletal dysplasias and in a variety of cancers. In their study in this issue of the JCI, Qing et al. used specific shRNA probes to demonstrate that FGFR3 functions as an important driver of bladder carcinoma cell proliferation (see the related article beginning on page 1216). A unique anti-FGFR3 mAb was shown to exhibit antitumor activity in human bladder carcinoma cells in vitro and in mouse bladder cancer or multiple myeloma xenograft tumor models bearing either wild-type or mutant FGFR3. These results suggest that clinical development of anti-FGFR3 mAbs should be considered for targeted therapy of cancer and other diseases. Yaron Hadari, Joseph Schlessinger Anti-TNF immunotherapy has revolutionized the treatment of some inflammatory diseases, such as RA. However, a major concern is that patients receiving this therapy have an increased risk of fungal and bacterial infection, particularly of reactivating latent tuberculosis (TB). In this issue of the JCI, in an effort to understand how anti-TNF immunotherapy affects host mechanisms required to control TB, Bruns and colleagues examined the effects of the anti-TNF therapeutic infliximab on Mycobacterium tuberculosis–specific human lymphocytes (see the related article beginning on page 1167). The authors report that a granulysin-expressing CD45RA+ subset of effector memory CD8+ T cells that contributes to the killing of intracellular M. tuberculosis is depleted in vivo by infliximab in patients with RA, and that these cells are susceptible to complement-mediated lysis in the presence of infliximab in vitro. The study provides insight into host defense mechanisms that act to control TB infection and how they are affected during anti-TNF immunotherapy for autoimmune disease. Elizabeth A. Miller, Joel D. Ernst Patients with systolic left ventricular dysfunction die progressively from congestive heart failure or die suddenly from cardiac arrhythmias. Myocardial hypertrophy is an early event in most forms of heart failure, but the majority of patients with myocardial hypertrophy do not develop heart failure. Developing improved therapies for targeting the cell signaling pathways that enable this deadly transition from early myocardial insult to heart failure and sudden death is a key goal for improving public health. In this issue of the JCI, Ling and colleagues provide new evidence that activation of the multifunctional Ca2+/calmodulin–dependent kinase IIδ is a decisive step on the path to heart failure in mice (see the related article beginning on page 1230). Mark E. Anderson HIV-1–associated nephropathy (HIVAN) is a common complication of HIV-1 infection, and its skewed incidence in certain ethnic groups suggests that there is a genetic basis to HIVAN susceptibility. In their study reported in this issue of the JCI, Papeta and colleagues used a combination of gene expression profiling and linkage analysis to identify three genomic loci that regulate a network of genes expressed by podocytes — cells that are crucial to the filtration of fluid and waste by the kidney (see the related article beginning on page 1178). Surprisingly, two of these loci confer disease susceptibility in a transgenic mouse model of HIVAN. This report confirms the central role of podocytes in the pathogenesis of HIVAN and demonstrates the power of this combination of genomic analysis techniques in elucidating the pathogenesis of glomerular disease. Susan E. Quaggin Coronary heart disease is a major cause of morbidity and mortality in Western societies. The metabolic syndrome, characterized by obesity, insulin resistance, elevated blood pressure, elevated triglycerides, and low levels of high-density lipoprotein cholesterol, confers substantial risk of coronary heart disease. Current pathogenetic models suggest that postprandial hyperlipidemia is one specific metabolic abnormality that is typically associated with increased morbidity. In this issue of the JCI, Stanhope and colleagues demonstrate that consumption of fructose-sweetened but not glucose-sweetened beverages for 10 weeks increases de novo lipid synthesis, promotes dyslipidemia, impairs insulin sensitivity, and increases visceral adiposity in overweight or obese adults (see the related article beginning on page 1322). Susanna M. Hofmann, Matthias H. Tschöp The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor β (ERβ). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ERβ/eNOS, ERβ/HIF-1α, or ERβ/HIF-2α combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes. Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins, with expression of eNOS plus ERβ and nuclear eNOS plus HIF-2α being the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in PCa progression. Our work has considerable clinical relevance, since it may enable the earlier diagnosis of aggressive PCa through routine biopsy assessment of eNOS, ERβ, and HIF-2α expression. Furthermore, proposing eNOS as a therapeutic target fosters innovative therapies for PCa with NO inhibitors, which are employed in preclinical trials in non-oncological diseases. Simona Nanni, Valentina Benvenuti, Annalisa Grasselli, Carmen Priolo, Aurora Aiello, Stefania Mattiussi, Claudia Colussi, Vittoria Lirangi, Barbara Illi, Manuela D’Eletto, Anna Maria Cianciulli, Michele Gallucci, Piero De Carli, Steno Sentinelli, Marcella Mottolese, Paolo Carlini, Lidia Strigari, Stephen Finn, Elke Mueller, Giorgio Arcangeli, Carlo Gaetano, Maurizio C. Capogrossi, Raffaele Perrone Donnorso, Silvia Bacchetti, Ada Sacchi, Alfredo Pontecorvi, Massimo Loda, Antonella Farsetti Imatinib mesylate (IM), a potent inhibitor of the BCR/ABL tyrosine kinase, has become standard first-line therapy for patients with chronic myeloid leukemia (CML), but the frequency of resistance increases in advancing stages of disease. Elimination of BCR/ABL-dependent intracellular signals triggers apoptosis, but it is unclear whether this activates additional cell survival and/or death pathways. We have shown here that IM induces autophagy in CML blast crisis cell lines, CML primary cells, and p210BCR/ABL-expressing myeloid precursor cells. IM-induced autophagy did not involve c-Abl or Bcl-2 activity but was associated with ER stress and was suppressed by depletion of intracellular Ca2+, suggesting it is mechanistically nonoverlapping with IM-induced apoptosis. We further demonstrated that suppression of autophagy using either pharmacological inhibitors or RNA interference of essential autophagy genes enhanced cell death induced by IM in cell lines and primary CML cells. Critically, the combination of a tyrosine kinase inhibitor (TKI), i.e., IM, nilotinib, or dasatinib, with inhibitors of autophagy resulted in near complete elimination of phenotypically and functionally defined CML stem cells. Together, these findings suggest that autophagy inhibitors may enhance the therapeutic effects of TKIs in the treatment of CML. Cristian Bellodi, Maria Rosa Lidonnici, Ashley Hamilton, G. Vignir Helgason, Angela Rachele Soliera, Mattia Ronchetti, Sara Galavotti, Kenneth W. Young, Tommaso Selmi, Rinat Yacobi, Richard A. Van Etten, Nick Donato, Ann Hunter, David Dinsdale, Elena Tirrò, Paolo Vigneri, Pierluigi Nicotera, Martin J. Dyer, Tessa Holyoake, Paolo Salomoni, Bruno Calabretta Long-term neurological deficiencies resulting from hippocampal cytotoxicity induced by cranial irradiation (IR) present a challenge in the treatment of primary and metastatic brain cancers, especially in children. Previously, we showed that lithium protected hippocampal neurons from IR-induced apoptosis and improved neurocognitive function in treated mice. Here, we demonstrate accelerated repair of IR-induced chromosomal double-strand breaks (DSBs) in lithium-treated neurons. Lithium treatment not only increased IR-induced DNA-dependent protein kinase (DNA-PK) threonine 2609 foci, a surrogate marker for activated nonhomologous end-joining (NHEJ) repair, but also enhanced double-strand DNA end-rejoining activity in hippocampal neurons. The increased NHEJ repair coincided with reduced numbers of IR-induced γ-H2AX foci, well-characterized in situ markers of DSBs. These findings were confirmed in vivo in irradiated mice. Consistent with a role of NHEJ repair in lithium-mediated neuroprotection, attenuation of IR-induced apoptosis of hippocampal neurons by lithium was dramatically abrogated when DNA-PK function was abolished genetically in SCID mice or inhibited biochemically by the DNA-PK inhibitor IC86621. Importantly, none of these findings were evident in glioma cancer cells. These results support our hypothesis that lithium protects hippocampal neurons by promoting the NHEJ repair–mediated DNA repair pathway and warrant future investigation of lithium-mediated neuroprotection during cranial IR, especially in the pediatric population. Eddy S. Yang, Hong Wang, Guochun Jiang, Somaira Nowsheen, Allie Fu, Dennis E. Hallahan, Fen Xia Leukocyte and platelet accumulation at sites of cerebral ischemia exacerbate cerebral damage. The ectoenzyme CD39 on the plasmalemma of endothelial cells metabolizes ADP to suppress platelet accumulation in the ischemic brain. However, the role of leukocyte surface CD39 in regulating monocyte and neutrophil trafficking in this setting is not known. Here we have demonstrated in mice what we believe to be a novel mechanism by which CD39 on monocytes and neutrophils regulates their own sequestration into ischemic cerebral tissue, by catabolizing nucleotides released by injured cells, thereby inhibiting their chemotaxis, adhesion, and transmigration. Bone marrow reconstitution and provision of an apyrase, an enzyme that hydrolyzes nucleoside tri- and diphosphates, each normalized ischemic leukosequestration and cerebral infarction in CD39-deficient mice. Leukocytes purified from Cd39–/– mice had a markedly diminished capacity to phosphohydrolyze adenine nucleotides and regulate platelet reactivity, suggesting that leukocyte ectoapyrases modulate the ambient vascular nucleotide milieu. Dissipation of ATP by CD39 reduced P2X7 receptor stimulation and thereby suppressed baseline leukocyte αMβ2-integrin expression. As αMβ2-integrin blockade reversed the postischemic, inflammatory phenotype of Cd39–/– mice, these data suggest that phosphohydrolytic activity on the leukocyte surface suppresses cell-cell interactions that would otherwise promote thrombosis or inflammation. These studies indicate that CD39 on both endothelial cells and leukocytes reduces inflammatory cell trafficking and platelet reactivity, with a consequent reduction in tissue injury following cerebral ischemic challenge. Matthew C. Hyman, Danica Petrovic-Djergovic, Scott H. Visovatti, Hui Liao, Sunitha Yanamadala, Diane Bouïs, Enming J. Su, Daniel A. Lawrence, M. Johan Broekman, Aaron J. Marcus, David J. Pinsky Neuropathy and myopathy can cause weakness during critical illness. To determine whether reduced excitability of peripheral nerves, rather than degeneration, is the mechanism underlying acute neuropathy in critically ill patients, we prospectively followed patients during the acute phase of critical illness and early recovery and assessed nerve conduction. During the period of early recovery from critical illness, patients recovered from neuropathy within days. This rapidly reversible neuropathy has not to our knowledge been previously described in critically ill patients and may be a novel type of neuropathy. In vivo intracellular recordings from dorsal root axons in septic rats revealed reduced action potential amplitude, demonstrating that reduced excitability of nerve was the mechanism underlying neuropathy. When action potentials were triggered by hyperpolarizing pulses, their amplitudes largely recovered, indicating that inactivation of sodium channels was an important contributor to reduced excitability. There was no depolarization of axon resting potential in septic rats, which ruled out a contribution of resting potential to the increased inactivation of sodium channels. Our data suggest that a hyperpolarized shift in the voltage dependence of sodium channel inactivation causes increased sodium inactivation and reduced excitability. Acquired sodium channelopathy may be the mechanism underlying acute neuropathy in critically ill patients. Kevin R. Novak, Paul Nardelli, Tim C. Cope, Gregory Filatov, Jonathan D. Glass, Jaffar Khan, Mark M. Rich HIF transcription factors (HIF-1 and HIF-2) are central mediators of cellular adaptation to hypoxia. Because the resting partial pressure of oxygen is low in the intestinal lumen, epithelial cells are believed to be mildly hypoxic. Having recently established a link between HIF and the iron-regulatory hormone hepcidin, we hypothesized that HIFs, stabilized in the hypoxic intestinal epithelium, may also play critical roles in regulating intestinal iron absorption. To explore this idea, we first established that the mouse duodenum, the site of iron absorption in the intestine, is hypoxic and generated conditional knockout mice that lacked either Hif1a or Hif2a specifically in the intestinal epithelium. Using these mice, we found that HIF-1α was not necessary for iron absorption, whereas HIF-2α played a crucial role in maintaining iron balance in the organism by directly regulating the transcription of the gene encoding divalent metal transporter 1 (DMT1), the principal intestinal iron transporter. Specific deletion of Hif2a led to a decrease in serum and liver iron levels and a marked decrease in liver hepcidin expression, indicating the involvement of an induced systemic response to counteract the iron deficiency. This finding may provide a basis for the development of new strategies, specifically in targeting HIF-2α, to improve iron homeostasis in patients with iron disorders. Maria Mastrogiannaki, Pavle Matak, Brian Keith, M. Celeste Simon, Sophie Vaulont, Carole Peyssonnaux The incidence of tuberculosis is increased during treatment of autoimmune diseases with anti-TNF antibodies. This is a significant clinical complication, but also provides a unique model to study immune mechanisms in human tuberculosis. Given the key role for cell-mediated immunity in host defense against Mycobacterium tuberculosis, we hypothesized that anti-TNF treatment impairs T cell–directed antimicrobial activity. Anti-TNF therapy reduced the expression in lymphocytes of perforin and granulysin, 2 components of the T cell–mediated antimicrobial response to intracellular pathogens. Specifically, M. tuberculosis–reactive CD8+CCR7–CD45RA+ effector memory T cells (TEMRA cells) expressed the highest levels of granulysin, lysed M. tuberculosis, and infected macrophages and mediated an antimicrobial activity against intracellular M. tuberculosis. Furthermore, TEMRA cells expressed cell surface TNF and bound the anti-TNF therapeutic infliximab in vitro, making them susceptible to complement-mediated lysis. Immune therapy with anti-TNF was associated with reduced numbers of CD8+ TEMRA cells and decreased antimicrobial activity against M. tuberculosis, which could be rescued by the addition of CD8+ TEMRA cells. These results suggest that anti-TNF therapy triggers a reduction of CD8+ TEMRA cells with antimicrobial activity against M. tuberculosis, providing insight into the mechanism whereby key effector T cell subsets contribute to host defense against tuberculosis. Heiko Bruns, Christoph Meinken, Philipp Schauenberg, Georg Härter, Peter Kern, Robert L. Modlin, Christian Antoni, Steffen Stenger Multiple studies have linked podocyte gene variants to diverse sporadic nephropathies, including HIV-1–associated nephropathy (HIVAN). We previously used linkage analysis to identify a major HIVAN susceptibility locus in mouse, HIVAN1. We performed expression quantitative trait locus (eQTL) analysis of podocyte genes in HIV-1 transgenic mice to gain further insight into genetic susceptibility to HIVAN. In 2 independent crosses, we found that transcript levels of the podocyte gene nephrosis 2 homolog (Nphs2), were heritable and controlled by an ancestral cis-eQTL that conferred a 3-fold variation in expression and produced reactive changes in other podocyte genes. In addition, Nphs2 expression was controlled by 2 trans-eQTLs that localized to the nephropathy susceptibility intervals HIVAN1 and HIVAN2. Transregulation of podocyte genes was observed in the absence of HIV-1 or glomerulosclerosis, indicating that nephropathy susceptibility alleles induce latent perturbations in the podocyte expression network. Presence of the HIV-1 transgene interfered with transregulation, demonstrating effects of gene-environment interactions on disease. These data demonstrate that transcript levels of Nphs2 and related podocyte-expressed genes are networked and suggest that the genetic lesions introduced by HIVAN susceptibility alleles perturb this regulatory pathway and transcriptional responses to HIV-1, increasing susceptibility to nephropathy. Natalia Papeta, Ka-Tak Chan, Sindhuri Prakash, Jeremiah Martino, Krzysztof Kiryluk, David Ballard, Leslie A. Bruggeman, Rachelle Frankel, Zongyu Zheng, Paul E. Klotman, Hongyu Zhao, Vivette D. D’Agati, Richard P. Lifton, Ali G. Gharavi Chronic bacterial airway infections are the major cause of mortality in cystic fibrosis (CF). Normal airway defenses include reflex stimulation of submucosal gland mucus secretion by sensory neurons that release substance P (SubP). CFTR is an anion channel involved in fluid secretion and mutated in CF; the role of CFTR in secretions stimulated by SubP is unknown. We used optical methods to measure SubP-mediated secretion from human submucosal glands in lung transplant tissue. Glands from control but not CF subjects responded to mucosal chili oil. Similarly, serosal SubP stimulated secretion in more than 60% of control glands but only 4% of CF glands. Secretion triggered by SubP was synergistic with vasoactive intestinal peptide and/or forskolin but not with carbachol; synergy was absent in CF glands. Pig glands demonstrated a nearly 10-fold greater response to SubP. In 10 of 11 control glands isolated by fine dissection, SubP caused cell volume loss, lumen expansion, and mucus flow, but in 3 of 4 CF glands, it induced lumen narrowing. Thus, in CF, the reduced ability of mucosal irritants to stimulate airway gland secretion via SubP may be another factor that predisposes the airways to infections. Jae Young Choi, Monal Khansaheb, Nam Soo Joo, Mauri E. Krouse, Robert C. Robbins, David Weill, Jeffrey J. Wine Hepatic steatosis is present in insulin-resistant obese rodents and is concomitant with active lipogenesis. Hepatic lipogenesis depends on the insulin-induced activation of the transcription factor SREBP-1c. Despite prevailing insulin resistance, SREBP-1c is activated in the livers of genetically and diet-induced obese rodents. Recent studies have reported the presence of an ER stress response in the livers of obese ob/ob mice. To assess whether ER stress promotes SREBP-1c activation and thus contributes to lipogenesis, we overexpressed the chaperone glucose-regulated protein 78 (GRP78) in the livers of ob/ob mice using an adenoviral vector. GRP78 overexpression reduced ER stress markers and inhibited SREBP-1c cleavage and the expression of SREBP-1c and SREBP-2 target genes. Furthermore, hepatic triglyceride and cholesterol contents were reduced, and insulin sensitivity improved, in GRP78-injected mice. These metabolic improvements were likely mediated by restoration of IRS-2 expression and tyrosine phosphorylation. Interestingly, GRP78 overexpression also inhibited insulin-induced SREBP-1c cleavage in cultured primary hepatocytes. These findings demonstrate that GRP78 inhibits both insulin-dependent and ER stress–dependent SREBP-1c proteolytic cleavage and explain the role of ER stress in hepatic steatosis in obese rodents. Hélène L. Kammoun, Hervé Chabanon, Isabelle Hainault, Serge Luquet, Christophe Magnan, Tatsuro Koike, Pascal Ferré, Fabienne Foufelle Overexpression of FGF receptor 3 (FGFR3) is implicated in the development of t(4;14)-positive multiple myeloma. While FGFR3 is frequently overexpressed and/or activated through mutations in bladder cancer, the functional importance of FGFR3 and its potential as a specific therapeutic target in this disease have not been elucidated in vivo. Here we report that inducible knockdown of FGFR3 in human bladder carcinoma cells arrested cell-cycle progression in culture and markedly attenuated tumor progression in xenografted mice. Further, we developed a unique antibody (R3Mab) that inhibited not only WT FGFR3, but also various mutants of the receptor, including disulfide-linked cysteine mutants. Biochemical analysis and 2.1-Å resolution crystallography revealed that R3Mab bound to a specific FGFR3 epitope that simultaneously blocked ligand binding, prevented receptor dimerization, and induced substantial conformational changes in the receptor. R3Mab exerted potent antitumor activity against bladder carcinoma and t(4;14)-positive multiple myeloma xenografts in mice by antagonizing FGFR3 signaling and eliciting antibody-dependent cell-mediated cytotoxicity (ADCC). These studies provide in vivo evidence demonstrating an oncogenic role of FGFR3 in bladder cancer and support antibody-based targeting of FGFR3 in hematologic and epithelial cancers driven by WT or mutant FGFR3. Jing Qing, Xiangnan Du, Yongmei Chen, Pamela Chan, Hao Li, Ping Wu, Scot Marsters, Scott Stawicki, Janet Tien, Klara Totpal, Sarajane Ross, Susanna Stinson, David Dornan, Dorothy French, Qian-Rena Wang, Jean-Philippe Stephan, Yan Wu, Christian Wiesmann, Avi Ashkenazi Ca2+/calmodulin–dependent kinase II (CaMKII) has been implicated in cardiac hypertrophy and heart failure. We generated mice in which the predominant cardiac isoform, CaMKIIδ, was genetically deleted (KO mice), and found that these mice showed no gross baseline changes in ventricular structure or function. In WT and KO mice, transverse aortic constriction (TAC) induced comparable increases in relative heart weight, cell size, HDAC5 phosphorylation, and hypertrophic gene expression. Strikingly, while KO mice showed preserved hypertrophy after 6-week TAC, CaMKIIδ deficiency significantly ameliorated phenotypic changes associated with the transition to heart failure, such as chamber dilation, ventricular dysfunction, lung edema, cardiac fibrosis, and apoptosis. The ratio of IP3R2 to ryanodine receptor 2 (RyR2) and the fraction of RyR2 phosphorylated at the CaMKII site increased significantly during development of heart failure in WT mice, but not KO mice, and this was associated with enhanced Ca2+ spark frequency only in WT mice. We suggest that CaMKIIδ contributes to cardiac decompensation by enhancing RyR2-mediated sarcoplasmic reticulum Ca2+ leak and that attenuating CaMKIIδ activation can limit the progression to heart failure. Haiyun Ling, Tong Zhang, Laetitia Pereira, Christopher Kable Means, Hongqiang Cheng, Yusu Gu, Nancy D. Dalton, Kirk L. Peterson, Ju Chen, Donald Bers, Joan Heller Brown The accumulation of certain species of bacteria in the intestine is involved in both tissue homeostasis and immune-mediated pathologies. The host mechanisms involved in controlling intestinal colonization with commensal bacteria are poorly understood. We observed that under specific pathogen–free or germ-free conditions, intragastric administration of Pseudomonas aeruginosa, E. coli, Staphylococcus aureus, or Lactobacillus gasseri resulted in increased colonization of the small intestine and bacterial translocation in mice lacking Cd1d, an MHC class I–like molecule, compared with WT mice. In contrast, activation of Cd1d-restricted T cells (NKT cells) with α-galactosylceramide caused diminished intestinal colonization with the same bacterial strains. We also found prominent differences in the composition of intestinal microbiota, including increased adherent bacteria, in Cd1d–/– mice in comparison to WT mice under specific pathogen–free conditions. Germ-free Cd1d–/– mice exhibited a defect in Paneth cell granule ultrastructure and ability to degranulate after bacterial colonization. In vitro, NKT cells were shown to induce the release of lysozyme from intestinal crypts. Together, these data support a role for Cd1d in regulating intestinal colonization through mechanisms that include the control of Paneth cell function. Edward E.S. Nieuwenhuis, Tetsuya Matsumoto, Dicky Lindenbergh, Rob Willemsen, Arthur Kaser, Ytje Simons-Oosterhuis, Sylvia Brugman, Keizo Yamaguchi, Hiroki Ishikawa, Yuji Aiba, Yasuhiro Koga, Janneke N. Samsom, Kenshiro Oshima, Mami Kikuchi, Johanna C. Escher, Masahira Hattori, Andrew B. Onderdonk, Richard S. Blumberg NK cells use a variety of receptors to detect abnormal cells, including tumors and their metastases. However, in the case of melanoma, it remains to be determined what specific molecular interactions are involved and whether NK cells control metastatic progression and/or the route of dissemination. Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1), two emerging NK cell receptors key for cancer cell recognition, but not NK group 2 member D (NKG2D). Compared with cell lines derived from metastases taken from other anatomical sites, LN metastases were more susceptible to NK cell lysis and preferentially targeted by adoptively transferred NK cells in a xenogeneic model of cell therapy. In mice, DNAM-1 and NCR ligands were also found on spontaneous melanomas and melanoma cell lines. Interference with DNAM-1 and NCRs by antibody blockade or genetic disruption reduced killing of melanoma cells. Taken together, these results show that DNAM-1 and NCRs are critical for NK cell–mediated innate immunity to melanoma cells and provide a background to design NK cell–based immunotherapeutic strategies against melanoma and possibly other tumors. Tadepally Lakshmikanth, Shannon Burke, Talib Hassan Ali, Silvia Kimpfler, Francesco Ursini, Loredana Ruggeri, Marusca Capanni, Viktor Umansky, Annette Paschen, Antje Sucker, Daniela Pende, Veronika Groh, Roberto Biassoni, Petter Höglund, Masashi Kato, Kazuko Shibuya, Dirk Schadendorf, Andrea Anichini, Soldano Ferrone, Andrea Velardi, Klas Kärre, Akira Shibuya, Ennio Carbone, Francesco Colucci Heritable and acquired diseases of podocytes can result in focal and segmental glomerulosclerosis (FSGS). We modeled FSGS by passively transferring mouse podocyte–specific sheep Abs into BALB/c mice. BALB/c mice deficient in the key complement regulator, decay-accelerating factor (DAF), but not WT or CD59-deficient BALB/c mice developed histological and ultrastructural features of FSGS, marked albuminuria, periglomerular monocytic and T cell inflammation, and enhanced T cell reactivity to sheep IgG. All of these findings, which are characteristic of FSGS, were substantially reduced by depleting CD4+ T cells from Daf–/– mice. Furthermore, WT kidneys transplanted into Daf–/– recipients and kidneys of DAF-sufficient but T cell–deficient Balb/cnu/nu mice reconstituted with Daf–/– T cells developed FSGS. In contrast, DAF-deficient kidneys in WT hosts and Balb/cnu/nu mice reconstituted with DAF-sufficient T cells did not develop FSGS. Thus, we have described what we believe to be a novel mouse model of FSGS attributable to DAF-deficient T cell immune responses. These findings add to growing evidence that complement-derived signals shape T cell responses, since T cells that recognize sheep Abs bound to podocytes can lead to cellular injury and development of FSGS. Lihua Bao, Mark Haas, Jeffrey Pippin, Ying Wang, Takashi Miwa, Anthony Chang, Andrew W. Minto, Miglena Petkova, Guilin Qiao, Wen-Chao Song, Charles E. Alpers, Jian Zhang, Stuart J. Shankland, Richard J. Quigg The mechanism of mitochondrial damage, a key contributor to renal tubular cell death during acute kidney injury, remains largely unknown. Here, we have demonstrated a striking morphological change of mitochondria in experimental models of renal ischemia/reperfusion and cisplatin-induced nephrotoxicity. This change contributed to mitochondrial outer membrane permeabilization, release of apoptogenic factors, and consequent apoptosis. Following either ATP depletion or cisplatin treatment of rat renal tubular cells, mitochondrial fragmentation was observed prior to cytochrome c release and apoptosis. This mitochondrial fragmentation was inhibited by Bcl2 but not by caspase inhibitors. Dynamin-related protein 1 (Drp1), a critical mitochondrial fission protein, translocated to mitochondria early during tubular cell injury, and both siRNA knockdown of Drp1 and expression of a dominant-negative Drp1 attenuated mitochondrial fragmentation, cytochrome c release, caspase activation, and apoptosis. Further in vivo analysis revealed that mitochondrial fragmentation also occurred in proximal tubular cells in mice during renal ischemia/reperfusion and cisplatin-induced nephrotoxicity. Notably, both tubular cell apoptosis and acute kidney injury were attenuated by mdivi-1, a newly identified pharmacological inhibitor of Drp1. This study demonstrates a rapid regulation of mitochondrial dynamics during acute kidney injury and identifies mitochondrial fragmentation as what we believe to be a novel mechanism contributing to mitochondrial damage and apoptosis in vivo in mouse models of disease. Craig Brooks, Qingqing Wei, Sung-Gyu Cho, Zheng Dong The progression of kidney disease to renal failure correlates with infiltration of mononuclear immune cells into the tubulointerstitium. These infiltrates contain macrophages, DCs, and T cells, but the role of each cell type in disease progression is unclear. To investigate the underlying immune mechanisms, we generated transgenic mice that selectively expressed the model antigens ovalbumin and hen egg lysozyme in glomerular podocytes (NOH mice). Coinjection of ovalbumin-specific transgenic CD8+ CTLs and CD4+ Th cells into NOH mice resulted in periglomerular mononuclear infiltrates and inflammation of parietal epithelial cells, similar to lesions frequently observed in human chronic glomerulonephritis. Repetitive T cell injections aggravated infiltration and caused progression to structural and functional kidney damage after 4 weeks. Mechanistic analysis revealed that DCs in renal lymph nodes constitutively cross-presented ovalbumin and activated CTLs. These CTLs released further ovalbumin for CTL activation in the lymph nodes and for simultaneous presentation to Th cells by distinct DC subsets residing in the kidney tubulointerstitium. Crosstalk between tubulointerstitial DCs and Th cells resulted in intrarenal cytokine and chemokine production and in recruitment of more CTLs, monocyte-derived DCs, and macrophages. The importance of DCs was established by the fact that DC depletion rapidly resolved established kidney immunopathology. These findings demonstrate that glomerular antigen–specific CTLs and Th cells can jointly induce renal immunopathology and identify kidney DCs as a mechanistic link between glomerular injury and the progression of kidney disease. Felix Heymann, Catherine Meyer-Schwesinger, Emma E. Hamilton-Williams, Linda Hammerich, Ulf Panzer, Sylvia Kaden, Susan E. Quaggin, Jürgen Floege, Hermann-Josef Gröne, Christian Kurts Idiopathic pulmonary fibrosis (IPF) can lead to the development of secondary pulmonary hypertension (PH) and ultimately death. Despite this known association, the precise mechanism of disease remains unknown. Using a rat model of IPF, we explored the role of the proangiogenic and antiapoptotic growth factor VEGF in the vascular remodeling that underlies PH. In this model, adenoviral delivery of active TGF-β1 induces pulmonary arterial remodeling, loss of the microvasculature in fibrotic areas, and increased pulmonary arterial pressure (PAP). Immunohistochemistry and mRNA analysis revealed decreased levels of VEGF and its receptor, which were inversely correlated with PAP and endothelial cell apoptosis in both the micro- and macrovasculature. Treatment of IPF rats with adenoviral delivery of VEGF resulted in reduced endothelial apoptosis, increased vascularization, and improved PAP due to reduced remodeling but worsened PF. These data show that experimental pulmonary fibrosis (PF) leads to loss of the microvasculature through increased apoptosis and to remodeling of the pulmonary arteries, with both processes resulting in PH. As administration of VEGF ameliorated the PH in this model but concomitantly aggravated the fibrogenic process, VEGF-based therapies should be used with caution. Laszlo Farkas, Daniela Farkas, Kjetil Ask, Antje Möller, Jack Gauldie, Peter Margetts, Mark Inman, Martin Kolb Nicotinic acid is one of the most effective agents for both lowering triglycerides and raising HDL. However, the side effect of cutaneous flushing severely limits patient compliance. As nicotinic acid stimulates the GPCR GPR109A and Gi/Go proteins, here we dissected the roles of G proteins and the adaptor proteins, β-arrestins, in nicotinic acid–induced signaling and physiological responses. In a human cell line–based signaling assay, nicotinic acid stimulation led to pertussis toxin–sensitive lowering of cAMP, recruitment of β-arrestins to the cell membrane, an activating conformational change in β-arrestin, and β-arrestin–dependent signaling to ERK MAPK. In addition, we found that nicotinic acid promoted the binding of β-arrestin1 to activated cytosolic phospholipase A2 as well as β-arrestin1–dependent activation of cytosolic phospholipase A2 and release of arachidonate, the precursor of prostaglandin D2 and the vasodilator responsible for the flushing response. Moreover, β-arrestin1–null mice displayed reduced cutaneous flushing in response to nicotinic acid, although the improvement in serum free fatty acid levels was similar to that observed in wild-type mice. These data suggest that the adverse side effect of cutaneous flushing is mediated by β-arrestin1, but lowering of serum free fatty acid levels is not. Furthermore, G protein–biased ligands that activate GPR109A in a β-arrestin–independent fashion may represent an improved therapeutic option for the treatment of dyslipidemia. Robert W. Walters, Arun K. Shukla, Jeffrey J. Kovacs, Jonathan D. Violin, Scott M. DeWire, Christopher M. Lam, J. Ruthie Chen, Michael J. Muehlbauer, Erin J. Whalen, Robert J. Lefkowitz Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults. Kimber L. Stanhope, Jean Marc Schwarz, Nancy L. Keim, Steven C. Griffen, Andrew A. Bremer, James L. Graham, Bonnie Hatcher, Chad L. Cox, Artem Dyachenko, Wei Zhang, John P. McGahan, Anthony Seibert, Ronald M. Krauss, Sally Chiu, Ernst J. Schaefer, Masumi Ai, Seiko Otokozawa, Katsuyuki Nakajima, Takamitsu Nakano, Carine Beysen, Marc K. Hellerstein, Lars Berglund, Peter J. Havel Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis. Meng-Yun Chou, Linda Fogelstrand, Karsten Hartvigsen, Lotte F. Hansen, Douglas Woelkers, Peter X. Shaw, Jeomil Choi, Thomas Perkmann, Fredrik Bäckhed, Yury I. Miller, Sohvi Hörkkö, Maripat Corr, Joseph L. Witztum, Christoph J. Binder The fatal immune dysregulation that sometimes follows EBV infection in boys has been linked to mutations in two X chromosome–encoded genes, SLAM-associated protein (SAP) and X-linked inhibitor of apoptosis (XIAP). In this study we describe 2 girls from a consanguineous Turkish family who died after developing severe immune dysregulation and therapy-resistant EBV-positive B cell proliferation following EBV infection. SNP array–based genome-wide linkage analysis revealed IL-2–inducible T cell kinase (ITK) as a candidate gene for this immunodeficiency syndrome. Both girls harbored a homozygous missense mutation that led to substitution of a highly conserved residue (R335W) in the SH2 domain of ITK. Characteristics of ITK deficiency in mouse models, such as absence of NKT cells and high levels of eomesodermin in CD8+ cells, were seen in either one or both of the girls. Two lines of evidence suggested that R335W caused instability of the ITK protein. First, in silico modeling of the mutant protein predicted destabilization of the SH2 domain. Additionally, Western blot analysis revealed that, unlike wild-type ITK, the R335W mutant was nearly undetectable when expressed in 293 T cells. Our results suggest that ITK deficiency causes what we believe to be a novel immunodeficiency syndrome that leads to a fatal inadequate immune response to EBV. Because ITK deficiency resembles EBV-associated lymphoproliferative disorders in boys, we suggest that this molecular cause should be considered during diagnosis and treatment. Kirsten Huck, Oliver Feyen, Tim Niehues, Franz Rüschendorf, Norbert Hübner, Hans-Jürgen Laws, Tanja Telieps, Stefan Knapp, Hans-Heinrich Wacker, Alfons Meindl, Hassan Jumaa, Arndt Borkhardt Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3–dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers. María Salazar, Arkaitz Carracedo, Íñigo J. Salanueva, Sonia Hernández-Tiedra, Mar Lorente, Ainara Egia, Patricia Vázquez, Cristina Blázquez, Sofía Torres, Stephane García, Jonathan Nowak, Gian María Fimia, Mauro Piacentini, Francesco Cecconi, Pier Paolo Pandolfi, Luis González-Feria, Juan L. Iovanna, Manuel Guzmán, Patricia Boya, Guillermo Velasco The uptake of lipoproteins by macrophages is a critical step in the development of atherosclerotic lesions. Cultured monocyte-derived macrophages take up large amounts of native LDL by receptor-independent fluid-phase pinocytosis, either constitutively or in response to specific activating stimuli, depending on the macrophage phenotype. We therefore sought to determine whether fluid-phase pinocytosis occurs in vivo in macrophages in atherosclerotic lesions. We demonstrated that fluorescent pegylated nanoparticles similar in size to LDL (specifically nontargeted Qtracker quantum dot and AngioSPARK nanoparticles) can serve as models of LDL uptake by fluid-phase pinocytosis in cultured human monocyte–derived macrophages and mouse bone marrow–derived macrophages. Using fluorescence microscopy, we showed that atherosclerosis-prone Apoe-knockout mice injected with these nanoparticles displayed massive accumulation of the nanoparticles within CD68+ macrophages, including lipid-containing foam cells, in atherosclerotic lesions in the aortic arch. Similar results were obtained when atherosclerotic mouse aortas were cultured with nanoparticles in vitro. These results show that macrophages within atherosclerotic lesions can take up LDL-sized nanoparticles by fluid-phase pinocytosis and indicate that fluid-phase pinocytosis of LDL is a mechanism for macrophage foam cell formation in vivo. Chiara Buono, Joshua J. Anzinger, Marcelo Amar, Howard S. Kruth Our aging society is confronted with a dramatic increase of patients suffering from tauopathies, which include Alzheimer disease and certain frontotemporal dementias. These disorders are characterized by typical neuropathological lesions including hyperphosphorylation and subsequent aggregation of TAU protein and neuronal cell death. Currently, no mechanism-based cures are available. We generated fluorescently labeled TAU transgenic zebrafish, which rapidly recapitulated key pathological features of tauopathies, including phosphorylation and conformational changes of human TAU protein, tangle formation, neuronal and behavioral disturbances, and cell death. Due to their optical transparency and small size, zebrafish larvae are well suited for both in vivo imaging and drug development. TAU-induced neuronal cell death was imaged by time-lapse microscopy in vivo. Furthermore, we used this zebrafish model to identify compounds targeting the TAU kinase glycogen synthase kinase 3β (GSK3β). We identified a newly developed highly active GSK3β inhibitor, AR-534, by rational drug design. AR-534 reduced TAU phosphorylation in TAU transgenic zebrafish. This transgenic zebrafish model may become a valuable tool for further studies of the neuropathology of dementia. Dominik Paquet, Ratan Bhat, Astrid Sydow, Eva-Maria Mandelkow, Stefan Berg, Sven Hellberg, Johanna Fälting, Martin Distel, Reinhard W. Köster, Bettina Schmid, Christian Haass Zhenglin Yang, Yali Chen, Concepcion Lillo, Jeremy Chien, Zhengya Yu, Michel Michaelides, Martin Klein, Kim A. Howes, Yang Li, Yuuki Kaminoh, Haoyu Chen, Chao Zhao, Yuhong Chen, Youssef Tawfik Al-Sheikh, Goutam Karan, Denis Corbeil, Pascal Escher, Shin Kamaya, Chunmei Li, Samantha Johnson, Jeanne M. Frederick, Yu Zhao, Changguan Wang, D. Joshua Cameron, Wieland B. Huttner, Daniel F. Schorderet, Frances L. Munier, Anthony T. Moore, David G. Birch, Wolfgang Baehr, David M. Hunt, David S. Williams, Kang Zhang Justin J. Taylor, Connie M. Krawczyk, Markus Mohrs, Edward J. Pearce

Nasus Build Guide by SlanderCage Not Updated For Current Season Not Updated For Current Season Nasus is my favorite champ, and he has good synergy with most other champs. Nasus can be played as a full tank with MASSIVE damage potential, or as many other varieties, and still out damage other tanks and even some carries. My guide for Nasus is centered around making him as tanky as possible while giving some nice damage items to boost his ferocity in team fights. I have always believed the key to being a tank is showing the enemy team how much of a threat you really are, and Nasus can do that easily. His Siphoning Strike combined with Wither can absolutely devastate AS/AD carries, and his ultimate Fury of the Sands provides a 15 second AOE that makes him do more damage the more time he spends around enemies. His E, Spirit Fire, helps drop armor on tanks so they become less of a threat. This is my first guide, so read through it before judging. Thanks. :) Masteries for this build are mainly tanky, with a point in utility to lower the cooldown on Flash and the reduced casting time for Teleport. Everything else is about giving Nasus solid defensive posture while maintaining his offensive capabilities by lowering cooldowns so Siphoning Strike and Wither can be used quicker. Runes are centered around early game dominance, and a good base to build tanky up through mid and late game. Greater Glyph of Magic Resist This gives Nasus great MR early on to combat ganking AP champs or resist his opponent top lane. Also a good base to build more MR on. Greater Seal of Armor Again, this is for that early game resistance to damage so you can stay in lane longer. Greater Mark of Attack Speed Some question my use of these runes, but 15% attack speed gives you more use out of your passive Soul Eater. If a fight with an enemy champ leaves you drained, these will ensure you can stay in lane with Nasus' awesome sustain. Greater Quintessence of Endurance More health the merrier! You gain a total of 4.5% max health starting, which helps scale your Atma's Impaler later. Also gives you more survivability in lane, which is what you want as solo top. Also, this gives you some nice bonuses when buying health items like Giant's Belt. I personally believe this is a must on every champ. Can either be your #1 escape tool, or allow you to get that last kill to score an Ace. Very useful early to mid game, letting you drop in on undefended turrets or set up a gank on another lane. I mostly use it after I have pushed my lane to the enemy turret, then recall back to base for health/mana and items. Helps you get back in lane when you really need to, and gives an allied Teemo with his Noxious Trap the ability to let you go pretty much anywhere on the map. Other viable spells- Only to be taken if your team lacks CC. Chances are someone else will grab it though, so only take this when needed, as Nasus already has an exhaust with his Wither. True damage, healing handicap, what's not to like? Chances are your carries have this already, so don't worry about taking it unless you really want to. Useful, ESPECIALLY against heavy CC teams. Can help in team fights, letting you tank enemy champ's CC abilities like Lux's Light Binding or Sion's Cryptic Gaze, then use Cleanse to surprise the enemy. Also great for pursuer's who slow/stun you to get that extra kill. A viable alternate to Flash, but has its limits. This one is personal preference. To be honest, pretty much useless on Nasus. He's mana hungry throughout early game, but his mana problem is helped by Sheen, and made irrelevant with Frozen Heart. Never take this. We have Sight Wards for this. An awesome spell, allowing you to turn a fight around in lane, or provide much needed health to your team in fights. Take this if you'd rather be a more supportive tank. Can be useful, but acts much the same way as Fury of the Sands. Once you hit level 6 this spell becomes almost useless, though it will give you an edge in 1v1s and some team fights. NEVER take this. Sure, coming back instantly helps YOU, but does nothing for the team. Your second slot can be put to much better use, so never consider this. Your basic skill sequence will be Q,W,Q,E,R,Q. If an enemy is getting away, chase then Wither as soon as it's available. If you absolutely dominate a 1v1, make sure Siphoning Strike scores you that last hit, so you profit even more from an enemy's demise! Also viable to clean up team fights. Your E, Spirit Fire is good for farming and pushing lanes. Don't be afraid to push a lane quickly so you can help your team out. Your ultimate, Fury of the Sands, can be either a great initiating tool, or an escape mechanism. Popping at max level while you have low health gives you 600 health so you can turn around and fight back or use it as a buffer to escape a pursuing enemy champ. In a team fight, it always helps to make sure Fury of the Sands is off cooldown. This is a great initiation tool, causing damage to all enemies within its effective area. The amount of damage you do to surrounding enemies translates to more damage for you, so don't be afraid to mix it up with the enemy team. Find the closest enemy carry and handicap them with Wither. If you have to choose between an AP carry like Morgana, or an AD like Xin Zhao, prioritize the AD. Wither is Nasus' personal exhaust, and can really put a stop to those fast hitting AD champs. ALWAYS be hitting something with Siphoning Strike. A well farmed Q can lead to a lot of victorious games. That AP carry dropping spell bombs on your team? Not when they get hit with almost 500-650 damage with one Siphoning Strike. This is your bread and butter, and also scales off attack damage, synergizing well with Atma's Impaler. Spirit Fire is great to cast right after Wither. Whatever enemy happens to be sorry enough to be caught on top of it has reduced armor and is continually taking damage. This is amazing to use to in any 1v1 with Nasus, as it allows his Siphoning Strike to absolutely devastate the enemy champ. This has won me 1v1 tank fights on occasion. Pros / Cons -Super tanky late game, and very threatening mid and early game. -His Siphoning Strike can be one of the single most damaging abilities in the game. - Wither=personal exhaust. -Farms really well mid to late game using Spirit Fire. - Fury of the Sands makes you near unstoppable. - Hit /j while waiting for minions to spawn to get some laughs. -His Siphoning Strike is farm dependent, which can take a while to strengthen. -Can be ganked early and shut down before he can shine. -Can be focused down quickly if you get full of yourself. -Has a weak early game, so play defensive while you farm. Playing with Nasus Overview of Abilities Grants Nasus 14/17/20% lifesteal. Great for in-lane sustain. Q, Siphoning Strike- Cooldown- 8/7/6/5/4 per level Mana- 20/25/30/35/40 mana per level Physical Damage- 30/50/70/90/110 per level+100% of your Attack Damage+3 damage for every enemy slain with it. Your bread and butter. Any Nasus with an un-farmed Q is a useless champ indeed. Cooldown-15/14/13/12/11 per level Slow over 5 seconds from 35% to 47/59/71/83/95% over 5 seconds. The best single target slow in the game. This is Exhaust on crack. Not only does it last twice as long, the effects become STRONGER throughout the duration, giving you plenty of time to catch that fleeing champ, or close the distance on your lane opponent to send him crying back to base. E, Spirit Fire- Cooldown- 12 seconds On cast, this creates an area that does continuous magic damage to any enemy inside. It gains 55/95/135/175/215+60% of AP on its initial burst, with 11/19/27/35/43+12% of AP damage per second while inside it. The total damage is 110/190/270/350/430+120% of AP, giving this ability some hitting power if you build some AP with it. Reduces enemy Armor by 20/25/30/35/40 while inside it, and for 1 second afterwards. This should be used in teamfights either A.) against an enemy tank, especially ones who benefit from Armor( Rammus or Malphite) or B.) against a lone carry which will make your attacks hit that much harder with scaled AD from Siphoning Strike, or your own AD carry. Can also be used to quickly push lanes and help farm Siphoning Strike. R, Fury of the Sands- This is what makes Nasus so amazing. On cast, he gains 300/450/600 health for 15 seconds, becoming a huge embodiment of Anubis.(No lie.) He is surrounded by a sandstorm for the duration, and does continuous DoT, dealing 3/4/5% of enemies max health+0.01% AP to ALL enemies around him, maxing out at 240 damage per second. He also takes 6.375% of damage dealt and converts it to attack damage for the duration. This can be used in many different ways. Destroying the enemy team? Feel free to charge in and pop this as soon as you're in range for Wither. This makes his Siphoning Strike that much more deadly. Also, use it when low on health and want to give that chasing enemy something to think about. If a team fight goes bad, pop this and run to your nearest turret. If an enemy pursues you, Wither them and turn the fight to your advantage. I've caught quite a few over confident players with this, making it an extremely effective baiting tool. Nasus has an awesome amount of strength while supporting teammates in killing enemy champs, and even getting the coveted ''LEGENDARY!" -Provides amazing CC with Wither. Use it on the closest AD/AP Carry entering a team fight to cripple them and ensure a kill. - Siphoning Strike is an amazing farm tool that can one hit minions once farmed enough. If nothing else is going on, farm that Siphoning Strike! -Your Spirit Fire reduces Armor, making it good to use against the enemy tank if he is causing trouble for your team. Also good during a 1v1 with anyone, makes your Siphoning Strike hit that much harder. - Fury of the Sands is a powerful team fight tool. It pretty much acts like Sunfire Cape's passive, but with the added bonus of doing damage based off of enemy health, and granting you bonus AD with damage dealt by it. This will help you survive those really nasty team fights, so use it wisely. All in all, Nasus should focus enemy carries. The amount of damage he does can send those hard hitting AP champs like Morgana or Annie running for the hills, or AD champs like Caitlyn or Olaf wish they had chosen a different role in pre-game. Focus on your Q. It takes practice, but eventually you can learn how to score last hits every time with Siphoning Strike, netting you a TON of late game damage. If you're laning against a lot of poke damage, like Teemo or Ashe, keep your distance and LET yourself get pushed to your turret. Once you have your Wither, the enemy will think twice to run up and poke you, and if they do, pop Wither on them and watch as they lose a ton of health from turret shots. If they run, LET THEM. Push your lane, farm your Siphoning Strike. Being greedy with Nasus gets you killed quick. Wait, bide your time, and jump the enemy solo top when you have a good chance. Nasus is a snowball champ, so letting early kills get away at the expense of your Siphoning Strike is well worth it late game. On the other hand, feel free to play aggressive if you're jungler is doing a good job, but let him pick up the kill by using Wither on the enemy champ as soon as he comes out to gank, and supporting him when necessary. This is when Nasus starts to truly shine. You can pick up some solid kills and good assists by working with your team. By now, your Siphoning Strike should have anywhere between 150-225 extra damage on it from minion kills. (Check by running your mouse icon over the ability symbol in game, and locating the number in blue on the description. If leveled right, your Siphoning Strike should be hitting for almost 500+ damage per hit. If you EVER find an enemy champ isolated from his team, punish him with a Siphoning Strike, Wither, Siphoning Strike combo, using Spirit Fire if you feel you're not doing enough damage. You're also tanky enough to solo Dragon, or steal enemy buffs. Do this for extra gold, and always last hit with Siphoning Strike. At this point, your Siphoning Strike should be at least 250-325 extra damage, meaning you can one shot minions. (Depends on damage, but Caster creeps die with one shot, with maybe an auto attack+your Q to kill them.) Basically, if any minion has damage to it, you can instakill it with Siphoning Strike. If there's a lane that needs pushing, push it only when SAFE ENOUGH TO DO SO. Your Siphoning Strike makes extremely short work of turrets. This also makes Nasus a very effective backdoor champ. In team fights, always focus on the opposing teams heaviest source of damage. Don't be afraid to drop some damage items for more MR and Armor, and become more tanky. Wither should be used to cripple enemy melee champs making bee lines to your own carries, giving them time to put major hurt on them. A good combo is to cast Wither on the enemy tank, followed by Spirit Fire to drop his armor so your own AD carry can do some good damage to him. Don't be afraid to pump a few Siphoning Strike's into him for good measure. In team fights, ALWAYS be at the front. A few hits to save one of your carries is a small price to pay for winning the fight. Remember, against certain champs like Caitlyn, you can intercept attacks like her Ace in the Hole. Losing a teammate to one of those attacks can be devastating to your team as a whole, but presents a small inconvenience to you with a stacked Warmog's Armor/ Force of Nature combo. Always, always, ALWAYS spam Siphoning Strike to maximize your output of damage. You can turn team fights to your advantage early by utilizing this effectively. When Fury of the Sands is active, don't be afraid to mix in with enemy teams. DON'T be afraid to become the focus though. If a team mate like Lux is around, or any champ with a good stun, wait till they launch a few disables, then close in on the chosen target. Initiating with it is also viable, but be careful when doing so. To be a better support for your team, also buy a Sight Ward or Vision Ward or two before heading back to lane. Preventing ganks and knowing where the enemy is wins games. As Nasus tank, your main job is to soak up damage, which is relatively easy with Fury of the Sands, but this also makes you a much bigger target. Initiate carefully. Start off with: Boots of Speed and 3 health potions. Doran's Shield if you feel like you want extra resistance to a top lane AD pick. Cloth Armor and 5 health potions, or 3 health potions and a sight ward.(You have to wait for the 5 extra gold after minions spawn, but it's worth the wait to prevent early ganks.) On your first recall, go for Ninja Tabi, or Mercury's Treads, depending on your lane opponent, or build for what the enemy team has the most strength in. At this time, picking up a part of Trinity Force is a must. I usually go for Phage, but Sheen is good if you find yourself running low on mana. Take Zeal if you need the extra movement/attack speed,and crit chance. Mid Game Items Continue farming so you can get Trinity Force. Expensive, at 4070 gold, but it provides Nasus with everything he needs, including health, attack damage, movement speed, attack speed, crit chance, ability power, and the passive on Sheen which adds 100 magic damage on your first basic attack after you cast an ability.(Stacks with Siphoning Strike) Trinity Force is one item I consider must have on Nasus. Mid Game Armor Choices Mid Game is all about making Nasus resistant to damage. Start off with a Giant's Belt. You'll see why in a second. My top choice for "Armor" is Warmog's Armor. 920 health, 30 health regen, with stacks from minion and champs kills(3.5 health+0.10 health regen per 5 for minions and 35 health+1 health regen per 5 for champs), maxing out at 350 health+10 health regen per 5 when fully stacked. Expensive at 3000 gold, but well worth it if you can get it early on. Your Giant's Belt builds into it. Stacking Armor and MR on top of this can make Nasus an unstoppable force. Which leads to my next part. If enemy AD is giving you trouble here's a few decent Armor choices to help you: 100 Armor, and returns 30% of basic attack damage as magic damage to the champ hitting you. Death to AD champs like Xin Zhao, Caitlyn, and Fiora. 2000 gold. - Glacial Shroud: 45 Armor, 425 mana, and reduces cooldowns by 15%. Good to get your Siphoning Strike out quicker. 1525 gold. Can be built into Frozen Heart. - Sunfire Cape: 45 Armor, 450 health. A passive that deals 40 magic damage a second to any enemy in the immediate area. 2610 gold. - Randuin's Omen: 75 Armor, 350 health, 5% CDR, and a passive 20% chance on being hit to slow the attackers movement speed by 35% for 3 seconds. Its active is what you want though. Upon activation, all enemies within range are slowed by 35% for 2 seconds+0.5 seconds for every 100 Armor and Magic Resist you have. 3075 gold. - Guardian Angel: 68 Armor, 38 Magic Resist. Its passive revives you from death, with 750 health, and 375 mana. A good hybrid item, and one that can definitely turn the tide. Should be your top pick if you can't get Warmog's Armor. 2600 gold. Mid Game Magic Resist Items A lot of the best MR items start off with a Negatron Cloak, so pick this up to give enemy AP less hitting power against you mid game. - Force of Nature: 40 health regen, 76 Magic Resist, +8% Movement Speed. Its passive restores 1.75% of your maximum health per 5 seconds. My top choice for MR, goes great with Warmog's Armor, making your health regen RIDICULOUS. 2610 gold. Other good choices are: - Abyssal Scepter: 70 ability power, 57 Magic Resist. This beefs up your Spirit Fire and Fury of the Sands, on top of providing a useful aura that reduces enemy MR by 20 when in range. Take this if you have an AP heavy team. 2650 gold. - Hexdrinker, building into Maw of Malmortius: Hexdrinker provides you with 25 Attack Damage, 30 Magic Resist, and a passive that shields you from 250 damage after taking magic damage that leaves you at less then 30% health. Building into Maw of Malmortius gives you more Attack Damage(55), Magic Resist(36), and the shield goes up to 400 damage. The added passive on this grants you 1 Attack Damage per 2.5% health missing. Good for when you have to get up close to those melee AP carries like Katarina or Fizz. 3300 gold. - Spirit Visage: A steal for how much it costs, Spirit Visage grants you 250 health, 30 Magic Resist, and 10% CDR. The beauty about this item is that it improves the effectiveness of ALL healing on you, making your passive Soul Eater that much more effective. 1550 gold. - Banshee's Veil: 375 health, 50 Magic Resist, and 375 mana. A passive that blocks one negative enemy spell every 45 seconds. Overall, a crazy good item to build against mixed teams. 2715 gold. Late Game Items Late Game you need to focus on what your teams needs most. If you have plenty of damage, AD or AP, then focus on tank items. If not, pick up the below: - Atma's Impaler: 45 Armor, 18% Crit chance. Adds Attack Damage equal to 1.5% of your maximum health to all your basic attacks. Combined with Crit chance from Trinity Force, this can make you deal insane amounts of damage when you use Siphoning Strike. 2355 gold. - Frozen Mallet: 700 health, 20 Attack Damage, and a nice passive slows enemy movement speed by 40% on hit. Health, Damage, and a form of CC. All things a good Nasus tank needs. 3250 gold. -If you're being outfarmed, or otherwise pushed from your lane, head into the jungle and farm the neutral creeps with your Siphoning Strike. Check with your jungler first though to avoid denying him his resources. -If you keep getting pushed to your turret, an easy way to score hits with Siphoning Strike is to let the turret 2-shot an undamaged creep, then run in and hit with your Q. This makes defending your turret easier early game, and nets you some easy stacks on Siphoning Strike. -Buy a Sight Ward on your first trip back to base, 2 if possible. always plant them on the first bush in the river, and either the tribush in the enemy jungle, or the big bush closest to the enemy tower. -Call for ganks as much as possible when soloing Nasus, especially if you're being out farmed on lane. -Make sure you know it's safe before you start pushing the enemy turret. A well placed Exhuast, or any slow/stun can put an end to your fun. -Make sure you keep an eye on your lane after you drop the first turret. An enemy champ may push and win some extra gold for his team. There you have it. This is my guide to Solo Top Nasus. Please leave comments and don't forget to vote. Criticism is welcome, and I appreciate ONLY positive criticism. Also, don't down vote cause you also have a Nasus guide, as I will not do the same to you, especially if you're guide is a good one, which you can expect me to up-vote if I ever read it. Thanks, and EXCELSIOR!! :D

Innate immunity plays a central role in infection-driven inflammatory conditions, including periodontitis which is one of the most common chronic disorders of infectious origin in humans. However, successful microbial pathogens, such as the periodontopathogen Porphyromonas gingivalis, have evolved mechanisms which proactively manipulate the innate immune response. Subversion of innate immunity may additionally undermine the overall host defense, since the innate immune response plays an instructive role in adaptive immunity. This research proposal has been designed to investigate and elucidate molecular mechanisms whereby P. gingivalis modifies innate immune signaling pathways leading to increased virulence and persistence within the host. Although innate recognition and signaling in response to P. gingivalis is primarily mediated by the Toll-like receptor 2 (TLR2)-centered pattern recognition apparatus, preliminary studies indicate that this periodontal pathogen instigates the association of the chemokine receptor CXCR4 with TLR2 resulting in cross-talk and altered signaling downstream of TLR2. On the basis of additional preliminary evidence, the overall hypothesis is that P. gingivalis, through its cell surface fimbriae, exploits CXCR4 and manipulates TLR2 intracellular signaling in ways that suppress the proinflammatory/antimicrobial pathway but enhance a distinct proadhesive pathway;both of these activities have the potential to increase the survival capacity of the pathogen, thereby prolonging P. gingivalis infection and potentiating its impact on periodontal disease. In vitro immunological approaches using transfected cell lines or primary macrophages will elucidate the mechanistic basis of TLR2/CXCR4 cross-talk, which is hypothesized to involve the cAMP-dependent protein kinase A. Moreover, the biological significance of the putative exploitation of CXCR4 by P. gingivalis will be investigated using a mouse periodontitis model, in which a CXCR4 antagonist (AMD3100) is expected to suppress P. gingivalis virulence. The long-term objective of investigating CXCR4-dependent mechanisms whereby P. gingivalis manipulates TLR2 signaling is to identify effective antagonists for redirecting the innate response to benefit the host. The fight against HIV and AIDS has produced a number of drugs including CXCR4 antagonists, which are available for investigation in other formidable diseases where CXCR4 may play a pathophysiological role. Such CXCR4 antagonists may find therapeutic application in human periodontitis. Periodontitis is one of the most common chronic disorders of infectious origin in humans, and is also associated with systemic diseases such as atherosclerosis. This research proposal presents evidence that the periodontal pathogen P. gingivalis exploits a host receptor, namely CXCR4, for undermining host defense and promoting its virulence. We believe that CXCR4 antagonists may find therapeutic application in human periodontitis and, in this context;we will test a CXCR4 antagonist (AMD3100) for its ability to inhibit P. gingivalis-induced periodontitis in a mouse model. |Lamont, Richard J; Hajishengallis, George (2015) Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol Med 21:172-83| |Hajishengallis, George (2015) Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol 15:30-44| |Mitroulis, Ioannis; Alexaki, Vasileia I; Kourtzelis, Ioannis et al. (2015) Leukocyte integrins: role in leukocyte recruitment and as therapeutic targets in inflammatory disease. Pharmacol Ther 147:123-35| |Choi, E Y; Lim, J-H; Neuwirth, A et al. (2015) Developmental endothelial locus-1 is a homeostatic factor in the central nervous system limiting neuroinflammation and demyelination. Mol Psychiatry 20:880-8| |Hajishengallis, George (2014) Aging and its Impact on Innate Immunity and Inflammation: Implications for Periodontitis. J Oral Biosci 56:30-37| |Maekawa, Tomoki; Krauss, Jennifer L; Abe, Toshiharu et al. (2014) Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host Microbe 15:768-78| |Hajishengallis, E; Hajishengallis, G (2014) Neutrophil homeostasis and periodontal health in children and adults. J Dent Res 93:231-7| |Hajishengallis, G; Sahingur, S E (2014) Novel inflammatory pathways in periodontitis. Adv Dent Res 26:23-9| |Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia et al. (2014) Genetic and intervention studies implicating complement C3 as a major target for the treatment of periodontitis. J Immunol 192:6020-7| |Moutsopoulos, Niki M; Konkel, Joanne; Sarmadi, Mojgan et al. (2014) Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med 6:229ra40| Showing the most recent 10 out of 70 publications

In today's post I am participating with thirteen bloggers under a united theme organized by fellow colleague Ayala Moriel. Please follow the links at the end of this post to travel to the other participants in this blogorama. 1. Juniper Essential Oil I came to the world of aromatherapy via essential oil of Juniper. The story of this journey has been repeated often in classes and lectures over the past fourteen years. I was in the midst of a divorce, my daughter Eve was three at the time and the prospect of single motherhood was terrifying. In an effort to rid myself of the psychological trauma as quickly as possible I decided to do as much inner work as possible. The type of work ranged from massage, kinesiology, rebirthing, working with a psychologist, a vision quest and participating in events with women. A native American sweat lodge with a group of women was one such effort. After the pipe ceremony DeeDee, the friend who had invited me to the sweat, placed four little bottles of essential oil into the center of the circle. She encouraged each of us to anoint ourselves before proceeding to the lodge. I went over and deeply breathed in the aroma from each amber bottle. To my surprise upon inhaling one of the essences I was transported to a vital and fragrant forest where I instantly felt uplifted and fortified. That portal was a bottle of Juniper essential oil. From then on I began to learn as much as I could about essential oils, ultimately resulting in a certificate in Aromatherapy and becoming a tutor the East West School of Herbal and Aromatic Studies. Soon I switched from teaching illustration classes at Art schools to teaching the benefits of Aromatherapy. Eventually that path widened to include Botanical Perfume. 2. In Fiore In the year 2002, approximately, I met several individuals interested in botanical natural perfume which have become dear friends. One of them is colleague and mentor Julie Elliot of InFiore. Although I make my own beauty products there are specific items from Julies line that I adore and save for special occasions, like when I need a comfort scent. My two favorites at the moment are Fleur Vibrante, a Jasmine face balm, and the Rose petal "cleansing face and restorative balm" called Lustra. These are heavenly and created by hand from pure, vital ingredients. 3. California Sage Ever since moving to the Santa Monica Mountains I have developed a fondness for the aroma of the native sages. Many different varieties grace our native garden. I adore how the scent fills the air with their herbal authenticity. Sometimes when we get home at night the scent of sage is the first thing I whiff as I open the car door. I'm looking forward for our plants to get really large so that the fragrance will broadcast throughout the neighborhood and provide food for the honey bees. Sometimes I feel like I could just live on tea with milk and honey, in fact there are days where I will realize I haven't had anything else. One of my favorites is Herbal Chocolate and Roses from the Tea Garden and Herbal Emporioum. Another favorite is Puerh, lately I have been enjoying the one from Numi, normally I pick it up while in Chinatown. My other tea obsessions are Mate from my homeland Argentina, Vanilla bean from Mighty Leaf and a really good cup of Earl Grey. Did you know that Earl Grey tea is flavored with essential oil of Bergamot? 5. Cimbalom & Chaparral® Besides Julies beauty products and my essential oil collection the only other scented items I wear are my own perfumes. The two I most often reach for, especially out of balance, are Cimbalom and Chaparral® in their solid format. I keep both of these in my purse so that I can inhale or put some on whenever the need may arise. 6. The Bath In aromatherapy the essences most often listed as comfort scents include: Sandalwood, Chamomile, Lavender, any essence in the citrus family but particularly Tangerine and Neroli, Frankincense, Rose and Vetiver. One of the things I do routinely to rsetor balance is to have a bath with one of the above mentioned essential oils or a synergy. My favorite is a combination of Patchouli, Ylang Ylang and Tangerine....euphoric, grounding, relaxing and extremely comforting, especially before bed. Many thanks to Ayala for inviting me here today, now please journey on to the blogs of the other participants.... Notes from the Ledge The Non Blonde Perfume in Progress Katie Puckrik Smells A Rose Beyond the Thames I Smell Therefore I Am All I Am A Redhead Images: Enchantment and Sierra ©Greg Spalenka, Lustra ©InFiore, Sage photo, Tea cup on parchment and Cimbalom by Roxana Villa.

I just realized something the other day – that “lovelies” is actually “Love + Lies”! Yikes but Hmm…;) Well, let me assure you that my Love for YOU (my most fabulous and intelligent readers) and for this blog is NOT a LIE! I may not be “IN LOVE” with ya, but I sure as heck love ya and then some lol. Truly! But I think you know that already. Okay, before I get started, I gotta’ tell ya – “Eyez got a BIG one for ya dis week!” On the Agenda I’m hoping some of you had the chance to read my post from yesterday, “Are You “A Tad Bit” Obsessed with Facebook?” The good news is that it’s short – I know you don’t believe me but take my word for it on this one. It also includes a fantastic inforgraphic about Facebook that’s loaded with fun, mind-boggling stats. Oh, and make sure to share your thoughts on how you use Facebook and blah blah blah… Make sure to check back this coming Tuesday as I’ll be asking for your help in choosing a name for my new bi-weekly series :). As some of you know, I did this once before in choosing the name for this roundup and I’m hoping to get the same enthusiastic feedback as I did then. I’ll be listing a few titles that I’m leaning towards and I’d love to get your vote on one of them as well as your 2 cents. Gin Gin, I’m counting on you again! No…not Gin as in alcohol. Jeez! Although I’m sure she likes good wine – but Gin Gin as in Gini Dietrich. Brankica over at Live Your Love has started a new bi-weekly roundup of awesome posts – similar to mine, but quite different. Her “Sweet Sunny Saturday” has its own style and is loaded with useful resources. So make sure to head over there every other Saturday of the month. Last but Certainly Not Least I know I mentioned this in last week’s roundup but it’s just THAT good! My friend and excellent business mind and blogger Michele Welch from New Biz Blogger, has written the eBook of all times! Don’t panic…I’m not asking you to buy it – it’s FREE! The Synergy of Business and Blogging: Top Techniques from 31 Successful Bloggers features 31 of some of the most useful posts from around the blogosphere. Did I mention that one of mine is in there too ;)? So please do yourself a favor and grab a copy! - Establishing business goals - Social networking tips - Link building techniques - Traffic generating strategies - Blogging for business - Keyword research - And tons more! Michele has done a hell of job and I think you’ll find yourself thanking her 31 times after you’ve read it. The Goodies – I Mean Reading Homework! I think I’ve talked – I mean rambled – I mean written – quite enough here! And although I’d love to tell you how frickin’ amazing this week’s roundup is and yadi yadi ya…I’d rather not! Cause if you don’t know that by now then, Pfff… “Without further ado and blah blah,” here are this Sunday’s SuperPosts on all things Social Media, Blogging Tips, SEO, Internet Marketing, Traffic Building, Online Money Making Tools and more. - Is it OK to fake your tweets? by Mark Schaefer, businessesgrow.com The other day a prominent Twitter celebrity was kind enough to re-tweet one of my blog posts. It was not Kim Kardashian. At least that time. Any way, because of his power and influence, my link was promptly re-tweeted by 12 of his followers… - No More Gurus! 10 Great Online Keynotes – by Geoff Livingston, geofflivingston.com Read this Quora post about “interesting speakers on social media.” It features some of the most well known voices touting each other. It was disappointing to see the same old same old, including the usual lack of recommended female speakers (8 out of 41)… - 5 Social Media Lessons From Tim Burton – by Marjorie Clayman, pushinsocial.com Not many people have neutral feelings when it comes to Tim Burton – people either love him or hate him. He’s such a conundrum. He’s so hard to pin down. He’s an elite director, but he certainly looks nothing like James Cameron or Steven Spielberg… - Are You A Small Minded Business? – by Troy Claus, spinsucks.com “All I need to do to take my business to the next level is get a Facebook page and a Twitter account.” That has become the mindset of many SMBs (Small Minded Businesses). Coupled with that mindset is usually the understanding that financial results are instant… - 8 Ways to Collect Enough Blog Post Ideas for the Next 100 Years – by Judy Dunn, bestbloggintipsonline.com Grapes of Wrath author John Steinbeck once said, “Ideas are like rabbits. You get a couple and learn how to handle them, and pretty soon you have a dozen.” He’s right. Successful bloggers are always watching and listening… - 7 Blogging Tips From Top Bloggers – by Amy Porterfield, socialmediaexaminer.com If you’ve been following the boom of social media marketing, you already know blogging is an essential ingredient to any social media strategy. Are you unsure about what to write, when to post, how to grow your subscribers… - Making the Most of a Sticky Post – by Rick LaPoint, internetmarketing.ricklapoint.com WordPress has taken over much of the Web, and for very good reason. WordPress makes it very easy for beginners and non-techies to put up their own website without the expense of paying someone else to do the… well, tech stuff… - 10 Ways to Find TONS of Blogs to Comment On – by Tristan Higbee, bloggingbookshelf.com Earlier this week I wrote about how to get 100 comments on a blog post. The main idea of that post was that if you comment on 100 blogs, some of those bloggers will come back to comment on your blog. You then reply to those comments… - Bloggers on Content Strategy – by Mark, icebluebanana.com There are so many things you need to do to start a successful Internet business that it is often easy for bloggers to forget about their strategy for the content on their site, and off of it. I believe that a solid content strategy is essential for me… - 7 key elements that will put your blog into a total success frenzy – by Adam Paudyal, ideasbubble.com Take a look around the blogosphere; what do you see? Hundreds of blogs sprouting like wild mushrooms on the forest floor; on a daily basis. Some are here to Crush it! Some do not make it or some just blend in with the rest. Those who do make it… - 7 Signs You’re a Hacker & 5 Ways it Can Help Your Blog – by Kiesha Easley, weblogbetter.com You’re probably a hacker, and don’t even know it. The term has developed a negative connotation, so many resist the idea. But let me start by breaking down the word. Webster’s Dictionary defines the term Hacker as… - How To Hack Your Own Blog Without Anyone Noticing. – by Alex Whalley, alexwhalley.com Ever used a butter knife to tighten a screw?’ indeed… Welcome back, I hope you enjoyed the read, and more importantly, now have a better understanding of what we are talking about when we say Hacker. I particularly enjoyed that post… - Are Your Readers Dumb? – by Lisa, thefriendlyblogger.com If you have your blog or website analyzed, either with a free tool, or a professional, you will see some interesting metrics. You will receive a website grade and one of these measurements is readability level. So what is the optimal… - The 15 Best SEO Tips For WordPress in 2011 – by Nicholas Cardot, sitesketch101.com Search engine optimization, or SEO, doesn’t have to be scary. It can be fun and exciting to put these WordPress SEO tips to use and to watch your blog begin receiving targeted visitors from people who are actively searching for exactly… - Top SEO Women of 2011 – by Gabriella Sannino, level343.com 2011 is here, and I know many of you have been trying to get your budgets, online presence and campaigns off the ground. I’d love to tell you it’s easy, but I’d be lying to you. Rather than pour a whole bunch of information out today… - Why Brogan’s Bigger Ear Marketing Is Wrong – by Gini Dietrich, spinsucks.com One of the last people I want to antagonize is Chris Brogan, but I’ve been thinking about this all week so here goes nothing. Dear Chris, You are wrong. Love, Gini. On Monday, Chris had a blog post called “Bigger Ear Marketing for Authors.” In the post he extols… - What You Don’t Know About Your Target Market Is a Lot – by Elizabeth McGee, trafficgenerationcafe.com Who is your target market? That may sound like an obvious question, but you may be surprised to learn that your ideal target market isn’t quite the ten million people surfing the net each and every day like you thought. In reality, your target market… - How To Build A Subscriber List With Mobile Marketing – by Elise Moreau, elisesreview.com Quite surprisingly, I’ve never actually owned a smartphone before in my life. I have a three year-old Samsung cell phone, which has been kicked, dropped, sat on, scratched, and one of the buttons doesn’t even work anymore. I know that it’s time… - Link Building Mastery: Master The Art of Link Building – by Mark Collier, basicblogtips.com Everyone knows link building and backlinks are key components of good search engine rankings and a website or blog that gets traffic from both the search engines and its peers. There are many forms that traffic backlinks manifest themselves in… - 5 Networking, Traffic and Content Truths You Should Know – by Daniel Sharkov, reviewzntips.blogspot.com Bloggers are blogging because they want to get their message heard by an audience, they wouldn’t otherwise have. Getting thousands of people listen to what you have to say is a powerful tool. It’s a fact that a lot of individuals have made fortunes.. - What’s Wrong with My Blog Readers? – by Rick LaPoint, internetmarketing.ricklapoint.com Have you ever been frustrated when your best writing falls flat on it’s pontificating little face? I feel that way at times. The other day I wrote an article I thought was incredibly well-written. It was a treasure trove of insightful… - The Most Powerful Weapon in the World – by Debbi Morello, dannybrown.me After reading Danny’s post and insightful comments on “Could This Be Your Child?”, I got to thinking about the provocative image used with the post and some of the reactions to the image. So, I wanted to speak to the power of images… - Why I Chose MailChimp Over Aweber – by Sire, wassupblog.com Now you’ve all heard about Aweber and how it’s supposed to be the bees knees of auto-responders? Well I decided against it because I just couldn’t see the value in it. These guys are so up themselves they won’t even offer a free trial! Instead you have to pay… [image credit: Statesrrg.com]

Ford Motor Co. is preparing for the risk that higher oil prices and a slowing U.S. economy crimp demand and will cut production as needed to avoid building costly inventories, senior executives said on Tuesday. Speaking to reporters in advance of the Los Angeles Auto Show, Ford Chief Executive Alan Mulally said the economic concerns for Ford included tighter credit markets and a U.S. housing market that could remain weak for another year or two. When you add that together, it's a very concerning environment, Mulally said. But Mulally said Ford would be more disciplined than it has been in the past about cutting production if it sees sales slipping, including the pickup trucks and SUVs that represent the heart of the automaker's current line-up. The business environment has clearly gotten tougher, he said. It's gotten tougher and we want to be ready to move if we need to. Mark Fields, Ford's president for the Americas, said the automaker would be watching sales results every week to keep its inventory levels in balance. Taken together the comments pointed to the prospect of U.S. factory layoffs by Ford at a time when the struggling automaker is on the cusp of clinching a cost-saving, four-year deal with the United Auto Workers union. Ford rivals General Motors Corp. and Chrysler LLC both moved quickly to cut production levels in the wake of their own contract deals with the UAW in recent weeks. Mulally declined to comment on Ford's expectations for an expanded round of worker buyouts and early retirement offers under the automaker's still-pending UAW contract. Ford has been waiting for the deal to be ratified by its roughly 58,000 UAW-represented workers and could brief analysts and investors on the deal as early as Wednesday, he said. Fields said with gas prices on track to approach $4 per gallon in some U.S. cities, consumers were bound to rethink planned purchases of bigger and less fuel-efficient vehicles. I think it will change behavior in a big way, he said. Given the economic situation, Fields said Ford executives were kind of surprised by the relatively stable share of pickup truck sales as a share of total U.S. vehicle sales over the past three to four months. But if sales show signs of slipping, Ford will act quickly to trim production rather than wait for a turnaround as it might have in recent downturns, Fields said. This is a different approach than we've had in the past, said Mulally, who left Boeing Co. to take the top job at Ford just over a year ago. Ford dominates the market for pickup trucks with its F-150 series, but the No. 2 U.S. automaker been struggling in segments such as smaller cars it had neglected in recent years when more profitable truck and SUV sales were booming. Ford's U.S. sales have dropped 13 percent through October compared with the same period a year earlier. Mulally said Ford did not need to bring in a strategic partner or an outside investor to complete its restructuring and return to profitability in 2009. Ford's bigger cost-saving opportunity is to integrate regional operations by sharing development and procurement costs, Mulally said. I think a link-up would be a distraction, Mulally said. The real synergy for Ford is to integrate Ford. The first test of the new global development plans will be a compact car now under development that Fields said would mark a departure from Ford's history of trying to lure entry-level buyers with something cheap and cheerful. Mulally said the goal for Ford was to develop a more balanced vehicle line-up by adding the more fuel-efficient cars and car-based crossovers to round out its truck offering. I think we're getting back to the history of Ford and that is Ford for all, he said. That's what built Ford. (Editing by Louise Ireland)

Follow our progress and participate in cavity prevention events and lectures around the world. Experts at Alliance for a Cavity-Free Future (ACFF) Symposium Call for Collaboration and “Joining Up Existing Evidence” to Promote Successful Caries Prevention and Management Inaugural Symposium marks longer-term partnership between the ACFF and UAE International Dental Conference (AEEDC) Dubai, 18 February 2016 – The Alliance for a Cavity-Free Future (ACFF) held its first annual symposium at the 20th annual UAE International Dental Conference in Dubai (AEEDC) on 2 February 2016. The day-long session – titled “The Fight for a Cavity-Free Future: ‘Joining Up’ the Evidence to Make an Achievable Difference” engaged key thought leaders in robust discussion to not only understand the existing body of evidence regarding the current approach to caries prevention and control, but to determine how to integrate that evidence and identify a clear path towards a cavity-free future for all. The symposium hosted a group of experts across key disciplines, including, nutrition, education and behavior change, cariology, public health, clinical practice, and caries management. “The annual AEEDC meeting brings together leading oral health professionals to address pioneering advancements in oral health research and technology,” said Professor Abdullah R. Al Shammery, Rector of the Riyadh Colleges of Dentistry and Pharmacy in Dubai and Co-Chair of the local North Africa and Middle East ACFF Chapter. “Today’s ACFF Global Symposium is a powerful example of the importance of global collaboration among oral health stakeholders to promote efforts and evidence that address the burden or oral disease on a global scale and, in consequence, drive meaningful change.” A Need for Collaboration: Symposium experts agreed that dental caries is a complex, multifactorial disease that cannot be prevented by the traditional focus on single factors in isolation. Very often, oral health efforts have worked in silos to address pressing issues around oral disease burden. The group suggested that organized collaboration and synergy that effectively “joins up” existing evidence between individual elements of the “Caries Puzzle,” can help fulfil the primary goal of the ACFF, a cavity-free future for all. Symposium experts discussed what specific factors needed to be part of the comprehensive approach and stressed the need for synergy to operationalize the existing evidence: - Sugar: following the new World Health Organizations (WHO) guidance on reducing the amount of free sugars to prevent caries, obesity and diabetes. - Education and behavior change: enabling both patients and health professionals to do the right things at the right time to prevent and control caries. - Cariology: implementing the wealth of evidence about how to control caries, realizing that fluoride is important, but not sufficient, against high sugar challenges. - Public health: responding to the need for advocacy on caries and oral health issues, often neglected in public health policy and practice. - Clinical practice and management: recognizing the clinical evidence to support a preventive approach, as well as adopting a System to deliver caries classification and disease management in dental clinical practice, the International Caries Classification and Management System (ICCMS™). Importantly, experts overwhelmingly agreed that “Joining-up” these pieces of the “Caries Puzzle,” combined with suitable actions from other external stakeholders – including health professions, the public and patients – will allow us to achieve a cavity-free future more rapidly than separate strategies or individual group efforts. A Focus on Sugar A key strategic element for action discussed at the symposium was how best to react to the recently published evidence-based guidelines on sugar consumption issued by the World Health Organization. Implementing these guidelines should impact the health outcomes of patients in terms of caries, obesity and diabetes. However, the group agreed that there exists a gap in policy efforts globally, and discussed ways to strengthen action at the policy level, with potential activities ranging from implementing a sugar tax to expanding sugar information on nutrition labels, noting that similar policies and programs in the tobacco industry have been effective in educating the public and changing behavior. Updating education on the health impact of sugars was also felt to be a priority. “The recently published World Health Organization guidelines on sugar consumption, along with the existing evidence on caries management and prevention, suggest the need to update practice and training protocols so they reflect this new evidence-based nutritional guidance” said Professor Paula Moynihan, Newcastle University, United Kingdom, World Health Organization Collaborating Centre for Nutrition and Oral Health. “Today’s discussions reemphasize the need for clear and meaningful guidance to the dental professional and patients on how to best address the connection between sugar and oral health.” Read the complete Alliance for a Cavity-Free Future (ACFF) Symposium Press Release. Dental And Public Health Leaders From Canada And The United States Target A Cavity-free Future For Children Born In 2026 And Beyond Cavities are the number one chronic disease, despite being preventable and, in the early stages, reversible Chicago, November 3, 2015 – This weekend at the American Public Health Association meeting, leaders in dentistry and public health joined together to launch the Canada-United States Chapter of the Alliance for a Cavity-Free Future (the Alliance). The Alliance aims to facilitate collaboration among the various professional groups who impact oral health with a specific focus on children under the age of six. Read the complete ACFF Canada US Launch Release Alliance for a Cavity-Free Future (ACFF) Celebrates Milestone of Establishing 24 Local Chapters Worldwide BANGKOK, Thailand (September 24, 2015) – The Alliance for a Cavity-Free Future (ACFF) held its sixth annual summit at the FDI World Dental Congress, delivering a report on the Alliance and presenting on issues impacting oral health, including the recently revised World Health Organization (WHO) sugar intake guidelines and the implications of these around caries prevention and management efforts. The ACFF also celebrated the recipients of the inaugural ACFF Champions Award, which commends the work of ACFF Chapters whose programs help drive impactful change in their local communities and beyond. Read the complete ACFF 2015 Summit Press Release. New iCariesCare Digital Applications for Professionals and Patients Aim to Drive Oral Health Behaviour Change Based on International Caries Classification and Management System (ICCMS™) System based on the International Caries Detection and Assessment System (ICDAS) Approach Bangkok, Thailand (September 23, 2015) - The ICDAS Foundation and its Global Collaboratory for Caries Management (GCCM) have announced two new applications that will be provided to dental professionals and patients free of charge to help achieve better early caries prevention by using the International Caries Classification and Management System™ (ICCMS™). The applications were introduced at this week’s FDI Annual World Dental Congress, in Bangkok, Thailand and were made possible by an unrestricted educational grant provided by Colgate. Read the complete ICCMS Press Release. Russian Alliance Launch Leading Russian dental experts announced the launch of the Russian chapter of the Alliance for a Cavity-Free Future (ACFF) on September 28, 2014.The meeting was hosted by the Russian Dental Association – a member of the World Dental Federation (FDI) – that recognizes the important role of the international health initiative. The launch of the Russian chapter gathered 27 of the country’s top experts in dentistry from 17 major dental universities and the Russian Dental Hygienists Association. The meeting was led by Professor Nigel Pitts, ACFF Chair, Vladimir Sadovsky, the RDA President Vladimir Sadovsky, and Valery Leontiev, the RDA Vice-President and member of the Russian Academy of Sciences. Vladimir Sadovsky stressed the urgency of addressing the caries problem in Russia, noting that “without the proper prevention the dental caries incidence in Russia will continue to grow exponentially.” The Alliance members proclaimed their commitment on working on educational programs and long-term programs of caries prevention to be supported and implemented by the dental schools and the professional associations. Experts also agreed that it is important that the local Alliance activities should not only reach the professional community, but it should also involve children and parents through local education programs. Attendees signed the ACFF Declaration at the close of the meeting to celebrate joining the Alliance for a Cavity-Free Future. Joining the Alliance, Russian dental experts will implement the “new” approach to caries as a continuum, which is preventable and even reversible at the early stage using comprehensive caries prevention and management practices. South African ACFF Chapter The South African chapter of the Alliance for a Cavity-Free Future launched on June 25, 2014 in Cape Town, South Africa, with over 60 dental and public health experts in attendance. The meeting was facilitated by Prof Sue Naidoo – Deputy Dean of Research at the University of Western Cape and the panel represented experts from all five dental schools and all three dental organizations in South Africa. In addition, the attendees received a lecture from Professor Nigel Pitts, ACFF Chairman, on global ideas and patterns as well as guide discussions for future plans. This gathering also allowed the South African experts to join together and discuss the importance of optimally managing the growing caries incidence from a South African perspective with the plan to practically combat this disease. There was strong support for the ACFF concept and the potential impact it could play in the future of Oral Health in South Africa. All parties committed to the goals of the Alliance and signed the ACFF declaration. The declaration calls for global collaborative action to challenge health care leaders and stakeholders to learn the importance of caries as a disease continuum, by recognizing that cavities are preventable, and to develop comprehensive programs for prevention and management. Tooth decay is the most common chronic disease on the planet, affecting five billion people, or nearly 80 percent of the world’s population. This disease often restricts activities in school, at work and at home causing millions of school and work hours to be lost each year. Moreover, the psychosocial impact of these diseases often significantly diminishes the quality of life. It is for these reasons that a group of key experts and opinion leaders have joined hands to tackle this debilitating problem. Central Eastern European Chapter Launch Dentistry leaders from Poland, the Czech Republic, Slovakia, Hungary, Romania, Lithuania, Latvia and Estonia signed a regional declaration constituting the Alliance for a Cavity-Free Future Central Eastern European Chapter in which the experts call for national collaborative action to challenge leaders and stakeholders in the community to learn the importance of caries as a disease continuum, recognize that cavities are preventable and caries is reversible in the early stages, and to develop comprehensive programs for prevention and management in the CEE region. Prof. Urszula Kaczmarek, who has been appointed the Chair of the CEE ACFF Chapter, said: “Collaboration is essential for comprehensive prevention and management of caries around the world. We must commit to developing systems on a cross country, national and local level that encourage the public health and clinical communities to work together in addressing the disease. Together we can educate the public and challenge leaders in dentistry and public health to take action. Improvement in the condition of oral health calls for strengthening and continuation of more effective preventive strategies as well as increase of social awareness as far as the meaning of oral health. The latter can be done via motivating oral health promoting programs in accordance with the rule “think global – act local” – added professor Kaczmarek. ACFF Indian Launch At the 67th Indian Dental Conference, dental and public health experts joined together for the launch of Indian chapter of the Alliance for a Cavity-Free Future. The local chapter aims to collaborate with stakeholders across various levels, including government and community leaders, to move towards a cavity-free future. In India, dental caries remains a major oral health problem and is widely prevalent, especially among children. Caries, an early form of cavities, is a prevalent issue in India. On November 20, 2013, experts in dentistry, oral and public health came together to launch the Australian chapter of the global collaboration the Alliance for a Cavity-Free Future. With national representation, the Australian chapter is the ninth chapter to join the global movement towards a cavity-free future. In Australia, as in many countries around the world, tooth decay is still a neglected epidemic, in spite of progress made in prevention and treatment. Government and personal expenditure to repair the damage caused by this disease is very high as is pain and suffering with dental caries being the most common cause of acute preventable hospital admissions (AIHW, Australian Hospital Statistics 2009-10). Wendell Evans – Head of Discipline, Community Oral Health Epidemiology, Faculty of Dentistry, University of Sydney – is chairman of the local chapter which includes 15 leaders in dentistry and oral health who are committed to building upon the work already being done in the prevention of caries. Suggested initiatives include engaging general health and community groups, government leaders, dental councils and dental schools in Australia with the aim of improving oral health through engagement, policy changes, and teaching curricula. ACFF Greek Chapter Launch The Hellenic Chapter of the Alliance for a Cavity-Free Future launched in December 2013, aiming at taking initiatives and action in order to contribute to the decrease of caries in the country. The Hellenic Chapter of ACFF has partnered with the Greek Dental Association, the Hellenic Society of Pediatric Dentistry and other representatives of the dental community. In the frame of implementing practices for the improvement of oral health in Greece, ACFF is developing and implementing actions both at the level of proposals for the improvement of the policies on oral care, as well as at the level of the education of population on caries prevention. Towards this direction, Prof. Konstantinos Oulis, co-chair of the ACFF chapter, announced the development and implementation of an “Experiential Learning” educational program on oral health for kindergarten children. This program will be initiated in September 2014, and it’s the first time that such an action at such a degree is implemented for kindergarten children in the country. On October 25, 2013, the Malaysian chapter of the Alliance for a Cavity-Free Future successfully launched. The local ACFF Chairperson, Professor Rahimah Kadir, will lead chapter members in the charge to move towards a cavity-free future. The chapter aims to secure public endorsement while also engaging key public health stakeholders such as the Ministry of Health and the Deans’ Dental Council. With full support from major outlets such as Dental Practice News (DPN), the Malaysian chapter is off to a strong start. DPN has explicitly expressed that initiatives such as the Alliance for a Cavity-Free Future deserve the support of the overall dental healthcare community in the Malaysian region. The Malaysian chapter proudly presented their chapter goals and reviewed the activities they plan to implement this year. One of the activities the chapter plans to initiate is a public health awareness program to promote the importance of proper oral hygiene and educate consumers on dental caries. Through this initiative, the Malaysian chapter will tap into local TV talk shows, radio shows, newspapers (online and print) to promote the oral health program. They also plan to leverage Oral Health Month and promote activities on oral hygiene during this time. Turkish Alliance Launch The Turkish Chapter of the Alliance for a Cavity-Free Future launched at the FDI World Dental Congress in Istanbul on August 26, 2013. Dental experts who attended the launch ceremony included Professor Nigel Pitts, ACFF Chairman, Dr. Oya Aktören and Dr. Esra Yıldız, Co-Chairs of ACFF Turkey Chapter, Dr.Taner Yücel, President of Turkish Dental Association, and Dr. Kanuni Keklik, President of Department of Public Health Services/Ministry of Health. Local Experts Panel members, representatives from the Turkish Dental Association and Departments of Pediatric Dentistry/Restorative Dentistry/Public Health and Colgate-Palmolive Company were also in attendance. Members of the Turkish Chapter signed the Alliance Declaration endorsing the importance of joining the fight against caries. Following the Turkish Alliance launch in August 2013, educational and awareness-raising activities have launched. For example, the regional ICDAS training that brought together 19 KTLs from different countries in AEA division. The ultimate goal of this training was to engage academia as the ambassadors in their schools for the integration of this new tool into their curricula. Eventually, this will raise awareness among the young dental professionals who will in turn raise the awareness with the public in their practice and through their outreach programs. Turkey, as many other countries, has significant problems regarding oral and dental health. Statistics reveal that approximately 70% of 6-year-old children throughout the country have dental caries and related problems and approximately 50% of people aged over 65 have lost most of their teeth. European Alliance Launch On July 22, 2013, the Alliance for a Cavity-Free Future announced the launch of a new European Chapter, to bring together experts in dentistry and public health to create a collaborative focus for the implementation of key changes in dental health practices across Europe. The launch of the European Chapter is the sixth chapter of the global Alliance for a Cavity-Free Future, which began in September 2010. The European Chapter of the Alliance for a Cavity-Free Future is chaired by Professor Nigel Pitts, Director of the Dental Innovation and Translation Centre (ITC) at King’s College London Dental Institute, London, UK, and Professor Svante Twetman, Professor of Cariology at the Faculty of Health Sciences, University of Copenhagen, Denmark. Professors Pitts and Twetman were joined by Professors Andreas Schulte, Klaus Pieper and Kenneth Eaton at a meeting in London to define the goals of the new European Chapter and sign a statement of intent, pledging their commitment to improving dental health practices across Europe. In Europe, tooth decay remains a major problem, especially in Eastern Europe and in socio-economically deprived groups. 1 Many Europeans still do not follow recommended oral hygiene practices, such as using fluoride-containing toothpaste, mouthwashes, inter-dental cleaning and getting regular dental check-ups. Different countries across Europe will be joining the European Chapter of the Alliance for a Cavity-Free Future by implementing local specific initiatives throughout 2013 and 2014. To see a video of Professor Nigel Pitts and Professor Svante Twetman talking about the European Chapter of the Alliance for a Cavity-Free Future and the dental caries landscape in Europe, please visit www.youtube.com/ACFFEurope For further information about dental caries, please visit EU_Chapter_Caries_Fact Sheet.pdf. For more information about the Alliance, please visit www.AllianceForACavityFreeFuture.org 1. Facts and Figures – The State of Oral health in Europe (2012). Available at http://www.oralhealthplatform.eu/sites/default/files/field/document/Factsheet_oral health in Europe_2012_0.pdf [Last accessed June 2013] Central American ACFF Chapter Launch In June 2013, the Central American ACFF chapter was launched with the goal to motivate and engage key players in oral health prevention. Through key partnerships with stakeholders such as the Ministry of Health, the local chapter is paving the way to a Cavity-Free Future. ACFF China Chapter Commits to Stopping Caries Now for a Cavity-Free Future in China Cavities are preventable and in the early stages reversible. On September 13, 2012, national leaders in dentistry and public health joined together and launched the China Chapter of the Alliance for a Cavity-Free Future. Professor Deyu Hu and Profesor Junqi Lin are the co-chairman of ACFF China chapter. Tooth decay is the most common chronic disease on the planet, According to the Survey of Chinese Oral Epidemiology, 85 percent Chinese adults suffer from cavities while 90 percent of them never turn to a dental management or consultation. Deyu Hu, Professor and Chairman of Preventive Dentistry, West China College of Stomatology, Sichuan University, pointed out that 80-97 percent of Chinese have dental problems of varied degrees. “The level of resources and intervention from both a public health and clinical perspective is inconsistent around the world,” said Professor Xing Wang, Chairman of CSA “This means that millions are suffering from a problem we know how to stop. Caries deserves greater attention in order to elevate it as an important health issue.” The ACFF China chapter calls for national collaborative action to challenge leaders and other regional and local stakeholders to learn the importance of caries as a disease continuum, by recognizing that cavities are preventable and in the early stages reversible, and to develop comprehensive programs for prevention and management. The goal of china chapter is 0 cavity after 2026 in China. Venezuela Alliance Launch On April 11, 2012, members of the local dental community joined together to celebrate the launch of the Venezuelan chapter of the Alliance for a Cavity-Free Future; the launch took place at the Aesthetic & Restorative Dentistry Congress in Caracas, Venezuela. Given that the majority of the Venezuelan population has dental problems and oral health diseases, including cavities, more collaborative efforts from the dental and public health community are especially important. In fact, statistics from the most recent Venezuelan health census show that 96% of individuals report having cavities. In an effort to tackle this issue head on, Chairman of the newly launched chapter, Dr. Ana Maria Acevedo, proudly kicked-off the inauguration. With more than 500 attendees present for the launch ceremony, officials from the Board of Health (including BoH Coordinator Dr. Ana K Elorza), Board of Education, National Dentists Association, Venezuelan Dental Schools Association and the Congress Board of Directors were on hand to sign a declaration formalizing the formation of the Venezuelan Alliance Chapter and endorsing the importance of the Alliance in taking action against caries. The launch of the Venezuelan Chapter is the fifth chapter of the global Alliance for a Cavity-Free Future which launched globally in September 2010. Following the launch, the Venezuelan chapter plans develop a series of tactics to permeate dental school curriculums, including a report on the Caries Curricula to the National Faculties Association. Brazilian Alliance Launch At the CIOSP-International Dental Congress Sao Paulo on January 29, 2012 in São Paulo, Brazil, members from the local dental community gathered to launch the Brazilian chapter of the Alliance for a Cavity-Free Future. The launch of the Brazilian chapter is the third chapter of the global Alliance for a Cavity-Free Future, which began in September 2010 and is dedicated to creating a global movement towards a cavity-free future for all age groups. With more than 150 attendees present for the launch ceremony, influential leaders of the local dental community – including Dr. Gilberto Pucca Jr., National Dental Health Coordinator for the Brazilian Ministry of Health – and officials from the São Paulo Dental Association and Brazilian Dental Association were on hand to sign a declaration, formalizing the formation of the Brazilian Alliance Chapter and endorsing the importance of the Alliance in taking action against caries. Led by Head Professor in Pediatric Dentistry at the School of Dentistry at the University of São Paulo, Dr. Marcelo Bönecker, the Brazilian Alliance is looking forward to building on the commitment from leaders of dental organizations, government leaders, dental councils and dental schools in Brazil to change the future of caries and work towards a cavity-free future for all. Specific goals will be set in the coming months. Mexican Alliance Launch On September 16, 2011, worldwide leaders in dentistry and public health gathered at the FDI World Dental Congress in Mexico City to kick-off the Mexican chapter of the Alliance. Following the launch of the first Alliance chapter in Colombia in May 2010, the Mexican chapter of the Alliance is joining the global movement towards a cavity-free future in order to build upon the work already being done on the issue of caries by dental and public health professionals in Mexico. In Mexico alone, tooth decay affects 90 percent of the population, impacting not only the population’s oral health, but also the overall well-being and quality of life of Mexicans, according to the Mexican National Health Program. Led by Dr. Heriberto Vera, former Chief Dental Officer for Mexico and the Chairman of the Mexican Alliance Chapter, key influencers in oral health and public health from Mexico showed their support for a new approach to caries and signed a declaration committing to the goals of the Alliance. Participants included Dr. Jaime Edelson Tishman, President of the Mexican Dental Association and Dr. Agustín López, Executive Secretary of the Mexican Society of Health. In addition to launching the Mexican chapter at FDI, the Alliance for a Cavity-Free Future unveiled a free website for individuals and families that provides information about caries and resources to help prevent and manage early cavities. On the website, individuals and families, who are committed to stopping early cavities, can learn about caries and download a checklist to help assess their current oral health habits. After completing the items on the checklist, individuals and families receive a Certificate of Completion, demonstrating their commitment to oral health. To access the website, please visit www.AllianceForACavityFreeFuture.org or www.alianzaporunfuturolibredecaries.org for a Spanish version. Colombia Alliance Launch On May 15, 2011, Colombia became the first country to launch a local chapter of the Alliance with an event that took place at the Annual Research Meeting of the Colombian Association of Dental Schools (AFCO). Like many other countries across the globe, caries is a significant problem in Colombia, with estimates that six in ten Colombians have suffered tooth decay before turning five years old. In fact, statistics presented at the launch event indicated that 57.2 per cent of children in urban areas and 68 per cent of children in the countryside have suffered from tooth decay. In order to support action in Colombia, several renowned experts from key academic institutions, as well as the Colombian Association of Dental Schools (AFCO) and a representative from Colgate-Palmolive Colombia signed a declaration indication their support for the goals of the Alliance. The Colombia chapter has indicated that it will focus on two action fronts -- academic and community. On the academic front, the Colombian Alliance will be leading a workshop with all dental school members of the Colombian Association of Dental School (ACFO) next September in order to review state of Cariology in the different dental school curriculums. Their goal is to develop a proposal that reaches consensus around dental caries teaching, prevention and management. On the community front, the Colombian Alliance has already identified three intervention sites and is currently working on the design and development of a research protocol that will evaluate the integrated actions directed to the community. The aim is to start on field work by the second quarter of next year. As part of the launch of the Colombian Alliance, a Spanish version of the Alliance site was also launched; the site can be accessed at http://www.alianzaporunfuturolibredecaries.org and offers evidence-based tools and strategies to support materials for local action.

- About this Journal · - Abstracting and Indexing · - Aims and Scope · - Annual Issues · - Article Processing Charges · - Articles in Press · - Author Guidelines · - Bibliographic Information · - Citations to this Journal · - Contact Information · - Editorial Board · - Editorial Workflow · - Free eTOC Alerts · - Publication Ethics · - Reviewers Acknowledgment · - Submit a Manuscript · - Subscription Information · - Table of Contents Journal of Robotics Volume 2012 (2012), Article ID 401613, 14 pages Medical Robots: Current Systems and Research Directions Department of Engineering Technology and Industrial Distribution, Texas A&M University, 3367 TAMU, College Station, TX 77843, USA Received 10 March 2012; Revised 19 June 2012; Accepted 6 July 2012 Academic Editor: Farrokh Janabi-Sharifi Copyright © 2012 Ryan A. Beasley. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. First used medically in 1985, robots now make an impact in laparoscopy, neurosurgery, orthopedic surgery, emergency response, and various other medical disciplines. This paper provides a review of medical robot history and surveys the capabilities of current medical robot systems, primarily focusing on commercially available systems while covering a few prominent research projects. By examining robotic systems across time and disciplines, trends are discernible that imply future capabilities of medical robots, for example, increased usage of intraoperative images, improved robot arm design, and haptic feedback to guide the surgeon. Medical robotics is causing a paradigm shift in therapy. The most widespread surgical robot, Intuitive Surgical’s da Vinci system, has been discussed in over 4,000 peer-reviewed publications, was cleared by the United States’ Food and Drug Administration (FDA) for multiple categories of operations, and was used in 80% of radical prostatectomies performed in the U.S. for 2008, just nine years after the system went on the market [1–3]. The rapid growth in medical robotics is driven by a combination of technological improvements (motors, materials, and control theory), advances in medical imaging (higher resolutions, magnetic resonance imaging, and 3D ultrasound), and an increase in surgeon/patient acceptance of both laparoscopic procedures and robotic assistance. New uses for medical robots are created regularly, as in the initial stages of any technology-driven revolution. In 1979, the Robot Institute of America, an industrial trade group, defined a robot as “a reprogrammable, multifunctional manipulator designed to move materials, parts, tools, or other specialized devices through various programmed motions for the performance of a variety of tasks.” Such a definition leaves out tools with a single task (e.g., stapler), anything that cannot move (e.g., image analysis algorithms), and nonprogrammable mechanisms (e.g., purely manual laparoscopic tools). As a result, robots are generally indicated for tasks requiring programmable motions, particularly where those motions should be quick, strong, precise, accurate, untiring, and/or via complex articulations. The downsides generally include high expense, space needs, and extensive user training requirements. The greatest impact of medical robots has been in surgeries, both radiosurgery and tissue manipulation in the operating room, which are improved by precise and accurate motions of the necessary tools. Through robot assistance, surgical outcomes can be improved, patient trauma can be reduced, and hospital stays can be shortened, though the effects of robot assistance on long-term results are still under investigation. Medical robots have been reviewed in various papers since the 1990s [4–7]. Many such reviews are domain-specific, for example, focusing on surgical robots, urological robots, spine robots, and so forth [8–13]. For an overview of the basic science behind medical robots (e.g., kinematics, degrees of freedom, ergonomics, and telesurgery) along with a discussion of urologic robotic systems, see Challacombe and Stoianovici . Similarly focused on surgery, Kenngott et al. provide a recent Medline metareview on the outcomes of laparoscopic robot-assisted surgeries (urologic, gynecologic, and abdominal) , while Gomes covers market drivers and roadblocks , and Okamura et al. explore big picture issues like societal drivers, quantitative diagnosis, and system adaptation/learning . The most recent coverage of medical robots across various domains was by Najarian et al. and the articles collected by Rosen et al. [18, 19]. This paper provides an overview of the impact of robots in multiple medical domains. This work builds on top of the aforementioned papers by providing an updated review of various robotic systems, covering system improvements (technical and regulatory) and changes in manufacturers due to corporate buyouts. Furthermore, to the author’s knowledge this work covers more breadth in the medical domains benefiting from robot assistance than any other single paper, and thus provides a big picture view of how robots are improving the medical field. Though primarily focused on commercially available medical robotic systems and the history that describes their evolution, this paper also covers multiple next-generation systems and discusses their potential impacts on the future of the medical field. Brain surgery involves accessing a buried target surrounded by delicate tissue, a task that benefits from the ability for robots to make precise and accurate motions based on medical images [18, 20, 21]. Thus, the first published account investigating the use of a robot in human surgery was in 1985 for brain biopsy using a computed tomography (CT) image and a stereotactic frame . In that work, an industrial robot defined the trajectory for a biopsy by keeping the probe oriented toward the biopsy target even as the surgeon manipulated the approach. This orientation was determined by registering a preoperative CT with the robot via fiducials on a stereotactic frame attached to the patient’s skull. That project was discontinued after the robot company was bought out, due to safety concerns of the new owning company, which specified that the robot arm (54 kg and capable of making 0.5 m/s movements) was only designed to operate when separated by a barrier from people. Then in 1991, the Minerva robot (University of Lausanne, Switzerland) was designed to direct tools into the brain under real-time CT guidance. Real-time image guidance allows tracking of targets even as the brain tissue swells, sags, or shifts due to the operation. Minerva was discontinued in 1993 due to the limitation of single-dimensional incursions and its need for real-time CT . The currently available neurosurgery robots exhibit a purpose similar to historical systems, namely, image-guided positioning/orientation of cannulae or other tools (Figure 1). The NeuroMate (by Renishaw, previously by Integrated Surgical Systems, previously by Innovative Medical Machines International) has a Conformité Européenne (CE) mark and is currently used in the process for FDA clearance (the previous generation was granted FDA clearance in 1997) . In addition to biopsy, the system is marketed for deep brain stimulation, stereotactic electroencephalography, transcranial magnetic stimulation, radiosurgery, and neuroendoscopy. Li et al. report in-use accuracy as submillimeter for a frame-based configuration, the same level of application accuracy as bone-screw markers with infrared tracking, and an accuracy of 1.95 mm for the frameless configuration . Another robotic system, Pathfinder (Prosurgics, formerly Armstrong Healthcare Ltd.), has been cleared by the FDA for neurosurgery (2004) . Using the system, the surgeon specifies a target and trajectory on a pre-operative medical image, and the robot guides the instrument into position with submillimeter accuracy . Reported uses of the system include guiding needles for biopsy and guiding drills to make burr holes . Renaissance (Mazor Robotics, the first generation system was named SpineAssist) has FDA clearance (2011) and CE mark for spinal surgery, and a CE mark for brain operations (2011) . The device consists of a robot the size of a soda can that mounts directly onto the spine and provides tool guidance based on planning software for various procedures including deformity corrections, biopsies, minimally invasive surgeries, and electrode placement procedures. Renaissance includes an add-on for existing fluoroscopy C-arms that provides 3D images for intraoperative verification of implant placement. Studies show increased implant accuracy and provide evidence that the Renaissance/SpineAssist may allow significantly more implants to be placed percutaneously . The expected benefit of robot assistance in orthopedics is accurate and precise bone resection [31, 32]. Through good bone resection, robotic systems (Figure 2) can improve alignment of implant with bone and increase the contact area between implant and bone, both of which may improve functional outcomes and implant longevity . Orthopedic robots have so far targeted the hip and knee for replacements or resurfacing (the exception being the Renaissance system in Section 2 and its use on the spine). Initial systems required the bones to be fixed in place, and all systems use bone screws or pins to localize the surgical site. The initial robot assistance for orthopedics came via Robodoc (Curexo Technology Corp, originally by Integrated Surgical Systems), first used in 1992 for total hip replacement [5, 33]. Robodoc has received a CE mark (1996), and FDA clearance for total hip replacement (1998) and total knee replacement (2009) . The robot is used in conjunction with OrthoDoc, a surgical planner, with which the surgeon plans bone milling is based on preoperative CT. During the procedure, the patient’s leg is clamped to the robot’s pedestal, and a second clamp locates the femoral head to automatically halt the robot if the leg moves. The Robodoc then performs the milling automatically based on the surgical plan. Many initial attempts in surgical robotics involved such autonomous motions, which generated concerns about patient and doctor safety. To address those concerns, Robodoc has force sensing on all axes, as well as a six-axis force sensor at the wrist . The force sensing is used for safety monitoring, to allow the surgeon to manually direct the robot arm and to vary the velocity of tool motion as a function of the forces experienced during the milling operation. Though no longer for sale, CASPAR (Computer Assisted Surgical Planning and Robotics) was another robotic system for knee and hip surgery, introduced in 1997 by OrtoMaquet, acquired by Getinge in 2000, acquired and discontinued by Universal Robot Systems (URS) in 2001. The robot was a direct competitor to Robodoc. It automatically performed bone drilling from a preoperative plan based on CT data. In 2008, the RIO robotic arm (MAKO Surgical Corp, previous generation called the Tactile Guidance System) was released and received FDA clearance. The RIO is used for implantation of medial and lateral unicondylar knee components, as well as for patellofemoral arthroplasty [36, 37]. As part of the trend away from autonomous robot motions, both the RIO and the surgeon simultaneously hold the surgical tool, with which the surgeon moves about the surgical site. The arm is designed to be low friction and low inertia, so that the surgeon can easily move the tool, backdriving the arm’s joint motors in the process . The arm’s purpose is to act as a haptic device during the milling procedure, resisting motions outside of the planned cutting envelope by pushing back on the surgeon’s hand. Unlike other orthopedic systems, the RIO does not require the bone to be fixed in place, instead relying on a camera system to track bone pins and tools intraoperatively and instantaneously registering the planned cutting envelope to the patient in the operating room. With this configuration, the system has promise for use as a surgical training tool. Further reducing robotic influence on the cutting tool, the iBlock (Praxim Inc., an Orthopaedic Synergy Inc. company, previous generation the Praxiteles, FDA clearance 2010) is an automated cutting guide for total knee replacement . The iBlock is mounted directly to the bone, preventing any relative motion between the robot and the bone and aligns a cutting guide that the surgeon uses to manually perform planar cuts based on a preoperative plan. Koulalis et al. report reduced surgical time and increased cut accuracy compared with freehand navigation of cutting blocks . The Navio PFS (Blue Belt Technologies, CE mark 2012) does not require a CT scan for unicondylar knee replacement, instead it uses intraoperative planning [40, 41]. The drill tool is tracked during the procedure, and the drill bit is retracted when it would leave the planned cutting volume. Limited information is available on the system due to its recent development. The Stanmore Sculptor (Stanmore Implants, previous generation the Acrobot Sculptor by Acrobot Company Ltd.) is a synergistic system similar to the RIO, with active constraints to keep the surgeon in the planned workspace . The company’s “Savile Row” system tailors a personalized unicondylar knee implant to the patient, incorporates the 3D model of that implant into the surgical planning interface, and uses active constraints with the Stanmore Sculptor to ensure proper preparation of the bone surface. The system does not currently have FDA clearance, but has been in use in Europe since 2004. 4. General Laparoscopy Prior to the 1980s, surgical procedures were performed through sizable incisions through which the surgeon could directly access the surgical site. In the late 1980s, camera technology had improved sufficiently for laparoscopy (a.k.a. minimally invasive surgery), in which one or more small incisions are used to access the surgical site with tools and camera . Laparoscopy significantly reduces patient trauma in comparison with traditional “open” procedures, thereby reducing morbidity and length of hospital stay, but at the cost of increased complexity of the surgical task. Compared with open surgery, in laparoscopy the surgeon’s feedback from the surgical site is impaired (reduced visibility and cannot manually palpate the tissue) and tool control is reduced (“mirror-image” motions due to fulcrum effect and loss of degrees of freedom in tool orientation) [16, 44, 45]. Robot assistance for soft-tissue surgery was first done in 1988 using an industrial robot to actively remove soft tissue during transurethral resection of the prostate . As with neurosurgery, the researchers deemed use of an industrial robot in the operating room to be unsafe. The experience provided the impetus for a research system, Probot, with the same purpose . Commercial robotic systems for laparoscopy started with Computer Motion’s Aesop (discontinued, FDA clearance 1993) for holding endoscopes . Aesop was clamped to the surgical table or to a cart, and either moved the endoscope under voice control or allowed the endoscope to be manually positioned. In 1995, Computer Motion combined two tool-holding robot arms with Aesop to create the Zeus system (discontinued, FDA clearance 2001) . The Zeus’s tool arms were teleoperated, following motions the surgeon made with instrument controls (a.k.a. “master” arms or joysticks) at the surgeon console. Technically, the Zeus is not a robot because it does not follow programmable motions, but rather is a remote computer-assisted telemanipulator with interactive robotic arms. To improve precision in tool motion, the Zeus filters out hand tremor, and can scale large hand motions by the surgeon down to short and precise motions by the tool. As described by Marescaux et al., the Zeus was used in the Lindbergh Operation, the first surgery was (cholecystectomy) performed with the surgeon and patient being separated by a distance of several thousand kilometers . 4.2. da Vinci Meanwhile, Intuitive Surgical Inc. was developing the da Vinci (initial FDA clearance 1995, Figure 3(a)). Like the Zeus, the da Vinci is a teleoperated system, wherein the surgeon manipulates instrument controls at a console and the robot arms follow those motions with motion scaling and tremor reduction. Also like the Zeus, the da Vinci was initially offered with three arms to hold two tools and an endoscope, which are mounted to a single bedside cart. The da Vinci system provides several technical enhancements over the Zeus. The grasper tools have two degrees of freedom inside the patient, the EndoWrist (Figure 3(b)), an enhanced articulation that increases the ease of suturing and other complex manipulations. The console puts increased emphasis on surgeon ergonomics and incorporates a separate video screen for each eye to display 3D video from the 3D endoscope. The motions of the surgeon’s hands are mapped to motions of the operational ends of the tools, providing a more intuitive control than the “mirror-image” laparoscopic mapping. In 2003, Intuitive Surgical began selling a fourth arm for the da Vinci, and Intuitive Surgical and Computer Motion were merged (discontinuing the Zeus). The da Vinci system is the only surgical robot with over a thousand systems installed worldwide and has been sold in four models so far: Standard (1999), S (2006), Si (2009), and Si-e (2010) [50, 51]. The S model increased the image resolution, redesigned the patient-side manipulators to enable multiquadrant access, and shortened setup time. The Si model further improved the visual resolution, refined the instrument controllers, and increased the ergonomics and ease for the surgeon to provide input to the system. The Si-e model is a 3-arm system that is fully upgradeable to the Si model. Continuing the da Vinci focus on improved visualization, the Firefly Fluorescence Imaging add-on product combines fluorescent dye and a special endoscope to identify vasculature beneath the tissue surface. The da Vinci was initially cleared for general laparoscopy, became commonly used for radical prostatectomy, and is now cleared by the FDA for various procedures [52, 53]. Even so, as with most or even all robotic systems, long-term benefits continue to be uncertain [15, 54]. The enhanced endoscopic visualization and increased tool articulation are commonly considered improvements, but detractors point out the system’s expense (between $1 M and $2.3 M), the reduced patient access due to the amount of space the arms take over/around the patient, and the significant amount of training necessary for the best outcomes [55, 56]. To address this last point, the Si model also allows dual console use for training and collaboration, in which both consoles get the same images and can cooperatively control the instruments . Additionally, the da Vinci Skills Simulator is an add-on case that can be used with an Si or Si-e console to practice operations in a virtual environment . In an attempt to further reduce patient trauma, surgeons are exploring Single-Port Access (SPA), LaparoEndoscopic Single-Site surgery (LESS), and Natural Orifice Transluminal Endoscopic Surgery (NOTES) [59, 60]. To meet this need, Intuitive Surgical has recently developed the Single-Site platform for the da Vinci Si model. The Single-Site platform passes two semirigid tools and the endoscope through a single multichannel port, reducing the number of incisions but preventing EndoWrist articulation . The FreeHand robot (Freehand 2010 Ltd., previously Freehand Surgical, previously Prosurgics, the previous generation was called EndoAssist, FDA clearance and CE mark 2009) is a next-generation endoscope holder. The arm (Figure 3(c)) is more compact, easier to setup, and cheaper than its predecessor. Furthermore, endoscope motion is controlled by gentle head motions by the surgeon, which are tracked with an optical system. 4.4. Telelap ALF-X SOFAR S.p.A has developed Telelap ALF-X (CE mark 2011, Figure 3(d)), a four-armed surgical robotic system, to compete with the da Vinci . The system uses eyetracking to control the endoscopic view and to enable activation of the various instruments. Compared to the da Vinci, the system moves the base of the manipulators away from the bed (about 80 cm) and has a realistic tactile-sensing capability due to a patented approach to measure tip/tissue forces from outside the patient, with a sensitivity of 35 grams. The system has been used in animal trials demonstrating a significant reduction in the time for cholecystectomy compared with a “conventional telesurgical system” . Noncatheter percutaneous procedures employ needles, cannulae, and probes for biopsy, drainage, drug delivery, and tumor destruction. During the procedure, accurate targeting can be reduced by soft tissue displacements that occur due to patient breathing, changes in posture, or tissue forces exerted during the insertion. Two options to guide a needle to its target are tissue modeling for needle steering and three-dimensional intraoperative imaging . Unfortunately, tissue modeling is excessively complex . So following the latter approach, InnoMotion (Synthes Inc., previously by Innomedic GmbH, CE mark 2005) is a robot arm designed to operate within a CT or magnetic resonance imaging (MRI) machine [65–67]. For MRI-compatibility, the arm (Figure 4(a)) is pneumatically actuated and joint sensing is via MRI-compatible encoders. 6. Steerable Catheters Vascular catheterization is used to diagnose and treat various cardiac and vasculature diseases, including direct pressure measurements, biopsy, ablation for atrial fibrillation, and angioplasty for obstructed blood vessels [68–70]. The catheter is inserted into a blood vessel and the portion external to the patient is manipulated to move the catheter tip to the surgical site, while fluoroscopy provides image guidance. Due to the supporting tissue, catheters only require three degrees of freedom, typically: tip flexion, tip rotation, and insertion depth. Possible benefits of robot-steered catheters are shorter procedures, reduced forces exerted on the vasculature by the catheter tip, increased accuracy in catheter positioning, and teleoperation (reducing exposure of the physician to radiation) . The Sensei X (Hansen Medical, FDA clearance and CE mark 2007, previous generation the Sensei, Figure 4(c)) uses two steerable sheaths, one inside the other, to create a tight bend radius [72–74]. The sheaths are steered via a remotely operated system of pulleys. IntelliSense force sensing allows constant estimation of the contact forces by gently pulsing the catheter a short distance in and out of the steerable inner sheath and measuring forces at the proximal end of the catheter. These forces are communicated visually as well as through a vibratory feedback to the surgeon’s hand on the “3D joystick”. Corindus’s CorPath 200 is a direct competitor with the Sensei X, but is not yet commercially available. The Niobe (Stereotaxis, CE mark 2008, FDA clearance 2009) is a remote magnetic navigation system, in which a magnetic field is used to guide the catheter tip . The magnetic field is generated by two permanent magnets contained in housings on either side of a fluoroscopy table (Figure 4(b)). The surgeon manipulates a joystick to specify the desired orientation of the catheter tip, causing the orientations of the magnets to vary under computer-control, and thereby controlling the magnetic field. A second joystick controls advancement/retraction of the catheter. Chun et al. report significant improvements in surgical outcomes due to advances in the design of magnetically guided catheters . Radiosurgery is a treatment (not a surgery), in which focused beams of ionizing radiation are directed at the patient, primarily to treat tumors [77, 78]. By directing the beam through the tumor at various orientations, high-dose radiation is delivered to the tumor while the surrounding tissue receives significantly less radiation. Prior to real-time tissue tracking, radiosurgery was practically limited to treating the brain using stereotactic frames mounted to the skull with bone screws. Now that real-time tissue tracking is feasible, systems are commercially available. The CyberKnife (Accuray Inc., FDA cleared 1999, Figure 5(a)) is a frameless radiosurgery system consisting of a robotic arm holding a linear accelerator, a six degree of freedom robotic patient table called the RoboCouch, and an X-ray imaging system that can take real-time images in two orthogonal orientations simultaneously [79, 80]. The two simultaneous, intraoperative X-ray images are not sufficient to provide good definition of the tumor, but are used to register a high-definition preoperative CT image. The robotic arm can then provide the preplanned radiation dosage with a wide range of orientations. For targets that move during treatment (e.g., due to breathing), the optional synchrony system can optically track the tissue surface, correlate the motion of the tissue surface to the motion of radio-opaque fiducials inserted near the target, and thus continuously predict target motion . The intraoperative tracking obviates the need for a stereotactic frame, reducing patient trauma and making it practical to fractionate the dosage over longer time periods. The Novalis with TrueBeam STx (BrainLab Inc. and Varian Medical Systems, previously Novalis and Trilogy, initial FDA clearance 2000, Figure 5(b)) is also a frameless system with a linear accelerator, but with micro-multileaf collimators for beam shaping [82–84]. Similar to CyberKnife, intraoperative X-rays are compared with a CT, and skin-mounted fiducials are optically tracked in real-time. The delivery system also includes cone beam CT. The patient is moved into position on top of a six degree of freedom robotic couch. The major differences between Cyberknife and Novalis are that the Cyberknife radiation source has more degrees of freedom to be oriented around the patient while the Novalis can shape the radiation beam and claim reduced out-of-field dosage [85, 86]. 8. Emergency Response Few medical robot systems are suitable for use outside of the operating room, despite significant research funding on medical devices for disaster response and battlefield medicine. Typical goals for such research include improved extraction of patients from dangerous environments, rapid diagnosis of injuries, and semiautonomous delivery of life-saving interventions. Current Emergency Response robots are little more than single-motor systems, but those systems can be controlled by health monitors to minimize the necessary attention by Emergency Responders. Such a feedback control makes it more likely that such systems will be autonomous, for example, automated external defibrillators. The AutoPulse Plus (ZOLL Medical Corp., previously by Revivant) is an automated, portable device that combines the functions of the AutoPulse (FDA clearance 2008, Figure 6(a)) cardiopulmonary resuscitation device and the E Series monitor/defibrillator (FDA clearance 2010) [87, 88]. Consisting of a half-backboard containing a battery-powered motor that actuates a chest band, the AutoPulse rhythmically tightens the band to perform chest compressions. The tightness of the band during compressions is a function of the patient’s resting chest size, to adjust for interpatient variability. Meanwhile, the E Series monitor/defibrillator measures the rate and depth of chest compressions in real time and filters cardiopulmonary resuscitation artifacts from the electrocardiogram signal. If combined with an automatic battery-powered ventilator, for example, the SAVe (AutoMedx Inc., FDA clearance 2007), basic cardiopulmonary emergency response treatments could be automated while on battery power. The LS-1 “suitcase intensive care unit” (Integrated Medical Systems Inc., previous generation called MedEx 1000, previous generation called LSTAT, FDA clearance 2008, Figure 6(b)) takes an inclusive approach to portable life support . The system contains a ventilator with oxygen and carbon dioxide monitoring, electrocardiogram, invasive and noninvasive blood pressure monitoring, fluid/drug infusion pumps, temperature sensing, and blood oxygen level measurement. The LS-1 is battery powered and can be powered by facility or vehicular electrical sources. The system is FDA-cleared for remote control of its diagnostic and therapeutic capabilities. 9. Prosthetics and Exoskeletons Microprocessor-controlled prosthetics have been available since 1993, specifically the Intelligent Prosthesis knee (Chas. A. Blatchford & Sons, Ltd.). Several microprocessor-controlled prosthetics exist today, predominantly for knee prosthetics, hand prosthetics, and exoskeletons. For example, one current generation knee prosthetic is the C-leg (Otto Bock, FDA clearance 1999, CE mark) which is designed to automatically adjust the swing phase dynamics and improve stability during the stance phase by controlling knee flexion . An example of hand prosthetic is the i-limb ultrahand (Touch Bionics, previous version i-limb hand, FDA clearance and CE mark), the first commercially available hand prosthesis with five individually powered digits, controlled via myoelectric signals generated by muscles in the remaining portion of the patient’s limb . For wheelchair users, the ReWalk (Argo Medical Technologies, FDA clearance 2011, CE mark 2010) is one walking assistance exoskeleton that allows users to stand, walk, and climb stairs and is controlled with a wrist-mounted remote and a posture detection sensor . Significant research on exoskeletons is ongoing, such as the research on upper-limb exoskeletons by Rosen and Perry . For further information in the area of prosthetics and exoskeletons see the works by Kazerooni and Bogue . 10. Assistive and Rehabilitation Systems Assistive robotic systems are designed to allow people with disabilities more autonomy, and they cover a wide range of everyday tasks. In 1992, Handy 1 (Rehab Robotics, Ltd.) became the first commercial assistive robot ; it interacts with different trays for tasks such as eating, shaving, and painting, and it is controlled by a single switch input to select the desired action. One task-specific system is the Neater Eater (Neater Solutions Ltd.), a modular device that scoops food from a plate to a person’s mouth, and can be controlled manually or via head or foot switches. More general systems rely on arms with many degrees of freedom, such as Exact Dynamics’ iARM, a robotic arm with a two-fingered grasper, that attaches to electric wheelchairs and can be controlled via keypad, joystick, or single button. Rehabilitation systems can be similar to assistive systems, but are designed to facilitate recovery by delivering therapy and measuring the patient’s progress, often following a stroke . The Mobility System (Myomo, Inc.) is a wearable robotic device that moves the patient’s arm in response to his/her muscle signals, thus creating feedback to facilitate muscle reeducation. The InMotion (Interactive Motion Technologies, based on the MIT-MANUS research platform) is a robotic arm that moves, guides, or perturbs the patient’s arm within a planar workspace, while recording motions, velocities, and forces to evaluate progress . For information on research efforts, see Dallaway et al. for an overview of thirty assistive and rehabilitation systems, such as the MASTER II system that uses a rail-mounted robotic arm to make manually controlled, remote-controlled, or preprogrammed motions for various domestic and office tasks . Difficulties in developing rehabilitation robots and potential future uses are investigated by Ceccarelli . 11. Current Research and Development in Medical Robotics 11.1. RAVEN and MiroSurge Two prominent academic robot-assisted surgical systems are currently used for research into endoscopic telesurgery: RAVEN II and MiroSurge. The RAVEN II (University of Washington and UC Santa Cruz) is a teleoperated laparoscopic system that was designed to maximize surgical performance based on objective clinical measurements [102–104]. The system has two patient-side arms that are cable-driven with 7 degrees of freedom each. The arm kinematics are based on a spherical mechanism such that the tool always passes through a remote center (e.g., the insertion point for minimally invasive surgery). The length and angles of the links were optimized to maximize performance throughout the workspace. The arms are lighter, smaller, and less expensive than current robotic systems for laparoscopy. The instrument controllers are haptic devices, allowing force feedback on the operator’s hands based on tool forces or virtual fixtures (e.g., forbidden regions) defined with respect to patient anatomy (see [105–107] for the impact of haptics on surgery). Teleoperation experiments have been conducted with the RAVEN, including routing the data transmission through an unmanned aircraft. In February 2012, five systems were provided to various other surgical robotics research labs to spur collaboration and further development efforts. In another endoscopic research effort, the German Aerospace Center (DLR) is developing MiroSurge to be highly versatile with respect to the number of surgical domains, arm-mounting locations, number of robots, different control modes (e.g., control of position versus control of force), and the ability to integrate with other technologies . The expectation is for a base robot system to hold specialized instruments, such as DLR’s MICA instrument (which is itself a robotic tool with 3 degrees of freedom and force sensing) . By using a general robotic base to hold a specialized robotic instrument that has its own motors, sensors, and control electronics, the same base system can be specialized for various procedures just by switching the instrument. The base robot, the DLR Miro, masses 10 kg with a 3 kg payload and has serial kinematics that resemble the kinematics of the human arm, with joint ranges and link lengths optimized based on certain medical procedures . Unlike the RAVEN II, the MIRO arm does not have a remote center of motion, and thus must be controlled to direct the instrument through any insertion point, but is more easily able to handle moving insertion points (e.g., through the chest wall during respiration). Titan Medical Inc. is currently developing Amadeus, a four-armed laparoscopic surgical robot system, to compete with Intuitive Surgical’s da Vinci system. The Amadeus uses snakelike multiarticulating arms for improved maneuverability, and the system is being designed to facilitate teleoperation for long-distance surgery. Human trials are planned for late 2013. 11.3. NeuroArm and MrBot At least two renowned research systems are investigating improved MR-compatible robots. The neuroArm (University of Calgary, MacDonald Dettwiler and Associates, IMRIS) is a two-armed, MRI-guided neurosurgical robot actuated via piezoelectric motors [111, 112]. The neuroArm end effectors are equipped with 3 degrees of freedom optical force sensors and are accurate to tens of micrometers. The MrBot (Johns Hopkins University) is a parallel linkage arm designed for MRI-guided access of the prostate gland, actuated by novel pneumatic stepper motors for reduced MR interference . TraumaPod (highly collaborative, led by SRI International) is a semi-autonomous telerobotic surgical system designed to be rapidly deployable . The surgical cell consists of a surgical robot (da Vinci for Phase I testing), Scrub Nurse Subsystem, Tool Rack System, Supply Dispensing System, Patient Imaging System (a movable X-ray tube), predecessor of the aforementioned LS-1 (“suitcase intensive care unit”), and Supervisory Controller System. The TraumaPod has demonstrated successful teleoperation of a bowel closure and shunt placement on a phantom without a human in the surgical cell. That success implies the potential for increased automation in the operating room, though challenges were reported in sterilization, anesthesia, and robustness. The heart has long been a target for surgical robots and various systems continue to investigate how best to treat cardiac diseases, particularly while the heart is beating (e.g., see Section 6) . The HeartLander (HeartLander Surgical) is a minimally invasive robot that uses suction to crawl around the surface of the heart [116, 117]. The system is designed for intrapericardial drug delivery, cell transplantation, epicardial atrial ablation, and other such procedures. 11.6. Robots In Vivo Various groups are expanding and exploring the da Vinci system’s approach to enhance surgery by increasing the dexterity of the tool inside the patient. One such example is the University of Nebraska’s laparoscopic robotic system for research into single-site surgeries . The system has two arms with six degrees of freedom each, and those arms are fully inserted into the abdomen. The expectation is that, by increasing the tool’s dexterity inside the patient, fewer incisions will be needed to insert instruments because multiple tools/arms can pass through a single incision and then spread out inside the patient. Further, miniaturizing the robotics reduces the difficulty in working with (and around) the system in the operating room. A limited number of animal trials (colon resections) have been performed to demonstrate feasibility. Swallowable capsules take patient trauma reduction to an extreme, but current systems are limited to diagnostic uses. Core temperature measurement has been FDA cleared since 1990, by CorTemp (HQ Inc., formerly HTI Technologies). More recently, capsule endoscopy systems (PillCam by Given Imaging with FDA clearance 2001, and EndoCapsule by Olympus with FDA clearance 2007) consist of a forward-looking wide-angle camera taking regularly timed pictures, a battery, and lights, all contained in a capsule [119, 120]. SmartPill (SmartPill Corp., FDA clearance 2006) utilizes multiple sensors to measure pressure, pH level, gastric emptying time, and bowel emptying time . Sayaka (RF Co Ltd.) is a novel design, not FDA cleared, using a lateral-facing camera that rotates inside the capsule to image the entire tract and is designed without a battery, instead relying on an externally applied magnetic field for inductive power supply . For the future, many enhancements have been proposed, including biopsy, real-time localization of the capsule, drug delivery, ultrasonic imaging, increasing motility by electrically inducing peristalsis, and utilizing an active locomotion system involving treads or legs . In a more dramatic approach to in vivo robotics, micro/nanotechnology is a multibillion dollar area of research [124, 125], including investigation for various medical robotic uses such as inexpensive directable drug delivery vehicles, radio-controlled biomolecules, tissue micromanipulation platforms, artificial mechanical white blood cells, and many other therapeutic approaches that may benefit from robots working at the cellular level [126–129]. Construction of functional systems is an ongoing area of research, particularly with respect to generating and powering motion. Many current prototypes are propelled and guided via magnetic fields, though some utilize external electrical energy sources [130, 131]. To the author’s knowledge, clinical trials have not begun for any medical micro/nanorobot. Medical robotics is a young and relatively unexplored field made possible by technical improvements over the past couple of decades. Currently available systems have been available for too short time to allow long-term studies. Nor are the benefits potentially provided by medical robots fully understood. Medical robots have only passed through a few technological generations and the technology continues to change and leap into new areas. Yet by looking at the current market and representative research systems, educated guesses can be made about the impacts of robots on near-future medicine. In surgical robotics, there has been a trend away from autonomous or even semiautonomous motions, and toward synergistic manipulation and virtual fixtures. Thus, the robot acts as a guidance tool, providing information (and possibly a physical nudge) to keep the surgeon on target. Such use requires accurate localization of the tissues in the surgical site, even as the tissues are manipulated during surgery. Improved imaging systems (e.g., Explorer, an intraoperative soft tissue tracker by Pathfinder Therapeutics ) or robot compatibility with MRI or CT will provide that localization. In particular, MRI-guided robots will benefit from intraoperative 3D images with excellent soft tissue contrast and accurate registration between the tool and the tissue, thus allowing precise virtual fixtures, “snap-to” and “stand-off” behaviors. Further, such imaging will allow modeling and rapid prototyping of patient-specific templates/jigs/implants. The physical designs for medical robots will continue to improve, reducing expense and size, while minimizing or compensating for nonidealities such as flexion, for example, the CRIGOS robot . With better physical designs, semiautonomous behavior will likely become more useful. “Macros” may become commonplace, wherein the surgeon presses a button and the robot performs a preprogrammed motion, such as passing a suture needle between graspers, or the Sensei’s autoretract feature . Robots will see more use for medical training purposes, bolstered by improved tissue-modeling capabilities, by the increasing objectivity in healthcare assessment, by advances in computer simulations, and as a result of increased data mining arising naturally from improved data connectivity between devices and between institutions. Some such systems are already available, such as the aforementioned da Vinci Skills Simulator, the Virtual I.V. Simulator by Laerdal, and the EndoscopyVR Surgical Simulator by CAE. For the same reasons, robotics will continue to make possible new medical procedures and treatments, such as new Single-Port Access procedures. Even as robots are developed for new medical areas, other tools may encroach on medical needs currently filled by robots. Medical robots must develop a firm basis in improved medical outcomes, or risk being displaced by pharmaceuticals, tissue engineering, gene therapy, and rapid innovation in manual tools (e.g., the SPIDER Surgical System by TransEnterix, and the EndoStitch by Covidien). To that end, improvements in medical robotics must address and solve real problems in healthcare, ultimately providing a clear improvement in quality of life when compared with the alternatives. - Intuitive Surgical Incorporation, “Webpage on da Vinci clinical evidence,” March 2012, http://www.intuitivesurgical.com/company/clinical-evidence. - Intuitive Surgical Incorporation, “Webpage on da Vinci regulatory approval,” March 2012, http://www.intuitivesurgical.com/company/regulatory-clearance.html. - H. Lavery, D. Samadi, and A. Levinson, “Not a zero-sum game: the adoption of robotics has increased overall prostatectomy utilization in the united states,” in Proceedings of the American Urological Association Annual Meeting, Poster Session, Washington, DC, USA, 2011. - R. D. Howe and Y. Matsuoka, “Robotics for surgery,” Annual Review of Biomedical Engineering, vol. 1, pp. 211–240, 1999. - B. Davies, “A review of robotics in surgery,” Proceedings of the Institution of Mechanical Engineers H, vol. 214, no. 1, pp. 129–140, 2000. - R. H. Taylor and D. Stoianovici, “Medical robotics in computer-integrated surgery,” IEEE Transactions on Robotics and Automation, vol. 19, no. 5, pp. 765–781, 2003. - A. R. Lanfranco, A. E. Castellanos, J. P. Desai, and W. C. Meyers, “Robotic surgery: a current perspective,” Annals of Surgery, vol. 239, no. 1, pp. 14–21, 2004. - P. Berkelman, J. Troccaz, and P. Cinquin, “Body-supported medical robots: a survey,” Journal of Robotics and Mechatronics, vol. 16, pp. 513–519, 2004. - L. Guo, X. Pan, Q. Li, F. Zheng, and Z. Bao, “A survey on the gastrointestinal capsule micro-robot based on wireless and optoelectronic technology,” Journal of Nanoelectronics and Optoelectronics, vol. 7, no. 2, pp. 123–127, 2012. - C. Stüer, F. Ringel, M. Stoffel, A. Reinke, M. Behr, and B. Meyer, “Robotic technology in spine surgery: current applications and future developments,” Intraoperative Imaging, vol. 109, pp. 241–245, 2011. - S. Badaan and D. Stoianovici, “Robotic systems: past, present, and future,” in Robotics in Genitourinary Surgery, pp. 655–665, Springer, New York, NY, USA, 2011. - I. Singh, “Robotics in urological surgery: review of current status and maneuverability, and comparison of robot-assisted and traditional laparoscopy,” Computer Aided Surgery, vol. 16, no. 1, pp. 38–45, 2011. - G. P. Moustris, S. C. Hiridis, K. M. Deliparaschos, and K. M. Konstantinidis, “Evolution of autonomous and semi-autonomous robotic surgical systems: a review of the literature,” International Journal of Medical Robotics and Computer Assisted Surgery, vol. 7, no. 4, pp. 375–392, 2011. - B. Challacombe and D. Stoianovici, “The basic science of robotic surgery,” in Urologic Robotic Surgery in Clinical Practice, pp. 1–23, 2009. - H. Kenngott, L. Fischer, F. Nickel, J. Rom, J. Rassweiler, and B. Muller-Stich, “Status of robotic assistance: a less traumatic and more accurate minimally invasive surgery?” Langenbeck's Archives of Surgery, vol. 397, no. 3, pp. 1–9, 2012. - P. Gomes, “Surgical robotics: reviewing the past, analysing the present, imagining the future,” Robotics and Computer-Integrated Manufacturing, vol. 27, no. 2, pp. 261–266, 2011. - A. M. Okamura, M. J. Matarić, and H. I. Christensen, “Medical and health-care robotics,” IEEE Robotics and Automation Magazine, vol. 17, no. 3, pp. 26–37, 2010. - S. Najarian, M. Fallahnezhad, and E. Afshari, “Advances in medical robotic systems with specific applications in surgery—a review,” Journal of Medical Engineering and Technology, vol. 35, no. 1, pp. 19–33, 2011. - J. Rosen, B. Hannaford, and R. Satava, Eds., Surgical Robotics: Systems Applications and Visions, Springer, New York, NY, USA, 2011. - N. Nathoo, M. C. Çavuşoǧlu, M. A. Vogelbaum, and G. H. Barnett, “In touch with robotics: neurosurgery for the future,” Neurosurgery, vol. 56, no. 3, pp. 421–431, 2005. - T. Haidegger, L. Kovacs, G. Fordos, Z. Benyo, and P. Kazanzides, “Future trends in robotic neurosurgery,” in Proceedings of the 14th Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC '08), pp. 229–233, Springer, June 2008. - Y. S. Kwoh, J. Hou, E. A. Jonckheere, and S. Hayati, “A robot with improved absolute positioning accuracy for CT guided stereotactic brain surgery,” IEEE Transactions on Biomedical Engineering, vol. 35, no. 2, pp. 153–160, 1988. - D. Glauser, H. Fankhauser, M. Epitaux, J. L. Hefti, and A. Jaccottet, “Neurosurgical robot Minerva: first results and current developments,” Journal of Image Guided Surgery, vol. 1, no. 5, pp. 266–272, 1995. - T. R. K. Varma and P. Eldridge, “Use of the NeuroMate stereotactic robot in a frameless mode for functional neurosurgery,” International Journal of Medical Robotics and Computer Assisted Surgery, vol. 2, no. 2, pp. 107–113, 2006. - Q. H. Li, L. Zamorano, A. Pandya, R. Perez, J. Gong, and F. Diaz, “The application accuracy of the NeuroMate robot—a quantitative comparison with frameless and frame-based surgical localization systems,” Computer Aided Surgery, vol. 7, no. 2, pp. 90–98, 2002. - P. Morgan, T. Carter, S. Davis et al., “The application accuracy of the pathfinder neurosurgical robot,” in International Congress Series, vol. 1256, pp. 561–567, Elsevier, Amsterdam, The Netherlands, 2003. - G. Deacon, A. Harwood, J. Holdback et al., “The pathfinder image-guided surgical robot,” Proceedings of the Institution of Mechanical Engineers H, vol. 224, no. 5, pp. 691–713, 2010. - J. Brodie and S. Eljamel, “Evaluation of a neurosurgical robotic system to make accurate burr holes,” International Journal of Medical Robotics and Computer Assisted Surgery, vol. 7, no. 1, pp. 101–106, 2011. - L. Joskowicz, R. Shamir, Z. Israel, Y. Shoshan, and M. Shoham, “Renaissance robotic system for keyhole cranial neurosurgery: in-vitro accuracy study,” in Proceedings of the Simposio Mexicano en Ciruga Asistida por Computadora y Procesamiento de Imgenes Mdicas (MexCAS '11), 2011. - D. P. Devito, L. Kaplan, R. Dietl et al., “Clinical acceptance and accuracy assessment of spinal implants guided with spineassist surgical robot: retrospective study,” Spine, vol. 35, no. 24, pp. 2109–2115, 2010. - M. Yang, J. Jung, J. Kim et al., “Current and future of spinal robot surgery,” Korean Journal of Spine, vol. 7, no. 2, pp. 61–65, 2010. - J. E. Lang, S. Mannava, A. J. Floyd et al., “Robotic systems in orthopaedic surgery,” Journal of Bone and Joint Surgery B, vol. 93, no. 10, pp. 1296–1299, 2011. - W. L. Bargar, A. Bauer, and M. Börner, “Primary and revision total hip replacement using the robodoc system,” Clinical Orthopaedics and Related Research, vol. 354, pp. 82–91, 1998. - A. P. Schulz, K. Seide, C. Queitsch et al., “Results of total hip replacement using the Robodoc surgical assistant system: clinical outcome and evaluation of complications for 97 procedures,” International Journal of Medical Robotics and Computer Assisted Surgery, vol. 3, no. 4, pp. 301–306, 2007. - P. Kazanzides, J. Zuhars, B. Mittelstadt, and R. H. Taylor, “Force sensing and control for a surgical robot,” in Proceedings of the IEEE International Conference on Robotics and Automation, pp. 612–617, May 1992. - A. D. Pearle, P. F. O'Loughlin, and D. O. Kendoff, “Robot-assisted unicompartmental knee arthroplasty,” Journal of Arthroplasty, vol. 25, no. 2, pp. 230–237, 2010. - A. D. Pearle, D. Kendoff, V. Stueber, V. Musahl, and J. A. Repicci, “Perioperative management of unicompartmental knee arthroplasty using the MAKO robotic arm system (MAKOplasty),” American Journal of Orthopedics, vol. 38, no. 2, pp. 16–19, 2009. - C. Plaskos, P. Cinquin, S. Lavallée, and A. J. Hodgson, “Praxiteles: a miniature bone-mounted robot for minimal access total knee arthroplasty,” The International Journal of Medical Robotics and Computer Assisted Surgery, vol. 1, no. 4, pp. 67–79, 2005. - D. Koulalis, P. F. O'Loughlin, C. Plaskos, D. Kendoff, M. B. Cross, and A. D. Pearle, “Sequential versus automated cutting guides in computer-assisted total knee arthroplasty,” Knee, vol. 18, no. 6, pp. 436–442, 2010. - G. Brisson, T. Kanade, A. DiGioia, and B. Jaramaz, “Precision freehand sculpting of bone,” in Proceedings of the 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI '04), pp. 105–112, September 2004. - G. Brisson, The Precision Freehand Sculptor: a Robotic Tool for Less Invasive Joint Replacement Surgery, ProQuest, 2008. - P. L. Yen and B. L. Davies, “Active constraint control for image-guided robotic surgery,” Proceedings of the Institution of Mechanical Engineers H, vol. 224, no. 5, pp. 623–631, 2010. - A. G. Harrell and B. T. Heniford, “Minimally invasive abdominal surgery: lux et veritas past, present, and future,” American Journal of Surgery, vol. 190, no. 2, pp. 239–243, 2005. - G. Dogangil, B. L. Davies, and F. Rodriguez Y Baena, “A review of medical robotics for minimally invasive soft tissue surgery,” Proceedings of the Institution of Mechanical Engineers H, vol. 224, no. 5, pp. 653–679, 2010. - C. Kuo and J. Dai, “Robotics for minimally invasive surgery: a historical review from the perspective of kinematics,” in Proceedings of the International Symposium on History of Machines and Mechanisms, pp. 337–354, Springer, 2009. - S. J. Harris, F. Arambula-Cosio, and Q. Mei, “The probot—an active robot for prostate resection,” Proceedings of the Institution of Mechanical Engineers H, vol. 211, no. 4, pp. 317–325, 1997. - G. H. Ballantyne, “Robotic surgery, telerobotic surgery, telepresence, and telementoring: review of early clinical results,” Surgical Endoscopy and Other Interventional Techniques, vol. 16, no. 10, pp. 1389–1402, 2002. - G. T. Sung and I. S. Gill, “Robotic laparoscopic surgery: a comparison of the da Vinci and Zeus systems,” Urology, vol. 58, no. 6, pp. 893–898, 2001. - J. Marescaux, J. Leroy, M. Gagner et al., “Transatlantic robot-assisted telesurgery,” Nature, vol. 413, no. 6854, pp. 379–380, 2001. - P. Mozer, J. Troccaz, and D. Stoinaovici, “Robotics in urology: past, present, and future,” in Atlas of Robotic Urologic Surgery, L. Su, Ed., Current Clinical Urology, ch. 1, pp. 3–13, Springer, New York, NY, USA, 2011. - K. Shah and R. Abaza, “Comparison of intraoperative outcomes using the new and old generation da Vinci robot for robot-assisted laparoscopic prostatectomy,” British Journal of Urology International, vol. 108, no. 10, pp. 1642–1645, 2011. - J. Bodner, H. Wykypiel, G. Wetscher, and T. Schmid, “First experiences with the da Vinci operating robot in thoracic surgery,” European Journal of Cardio-Thoracic Surgery, vol. 25, no. 5, pp. 844–851, 2004. - A. Tewari, A. Srivasatava, and M. Menon, “A prospective comparison of radical retropubic and robot-assisted prostatectomy: experience in one institution,” British Journal of Urology International, vol. 92, no. 3, pp. 205–210, 2003. - S. Maeso, M. Reza, J. A. Mayol et al., “Efficacy of the da Vinci surgical system in abdominal surgery compared with that of laparoscopy: a systematic review and meta-analysis,” Annals of Surgery, vol. 252, no. 2, pp. 254–262, 2010. - R. E. Link, S. B. Bhayani, and L. R. Kavoussi, “A prospective comparison of robotic and laparoscopic pyeloplasty,” Annals of Surgery, vol. 243, no. 4, pp. 486–491, 2006. - A. Amodeo, A. Linares Quevedo, J. V. Joseph, E. Belgrano, and H. R. H. Patel, “Robotic laparoscopic surgery: cost and training,” Minerva Urologica e Nefrologica, vol. 61, no. 2, pp. 121–128, 2009. - W. Jeong, F. Petros, and C. Rogers, Robotic Surgery: Basic Instrumentation and Troubleshooting, ch. 72, Wiley-Blackwell, Hoboken, NJ, USA, 2012. - M. A. Lerner, M. Ayalew, W. J. Peine, and C. P. Sundaram, “Does training on a virtual reality robotic simulator improve performance on the da Vinci surgical system?” Journal of Endourology, vol. 24, no. 3, pp. 467–472, 2010. - K. Cleary and T. M. Peters, “Image-guided interventions: technology review and clinical applications,” Annual Review of Biomedical Engineering, vol. 12, pp. 119–142, 2010. - M. E. Hagen, O. J. Wagner, I. Inan et al., “Robotic single-incision transabdominal and transvaginal surgery: initial experience with intersecting robotic arms,” International Journal of Medical Robotics and Computer Assisted Surgery, vol. 6, no. 3, pp. 251–255, 2010. - M. Kroh, K. El-Hayek, S. Rosenblatt et al., “First human surgery with a novel single-port robotic system: cholecystectomy using the da Vinci Single-Site platform,” Surgical Endoscopy, vol. 25, no. 11, pp. 3566–3573, 2011. - M. Stark, T. Benhidjeb, S. Gidaro, and E. Morales, “The future of telesurgery: a universal system with haptic sensation,” Journal of the Turkish-German Gynecological Association, vol. 13, no. 1, pp. 74–76, 2012. - S. DiMaio and S. Salcudean, “Needle steering and model-based trajectory planning,” in Proceedings of the 6th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI '03), pp. 33–40, 2003. - H. Delingette, “Toward realistic soft-tissue modeling in medical simulation,” Proceedings of the IEEE, vol. 86, no. 3, pp. 512–523, 1998. - A. Melzer, B. Gutmann, T. Remmele et al., “Innomotion for percutaneous image-guided interventions,” IEEE Engineering in Medicine and Biology Magazine, vol. 27, no. 3, pp. 66–73, 2008. - M. Li, A. Kapoor, D. Mazilu, and K. A. Horvath, “Pneumatic actuated robotic assistant system for aortic valve replacement under MRI guidance,” IEEE Transactions on Biomedical Engineering, vol. 58, no. 2, pp. 443–451, 2011. - S. Zangos, A. Melzer, K. Eichler et al., “MR-compatible assistance system for biopsy in a high-field-strength system: initial results in patients with suspicious prostate lesions,” Radiology, vol. 259, no. 3, pp. 903–910, 2011. - H. J. Swan, W. Ganz, J. Forrester, H. Marcus, G. Diamond, and D. Chonette, “Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter,” The New England Journal of Medicine, vol. 283, no. 9, pp. 447–451, 1970. - M. R. Franz, D. Burkhoff, and H. Spurgeon, “In vitro validation of a new cardiac catheter technique for recording monophasic action potentials,” European Heart Journal, vol. 7, no. 1, pp. 34–41, 1986. - J. M. Gore, R. J. Goldberg, D. H. Spodick, J. S. Alpert, and J. E. Dalen, “A community-wide assessment of the use of pulmonary artery catheters in patients with acute myocardial infarction,” Chest, vol. 92, no. 4, pp. 721–727, 1987. - D. Steven, H. Servatius, T. Rostock et al., “Reduced fluoroscopy during atrial fibrillation ablation: benefits of robotic guided navigation,” Journal of Cardiovascular Electrophysiology, vol. 21, no. 1, pp. 6–12, 2010. - V. Y. Reddy, P. Neuzil, Z. J. Malchano et al., “View-synchronized robotic image-guided therapy for atrial fibrillation ablation: experimental validation and clinical feasibility,” Circulation, vol. 115, no. 21, pp. 2705–2714, 2007. - K. R. J. Chun, B. Schmidt, B. Köktürk et al., “Catheter ablation—new developments in robotics,” Herz, vol. 33, no. 8, pp. 586–589, 2008. - C. V. Riga, C. D. Bicknell, D. Wallace, M. Hamady, and N. Cheshire, “Robot-assisted antegrade in-situ fenestrated stent grafting,” CardioVascular and Interventional Radiology, vol. 32, no. 3, pp. 522–524, 2009. - S. Ernst, F. Ouyang, C. Linder et al., “Initial experience with remote catheter ablation using a novel magnetic navigation system,” Circulation, vol. 109, no. 12, pp. 1472–1475, 2004. - J. K. R. Chun, S. Ernst, S. Matthews et al., “Remote-controlled catheter ablation of accessory pathways: results from the magnetic laboratory,” European Heart Journal, vol. 28, no. 2, pp. 190–195, 2007. - L. Leksell, “Stereotactic radiosurgery,” Journal of Neurology Neurosurgery and Psychiatry, vol. 46, no. 9, pp. 797–803, 1983. - R. Schulz and N. Agazaryan, Shaped-Beam Radiosurgery: State of the Art, Springer, New York, NY, USA, 2011. - J. R. Adler Jr., S. D. Chang, M. J. Murphy, J. Doty, P. Geis, and S. L. Hancock, “The cyberknife: a frameless robotic system for radiosurgery,” Stereotactic and Functional Neurosurgery, vol. 69, no. 1–4, pp. 124–128, 1997. - G. J. Gagnon, N. M. Nasr, J. J. Liao et al., “Treatment of spinal tumors using cyberKnife fractionated stereotactic radiosurgery: pain and quality-of-life assessment after treatment in 200 patients,” Neurosurgery, vol. 64, no. 2, pp. 297–306, 2009. - M. Hoogeman, J. B. Prevost, J. Nuyttens, J. Poll, P. Levendag, and B. Heijmen, “Clinical accuracy of the respiratory tumor tracking system of the cyberknife: assessment by analysis of log files,” International Journal of Radiation Oncology *Biology* Physics, vol. 74, no. 1, pp. 297–303, 2009. - J. P. Rock, S. Ryu, F. F. Yin, F. Schreiber, and M. Abdulhak, “The evolving role of stereotactic radiosurgery and stereotactic radiation therapy for patients with spine tumors,” Journal of Neuro-Oncology, vol. 69, no. 1–3, pp. 319–334, 2004. - R. E. Wurm, S. Erbel, I. Schwenkert et al., “Novalis frameless image-guided noninvasive radiosurgery: initial experience,” Neurosurgery, vol. 62, no. 5, pp. A11–A17, 2008. - Z. Chang, T. Liu, J. Cai, Q. Chen, Z. Wang, and F. Yin, “Evaluation of integrated respiratory gating systems on a novalis tx system,” Journal of Applied Clinical Medical Physics, vol. 12, no. 3, article 3495, 2011. - A. Liu, N. Agazaryan, C. Yu, H. Han, T. Schultheiss, and J. Wong, “A multi-center consortium study of competing platforms for intracranial stereotactic irradiation,” International Journal of Radiation Oncology *Biology* Physics, vol. 72, supplement 1, pp. S213–S213, 2008. - M. Abacioglu, “Advances in technology in radiation oncology,” Oncology, vol. 2, no. 1, pp. 11–14, 2012. - H. R. Halperin, N. Paradis, J. P. Ornato et al., “Cardiopulmonary resuscitation with a novel chest compression device in a porcine model of cardiac arrest: improved hemodynamics and mechanisms,” Journal of the American College of Cardiology, vol. 44, no. 11, pp. 2214–2220, 2004. - A. Hallstrom, T. D. Rea, M. R. Sayre et al., “Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial,” Journal of the American Medical Association, vol. 295, no. 22, pp. 2620–2628, 2006. - R. Palmer, “Integrated diagnostic and treatment devices for enroute critical care of patients within theater,” in Proceedings of the RTO Human Factors and Medicine Panel Symposium, Amsterdam, The Netherlands, October 2010. - R. Seymour, B. Engbretson, K. Kott et al., “Comparison between the C-leg microprocessor-controlled prosthetic knee and non-microprocessor control prosthetic knees: a preliminary study of energy expenditure, obstacle course performance, and quality of life survey,” Prosthetics and Orthotics International, vol. 31, no. 1, pp. 51–61, 2007. - O. Otr, H. A. Reinders-Messelink, R. M. Bongers, H. Bouwsema, and C. K. Van Der Sluis, “The i-LIMB hand and the DMC plus hand compared: a case report,” Prosthetics and Orthotics International, vol. 34, no. 2, pp. 216–220, 2010. - K. Low, “Robot-assisted gait rehabilitation: from exoskeletons to gait systems,” in Proceedings of the Defense Science Research Conference and Expo (DSR '11), pp. 1–10, August 2011. - J. Rosen and J. C. Perry, “Upper limb powered exoskeleton,” International Journal of Humanoid Robotics, vol. 4, no. 3, pp. 529–548, 2007. - H. Kazerooni, “Exoskeletons for human performance augmentation,” in Springer Handbook of Robotics, B. Siciliano and O. Khatib, Eds., Springer, New York, NY, USA, 2008. - R. Bogue, “Exoskeletons and robotic prosthetics: a review of recent developments,” Industrial Robot, vol. 36, no. 5, pp. 421–427, 2009. - M. J. Topping and J. K. Smith, “The development of Handy 1. A robotic system to assist the severely disabled,” Technology and Disability, vol. 10, no. 2, pp. 95–105, 1999. - M. Hillman, “Rehabilitation robotics from past to present—a historical perspective,” in Advances in Rehabilitation Robotics, pp. 25–44, Springer, New York, NY, USA, 2004. - A. Waldner, C. Werner, and S. Hesse, “Robot assisted therapy in neurorehabilitation,” Europa Medicophysica, vol. 44, supplement 1, pp. 1–3, 2008. - J. L. Dallaway, R. D. Jackson, and P. H. A. Timmers, “Rehabilitation robotics in Europe,” IEEE Transactions on Rehabilitation Engineering, vol. 3, no. 1, pp. 35–45, 1995. - M. Busnel, R. Cammoun, F. Coulon-Lauture, J. M. Détriché, G. Le Claire, and B. Lesigne, “The robotized workstation “MASTER” for users with tetraplegia: description and evaluation,” Journal of Rehabilitation Research and Development, vol. 36, no. 3, pp. 217–229, 1999. - M. Ceccarelli, “Problems and issues for service robots in new applications,” International Journal of Social Robotics, vol. 3, no. 3, pp. 299–312, 2011. - M. J. H. Lum, D. C. W. Friedman, G. Sankaranarayanan et al., “The RAVEN: design and validation of a telesurgery system,” International Journal of Robotics Research, vol. 28, no. 9, pp. 1183–1197, 2009. - A. Simorov, R. Otte, C. Kopietz, and D. Oleynikov, “Review of surgical robotics user interface: what is the best way to control robotic surgery?” Surgical Endoscopy, vol. 26, no. 8, pp. 2117–2125, 2012. - C. Kuo, J. Dai, and P. Dasgupta, “Kinematic design considerations for minimally invasive surgical robots: an overview,” The International Journal of Medical Robotics and Computer Assisted Surgery, vol. 8, no. 2, pp. 127–145, 2012. - C. Wagner, N. Stylopoulos, and R. Howe, “The role of force feedback in surgery: analysis of blunt dissection,” in Proceedings of the 10th Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems, vol. 2002, Citeseer, 2002. - M. Tavakoli, R. V. Patel, and M. Moallem, “Haptic interaction in robot-assisted endoscopic surgery: a sensorized end-effector,” The International Journal of Medical Robotics and Computer Assisted Surgery, vol. 1, no. 2, pp. 53–63, 2005. - A. M. Okamura, “Haptic feedback in robot-assisted minimally invasive surgery,” Current Opinion in Urology, vol. 19, no. 1, pp. 102–107, 2009. - U. Hagn, R. Konietschke, A. Tobergte et al., “DLR MiroSurge: a versatile system for research in endoscopic telesurgery,” International Journal of Computer Assisted Radiology and Surgery, vol. 5, no. 2, pp. 183–193, 2010. - S. Thielmann, U. Seibold, R. Haslinger et al., “MICA—a new generation of versatile instruments in robotic surgery,” in Proceedings of the 23rd IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS '10), pp. 871–878, October 2010. - R. Konietschke, T. Ortmaier, H. Weiss, G. Hirzinger, and R. Engelke, “Manipulability and accuracy measures for a medical robot in minimally invasive surgery,” in Advances in Robot Kinematics, 2004. - G. Sutherland, P. McBeth, and D. Louw, “Neuroarm: an mr compatible robot for microsurgery,” in International Congress Series, vol. 1256, pp. 504–508, Elsevier, Amsterdam, The Netherland, 2003. - M. J. Lang, A. D. Greer, and G. R. Sutherland, “Intra-operative robotics: NeuroArm,” Intraoperative Imaging, vol. 109, pp. 231–236, 2011. - D. Stoianovici, D. Song, D. Petrisor et al., “‘MRI Stealth’ robot for prostate interventions,” Minimally Invasive Therapy and Allied Technologies, vol. 16, no. 4, pp. 241–248, 2007. - P. Garcia, J. Rosen, C. Kapoor et al., “Trauma pod: a semi-automated telerobotic surgical system,” International Journal of Medical Robotics and Computer Assisted Surgery, vol. 5, no. 2, pp. 136–146, 2009. - S. G. Yuen, P. M. Novotny, and R. D. Howe, “Quasiperiodic predictive filtering for robot-assisted beating heart surgery,” in Proceedings of the IEEE International Conference on Robotics and Automation (ICRA '08), pp. 3875–3880, May 2008. - N. Patronik, C. Riviere, S. El Qarra, and M. Zenati, “The heartlander: a novel epicardial crawling robot for myocardial injections,” in International Congress Series, vol. 1281, pp. 735–739, Elsevier, Amsterdam, The Netherland, 2005. - D. Moral Del Agua, N. A. Wood, and C. N. Riviere, “Improved synchronization of heartlander locomotion with physiological cycles,” in Proceedings of the 37th Annual Northeast Bioengineering Conference (NEBEC '11), April 2011. - T. Wortman, A. Meyer, O. Dolghi et al., “Miniature surgical robot for laparoendoscopic single-incision colectomy,” Surgical Endoscopy, vol. 26, pp. 727–731, 2012. - Y. Hayashi, H. Yamamoto, T. Yano, and K. Sugano, “Review: diagnosis and management of mid-gastrointestinal bleeding by double-balloon endoscopy,” Therapeutic Advances in Gastroenterology, vol. 2, no. 2, pp. 109–117, 2009. - A. Van Gossum, M. M. Navas, I. Fernandez-Urien et al., “Capsule endoscopy versus colonoscopy for the detection of polyps and cancer,” The New England Journal of Medicine, vol. 361, no. 3, pp. 264–270, 2009. - D. Cassilly, S. Kantor, L. C. Knight et al., “Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy,” Neurogastroenterology and Motility, vol. 20, no. 4, pp. 311–319, 2008. - C. Mc Caffrey, O. Chevalerias, C. O'Mathuna, and K. Twomey, “Swallowable-capsule technology,” IEEE Pervasive Computing, vol. 7, no. 1, pp. 23–29, 2008. - A. Moglia, A. Menciassi, and P. Dario, “Recent patents on wireless capsule endoscopy,” Recent Patents on Biomedical Engineering, vol. 1, no. 1, pp. 24–33, 2008. - M. C. Roco, “Nanotechnology: convergence with modern biology and medicine,” Current Opinion in Biotechnology, vol. 14, no. 3, pp. 337–346, 2003. - M. Copot, A. Popescu, I. Lung, and A. Moldovanu, “Achievements and perspectives in the field of nanorobotics,” The Romanian Review Precision Mechanics, Optics and Mechatronics, vol. 19, no. 36, pp. 61–66, 2009. - R. A. Freitas, “What is nanomedicine?” Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 1, no. 1, pp. 2–9, 2005. - L. Zhang, J. J. Abbott, L. Dong, B. E. Kratochvil, D. Bell, and B. J. Nelson, “Artificial bacterial flagella: fabrication and magnetic control,” Applied Physics Letters, vol. 94, no. 6, Article ID 064107, 2009. - G. Kósa, M. Shoham, and M. Zaaroor, “Propulsion of a swimming micro medical robot,” in Proceedings of the IEEE International Conference on Robotics and Automation (ICRA '05), pp. 1327–1331, April 2005. - G. Dogangil, O. Ergeneman, J. J. Abbott et al., “Toward targeted retinal drug delivery with wireless magnetic microrobots,” in Proceedings of the IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS '08), pp. 1921–1926, September 2008. - H. Li, J. Tan, and M. Zhang, “Dynamics modeling and analysis of a swimming microrobot for controlled drug delivery,” IEEE Transactions on Automation Science and Engineering, vol. 6, no. 2, pp. 220–227, 2009. - T. Ebefors, J. Mattsson, E. Kalvesten, and G. Stemme, “A walking silicon micro-robot,” in Proceedings of the 10th International Conference on Solid-State Sensors and Actuators (Transducers '99), pp. 1202–1205, 1999. - P. Dumpuri, L. W. Clements, B. M. Dawant, and M. I. Miga, “Model-updated image-guided liver surgery: preliminary results using surface characterization,” Progress in Biophysics and Molecular Biology, vol. 103, no. 2-3, pp. 197–207, 2010. - G. Brandt, A. Zimolong, L. Carrât et al., “CRIGOS: a compact robot for image-guided orthopedic surgery,” IEEE Transactions on Information Technology in Biomedicine, vol. 3, no. 4, pp. 252–260, 1999.

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CHRONIC WASTING DISEASE Boone and Crockett Club Helps Form Alliance The Boone and Crockett Club, Rocky Mountain Elk Foundation and Mule Deer Foundation formed a partnership alliance to address chronic wasting disease (CWD). The organizations agreed to pool resources and collaborate on ways to positively address the One of the greatest needs is the dissemination of timely and accurate information regarding CWD to the organizations members, the general public and the media. Some activities include: - Consideration of grant requests for specific CWD research and management projects - Working with state and federal agencies to develop policy recommendations for the management and eradication of CWD - Providing expert testimony to select decision makers such as state wildlife commissions, state legislatures, and the United For most current up-to-date information visit the Alliance's web site at www.cwd-info.org Free CWD Video Is Here and Now The Chronic Wasting Disease Alliance (CWDA) and American Outdoor Productions (AOP) have partnered to provide a free, on-line chronic wasting disease (CWD) education video, reports the Wildlife Management Institute. Titled "Shedding Light on CWD," the video presents current and comprehensive status information on CWD and shows proper field-processing techniques for deer, elk and moose harvested in CWD-positive areas. Nearly 35 minutes in length and offered at two connection speeds, the video contains 19 chapters such as "CWD Facts," "State Regulations," "Field Dressing Precautions" and "CWD Testing." Each chapter can be viewed independently to allow users to access targeted information that pertains to their specific question or concern. Combining the production expertise of AOP and technical input from CWDA, "Shedding Light on CWD" was initiated in 2004. Originally available only through sales, the video became free for on-line viewing after CWDA purchased the rights to the production from AOP last year. Since then, the video has undergone extensive updating to make it current with the most recent CWD information, regulations and research available. AOP currently is providing on-line hosting services for the video and will cooperate with CWDA to provide informational updates. "American Outdoor Productions was proud to be a partner in this important project," said AOP’s Director of Business Bob Fiesthumel, "The synergy involved in developing this video was inspiring. We at AOP are happy to continue to play a role in ensuring that hunters throughout the CWD-affected states and provinces are provided only the best, up-to-date intelligence on this disease." To view the video, visit http://www.cwd-info.org and click on the Watch Shedding Light on CWD link, or visit http://www.welcometohunting.com/video/CWD/cable/cwd.html to view or link to the video directly.

Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease © Chavez-Tapia et al; licensee BioMed Central Ltd. 2012 Received: 14 September 2011 Accepted: 1 March 2012 Published: 1 March 2012 In vitro exposure of liver cells to high concentrations of free fatty acids (FFA) results in fat overload which promotes inflammatory and fibrogenic response similar to those observed in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Since the mechanisms of this event have not been fully characterized, we aimed to analyze the fibrogenic stimuli in a new in vitro model of NASH. HuH7 cells were cultured for 24 h in an enriched medium containing bovine serum albumin and increasing concentrations of palmitic and oleic acid at a molar ratio of 1:2 (palmitic and oleic acid, respectively). Cytotoxic effect, apoptosis, oxidative stress, and production of inflammatory and fibrogenic cytokines were measured. FFA induces a significant increment in the intracellular content of lipid droplets. The gene expression of interleukin-6, interleukin-8 and tumor necrosis factor alpha was significantly increased. The protein level of interleukin-8 was also increased. Intracellular lipid accumulation was associated to a significant up-regulation in the gene expression of transforming growth factor beta 1, alpha 2 macroglobulin, vascular endothelial growth factor A, connective tissue growth factor, insulin-like growth factor 2, thrombospondin 1. Flow cytometry analysis demonstrated a significant increment of early apoptosis and production of reactive oxygen species. The exposure of hepatocytes to fatty acids elicits inflammation, increase of oxidative stress, apoptosis and production of fibrogenic cytokines. These data support a primary role of FFA in the pathogenesis of NAFLD and NASH. Non-alcoholic fatty liver disease (NAFLD) is a common disease associated to obesity and increased visceral fat. This condition has the potential to develop hepatic fibrosis and end-stage liver disease, and is associated with several non-hepatic related complications . Liver fibrosis is a complex event that could be conceptually divided in three phases: initiation, perpetuation and resolution: each of these phases has specific pathways. Classically, the hepatic stellate cell and immune cells are the main players in the fibrotic process but the role of the hepatocyte is also important, mainly in the initiation phase due to production of several fibrogenic stimuli, particularly reactive oxygen species (ROS) and apoptosis . Recently it has been described the production by the hepatocyte of several cytokines involved in the fibrogenesis, and in vitro studies with liver cells exposed to toxic amounts of free fatty acids (FFA) demonstrated that this condition could promote and inflammatory and fibrogenic response . The hepatocyte-mediated fibrogenic response is regulated by cytokines involved in proliferation (as the transforming growth factor beta 1 [TGFβ1], alpha 2 macroglobulin [Α2M], vascular endothelial growth factor A [VEGFA], connective tissue growth factor [CTGF], and insulin-like growth factor 2 [IGF2]) and in the regulation of apoptosis (as the nerve growth factor [NGF], and thrombospondin 1 [THBS1]) . In spite of its importance, the fibrogenic response has not been fully explored in NAFLD, and it is also unknown if non toxic amounts of fatty acids are able to induce an inflammatory and fibrogenic response in the hepatocytes. The aim of this study was therefore to analyze the production of fibrogenic stimulus in a new in vitro model of non-alcoholic steatohepatitis (NASH). Cell culture medium Dulbecco's modified Eagle's high glucose medium (DMEM) (ECB7501L), L- Glutamine (ECB3000D), Penicillin/Streptomycin (ECB3001D), were obtained from Euro-clone (Milan, Italy). Bicinconinc acid solution-kit (B9643); bovine albumin Cohn V fraction (A4503); dimethyl sulphoxide (DMSO) (D2438); fetal bovine serum (F7524); Hoechst 33258 (B1155); hydrogen peroxide (H1009); 3-(4,5 dimethylthiazol-yl-)-2,5-dipheniltetrazoliumbromide (MTT) (M2128); N-acetyl-L-cysteine (NAC) (A9165); Nile Red (N3013); oleic acid (C18:1) (O1008); palmitic acid (C16:0) (P0500); paraformaldehyde (P6148), phosphate-buffered saline (PBS) (D5652); propidium iodide (PI)(P4170) and Tri-Reagent (T9424) were from Sigma Chemical (St.Louis, MO, USA). iScript™ cDNA Synthesis kit (170-8890) and iQ SYBR Green Supermix (170-8860) were purchased from Bio-Rad Laboratories (Hercules, CA, USA). 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) (D399) was obtained from Molecular Probes (Milan, Italy). Human annexin V-FITC Kit (BMS306FICE); Instant ELISA kit interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha (BMS213INSTCE; BMS204/3INSTCE; BMS223INSTCE respectively) were purchased to Bender MedSystems GmbH (Vienna, Austria) Cell culture and FFA treatment Hepatoma derived cell line HuH7 (JHSRRB, Cat #JCRB0403) were obtained from the Health Science Research Resources Bank (Osaka, Japan). Cells were grown in DMEM high glucose medium supplemented with 10% v/v fetal bovine serum, 2 mM L-Glutamine, 10,000 U/mL penicillin and 10 mg/mL streptomycine at 37°C under 5% CO2, in a 95% humidified atmosphere. For the treatment, palmitic and oleic acid 0.1 M stock solutions were prepare by dissolving FFA in DMSO. The cells were exposed for 24 h to increasing concentrations of a fresh mixture of exogenous FFA (100; 200; 400; 600 and 1200 μM) in molar ratio 1:2 palmitic:oleic respectively. Since albumin concentration is an important factor in determining the concentration of available FFA, the FFA were complexed with bovine serum albumin at a 4:1 molar ratio taking into consideration the albumin concentration already present in the medium due to the FBS supplementation. The experimental doses were determined in advance by performing dose curves and by assessing cell viability which was always higher than 85% as compared to control cells (100% viability) treated with the equivalent concentration v/v of the vehicle (DMSO). Cell viability was assessed using the MTT colorimetric assay. When taken up by living cells, MTT is converted from a yellow to a water insoluble blue-colored precipitate by cellular dehydrogenases . Briefly, 4 × 104 cells/cm2 were plated in 24 well dish and allowed to adhere overnight. The following day the cells were treated as described above. After 24 h of treatment, the medium was removed and the treatment was followed by addition of 0.5 mg/mL of MTT and incubation at 37°C for 1 h. The medium was then removed, the cells were lysed and the resulting blue formazan crystals were solved in DMSO. The absorbance of each well was read on a microplate reader (Beckman Coulter LD 400 C Luminescence detector) at 570 nm. The absorbance of the untreated controls was taken as 100% survival. Data are expressed as mean ± SD of three independent experiments. Fluorimetric determination of intracellular fat content - Nile red staining Intracellular fat content was determined fluorimetrically based on Nile Red staining, a vital lipophilic dye used to label fat accumulation in the cytosol [7, 8]. After 24 h of FFA exposure, adherent monolayer cells were washed twice with PBS and detached by tripsinization. After a 5 min centrifugation at 1500 rpm, the cell pellet was resuspended in 3 mL of PBS and incubated with 0.75 μg/mL Nile red dye for 15 min at room temperature. Nile red intracellular fluorescence was determined by flow cytofluorometry using a Becton Dickinson FACSCalibur System on the FL2 emission channel through a 585 ± 21 nm band pass filter, following excitation with an argon ion laser source at 488 nm . Data were collected in 10,000 cells and analyzed using Cellquest software from BD Biosciences (San Jose, CA, USA). Intracellular lipid droplets analysis by fluorescence microscopy HuH7 cells were seeded in a coverslip and exposed to FFA for 24 h as previously described. Cells were then washed with PBS twice, and fixed with 3% paraformaldehide for 15 min. Intracellular neutral lipids were stained with Nile Red (3.3 μg/mL) for 15 min. Cell nuclei were stained with Hoescht 33258 dye for 15 min. All the staining procedure was carried out at room temperature by protecting the samples from the direct light. Images were acquired with an inverted fluorescence microscope (Leica DM2000, Wetzlar Germany) Extraction of RNA and cDNA synthesis After the treatment, the medium was removed, cells were washed twice with PBS and after centrifugation, total RNA isolated using Tri-Reagent kit according to manufacturer's instructions. Briefly, cells were lysed with the reagent, chloroform was added and cellular RNA was precipitated by isopropyl alcohol. After washing with 75% ethanol, the RNA pellet was dissolved in nuclease-free water and stored at -80°C until further analysis. RNA was quantified spectrophotometrically at 260 nm in a Beckman Coulter DU®730 spectrophotometer (Fullertone, CA, USA). The RNA purity was evaluated by measuring the ratio A260/A280, considering RNA with appropriate purity those showing values between 1.8 and 2.0; its integrity was evaluated by gel electrophoresis. The integrity of RNA was assessed on standard 1% agarose/formaldehyde gel. Isolated RNA was resuspended in RNAse free water and stored at -80°C until analysis. Total RNA (1 μg) was reverse transcribed using iScript™ cDNA Synthesis kit BioRad according to manufacturer's instructions. Retrotranscription was performed in a Thermal Cycler (Gene Amp PCR System 2400, Perkin Elmer, Boston, MA, USA) in agreement with the reaction protocol proposed by the manufacturer's: 5 min at 25°C (annealing), 45 min at 42°C (cDNA synthesis), and 5 min at 85°C (enzyme denaturation). Real time quantitative PCR Set of primers used in Real-time quantitative PCR Tumor necrosis factor alpha Transforming growth factor beta Alpha 2 macroglobulin Vascular endothelial growth factor A Nerve growth factor Connective tissue growth factor Insulin-like growth factor 2 IL-6, IL-8 and TNF-alpha release The cytokine released in the culture media was determined by Instant ELISA (Bender MedSystems GmbH; Vienna Austria) according to manufacturer's instructions. Cells were cultured and treated as previously described. The culture media was collected after 24 h, possible contamination of cellular fractions was eliminated by centrifugation and the test performed in cell-free supernatant. According to the manufacturer the lowest detection limits were: 0.92 pg/mL for IL-6, 1.3 pg/mL for IL-8 and 1.65 pg/mL for TNF-alpha. Intracellular ROS generation by H2DCFDA Intracellular ROS generation was measured by the use of the cell permeable fluorogenic substrate H2DCFDA. This non fluorescent probe is easily taken up by cells and, after intracellular cleavage of the acetyl groups, is trapped and may be oxidized to the fluorescent compound 2',7'-dichlorofluorescin (DCF; the monitored fluorophore) by intracellular ROS . Cells were exposed to FFA for 24 h and after the treatment, adherent cells were washed with PBS, and loaded with 10 μM H2DCFDA for 15 min at 37°C. The fluorescence was measured by using a Spectrofluorometer Jasco FP-770 (Excitation wavelength 505 nm and Emission 525 nm). Fluorescence was normalized by the μg of protein assessed by bicinconinic acid protein assay and expressed as AU/μg of protein. The intracellular ROS production was also assessed by flow cytometric analysis by using Becton Dickinson FACSCalibur System. Briefly, attached cells were harvested by tripsinization, washed in PBS by centrifugation, and incubated with 5 μM H2DCFDA for 30 min at 37°C in PBS, to exclude hydrogen peroxide generation in phenol red containing media. The cells were washed in PBS and the pellet was suspended in 500 μL of PBS. PI staining was performed to assess non viable cells. Cells within a negative control gate for PI fluorescence were back-gated (FL2) and the fluorescence histogram for H2DCFDA (FL1) was applied for the living cells . Considering the potential anti-oxidant effect of albumin , the albumin concentration was kept the same in the controls and in the treated samples. Cells exposed to 400 μM hydrogen peroxide were considered as positive control. In order establish if the ROS production induced by FFA could be reversed by an antioxidant agent, cells were co-treated with FFA and 300 μM n-acetylcysteine (NAC). The optimal NAC concentration was established by performing dose curve analysis by MTT, at the used concentration cell viability was unaltered (data not shown). Data were collected for 10,000 cells and analyzed using CellQuest software from BD Biosciences (San Jose, CA). Assessment of apoptosis During apoptosis, phosphatidyl serine is exposed from the inner to the outer portion of the membrane and becomes available to bind to the Annexin-V/FITC conjugate. Accordingly, only cells prone to apoptosis will stain positive for Annexin-V/FITC . The cells were harvested by gentle tripsinization which was inactivated by adding medium with 10% FBS. Cells were washed, the pellet suspended in the incubation buffer (10 mM Hepes/NAOH, pH 7.40, 140 mM NaCl, 5 mM CaCl2) adjusting cell density to 5 × 106 cell/mL, and 1 × 106 cells were incubated with 5 μL Annexin V-FITC and 5 μL PI for 10 min at room temperature. The cells were diluted with the incubation buffer to a final volume of 600 μL and analyzed by flow cytometer using 488 nm excitation and 515 nm band-pass filter for fluorescein detection (FL1) and a filter > 600 nm for PI detection (FL2). Data were collected for 10,000 cells and analyzed using CellQuest software from BD Biosciences (San Jose, CA). Unless otherwise indicated all the data are expressed as mean ± standard deviation of three independent experiments (biological replicates). Differences between groups were compared by using Student's t test. The level of significance was set at a P-value of 0.05. Toxicity of the model The addition of increasing concentrations of FFA (palmitic/oleic 1:2 molar ratio) did not affect the cell viability measured by MTT Test (data not shown). To assess the effect of the vehicle in which FFA were solubilized, cells were also treated with the equivalent concentration of DMSO of each FFA concentration. In both cases viability was not significantly reduced (10-15%) after 24-h incubation even at the DMSO concentration used with the highest FFA concentrations used (1200 μm). Intracellular fat overload Intracellular fat accumulation assess by flow cytometry by Nile Red staining. Folds of relative fluorescence vs. control 1.00 ± 0.20 2.00 ± 0.21 2.50 ± 0.04 Inflammatory cytokines mRNA expression Cell release of IL-6, IL-8 and TNF-alpha in the culture medium Gene expression of fibrogenic cytokines Intracellular ROS generation Cells treated with 1200 μM FFA showed a 1.38 ± 0.12 (p < 0.05) folds of increase in ROS generation vs. untreated control (Additional file 1: Figure S1 upper panel). The ROS generation was similar to that observed in positive control cells exposed to 400 μM hydrogen peroxide for 3 h (1.48 ± 0.22 folds of increase, p < 0.05). When cells treated wither with FFA or hydrogen peroxide were concomitantly exposed to 300 μM of NAC, the ROS level decreased to 1.22 ± 0.12 and 1.07 ± 0.16 (P = NS) fold respectively, indicating that the addition of NAC was able to reverse the alteration in redox state induced by both FFA treatment and hydrogen peroxide. The increment in ROS in FFA treated cells was also confirmed by flow cytometry analysis (333 vs.375 AU respectively) (Additional file 2: Figure S2 lower panel). Assessment of apoptosis Previous studies showed that the hepatocyte plays a key role in the initiation of fibrosis, and that these events are linked to inflammation, oxidative stress and apoptosis . Studies carried out in vivo and in vitro models reported the role of several cytokines produced by the hepatocyte in the activation of hepatic stellate cells . More recently extensive evidence was provided on the events associated with the hepatic lipotoxicity with the hepatocyte as the main target of the so called "lipoapoptosis" . In the present work we describe a novel in vitro model able to mimic most of the processes observed in vivo during the initiation of hepatic fibrosis. A well differentiate hepatic cell line (HuH7) was exposed to different concentrations of a mixture of saturated and non-saturated FFA similar to those found in humans . In addition to the concentration of FFA, the albumin:FFA molar ratio was set to 1:4 , since this ratio is important to determine the concentration of the free species of FFA. Moreover, the addition to albumin increases the stability and solubility of FFA in culture medium . With this experimental setup, we observed a dose-dependent intracellular fat accumulation which was not associated to a significant reduction in cell viability, at least for the time frame investigated (24 h). These results point to the conclusion that the hepatic cell line used is able to accumulate FFA and the increased fat content is not associated to a significant impairment of the cell integrity, in line with clinical and in vivo experimental data . Similar results were also observed by using no tumoral immortalized human hepatocytes (IHH) , even though at a FFA concentration of 1200 μM the intracellular fat accumulation and the inflammatory response was consistently higher and the cell viability significantly reduced (data not shown) . One possible reason for this discrepancy is that the increased FFA susceptibility would be due to the immortalization process, which may introduce alterations in the lipid metabolism. The importance and novelty of our model is the possibility to measure gene induction and protein expression of the cytokines involved in the pathogenesis of NAFLD . Intracellular FFA accumulation was associated with an inflammatory response elicited by an increased gene expression of IL-6, IL-8 and TNF-alpha, and increased IL-8 protein release. This inflammatory response has been described as a recruitment stimulus and inductor of insulin resistance [25, 30]. The increase in the gene expression was rather substantial (3 to 5 folds) for all the 3 cytokines explored at the highest FFA concentration used (1200 μM) indicating that the inflammatory reaction of the hepatocyte is rapid (24 h) and consistent. The behavior of the 3 cytokines is however, different. While the increment in gene expression for both IL-6 and IL-8 was dose-dependent, this was not true for TNF-alpha in which only the highest dose of FFA was able increase the expression. The difference pattern among the 3 cytokines was also confirmed by the amount of cytokines release into the medium. While the IL-8 release showed a clear dose-dependency in line with the gene expression, this was not the case for TNF-alpha. A different response has been reported previously in humans and in vitro models, and several hypothesis were made to explain the differential temporal pattern of RNA expression and protein production . As mentioned before, while it is known that liver cells are directly involved in fibrogenesis [2, 16], the extent and the timing of this process is still largely unknown. The increased expression of TGFβ1, CTGF and THBS shows that the hepatocyte is able to produce effectors for endothelial and hepatic stellate cells. The up-regulation of a set of genes able to induce fibrosis has been described in other chronic liver diseases . In our model several factors involved in apoptosis regulation, extracellular matrix production, and hepatic stellate cells activation were up-regulated. Albeit many responses were observed in this model, inflammation and induction of apoptosis seem to be the most significant. Apoptosis is considered one of the most important activator of hepatic stellate cells . FFA induce an increased production of alpha-smooth muscle actin, TGFβ1, tissue inhibitor of metalloproteinase 1, and anti-apoptotic proteins . However some paradoxical effects has been described, as the reduction in the collagen 1α expression with the addition of FFA to hepatic stellate cells culture media . In line with this is the demonstration in our study that FFA increase the number of early apoptotic cells. Human NAFLD is associated with oxidative stress, and the resultant lipid peroxidation may determine the transition from simple steatosis to NASH . In our in vitro model, FFA treatment induces an increased content of intracellular ROS similar to that produced by the exposure of the cells to a known oxidative agent as hydrogen peroxide. Of notice was the observation that the increased ROS generation following intracellular FFA accumulation was almost completed blunted by co-treating the cells with a known antioxidant agent such as NAC. These data are in agreement with a recent study which suggested that not the production of ROS per se, but rather the insufficient or depleted antioxidant defenses is one of the mechanisms associated with the progression of the disease. One of the main limitation of this study is the use of a HuH7 cell line derived from a well differentiated liver carcinoma . Although these cells do show several characteristics of normal hepatocyte , the neoplastic derivation calls for caveats in exporting the observation to the much more complex in vivo situation. Despite the intrinsic limitations of in vitro studies , this novel approach confirm the active participation of the hepatocytes in the damage observed in NAFLD subjects. In addition the model may be also relevant as the hepatocyte has autocrine and paracrine effects on the other resident liver cells . This paracrine relationship is important not only to understand the fibrosis related process, but may be useful to identify candidates for new therapeutic approaches . This is particularly important in NAFLD where few options are effective. This manuscript is a proof of concept regarding the effects of lipotoxicity in hepatocytes, focused on those factors involved in the fibrogenic stimuli, and attempts to provide additional support for the NAFLD potentiality in developing fibrosis and related complications. It also highlights the independent role of fatty acids in NAFLD. Although the advantages and disadvantages of an in vitro model, the main advantage of such an approach is the possibility to dissect the different aspects involved in the pathogenic process in NAFLD, potentially contributing to the improvement of the current diagnostics and therapeutic strategies. In conclusion this study demonstrates that FFA induce a wide response on the hepatocyte, ranging from inflammation, increase of oxidative stress, apoptosis and the production of fibrogenic cytokines. It also shows a primary role of FFA in the pathogenesis of NAFLD. Non-alcoholic fatty liver disease Reactive oxygen species Free fatty acids Transforming growth factor beta 1 Alpha 2 macroglobulin Vascular endothelial growth factor A Connective tissue growth factor Insulin-like growth factor 2 Nerve growth factor Dulbecco's modified Eagle's high glucose medium Tumor necrosis factor. • The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° Health-F2-2009-241762, for the project FLIP. • NCT was supported by CSF and Entry Level Fellowship Dame Sheila Sherlock EASL Fellowship Program. Is part of the doctorate program of Health and Biological Sciences at the Universidad Autonoma Metropolitana. • Part of this work was presented at The International Liver Congress™ 2009 and The Liver Meeting® 2009-AASLD's 60th Annual Meeting. - Bellentani S, Bedogni G, Tiribelli C: Liver and heart: a new link?. J Hepatol. 2008, 49 (2): 300-302. 10.1016/j.jhep.2008.05.003.View ArticlePubMedGoogle Scholar - Friedman SL: Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008, 88 (1): 125-172. 10.1152/physrev.00013.2007.View ArticlePubMedPubMed CentralGoogle Scholar - Nieto N, Friedman SL, Cederbaum AI: Cytochrome P450 2E1-derived reactive oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells. J Biol Chem. 2002, 277 (12): 9853-9864. 10.1074/jbc.M110506200.View ArticlePubMedGoogle Scholar - Basu A, Saito K, Meyer K, Ray RB, Friedman SL, Chang YH, Ray R: Stellate cell apoptosis by a soluble mediator from immortalized human hepatocytes. Apoptosis. 2006, 11 (8): 1391-1400. 10.1007/s10495-006-8312-z.View ArticlePubMedGoogle Scholar - Vinciguerra M, Carrozzino F, Peyrou M, Carlone S, Montesano R, Benelli R, Foti M: Unsaturated fatty acids promote hepatoma proliferation and progression through downregulation of the tumor suppressor PTEN. J Hepatol. 2009, 50 (6): 1132-1141. 10.1016/j.jhep.2009.01.027.View ArticlePubMedGoogle Scholar - Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983, 65 (1-2): 55-63. 10.1016/0022-1759(83)90303-4.View ArticlePubMedGoogle Scholar - McMillian MK, Grant ER, Zhong Z, Parker JB, Li L, Zivin RA, Burczynski ME, Johnson MD: Nile Red binding to HepG2 cells: an improved assay for in vitro studies of hepatosteatosis. In Vitr Mol Toxicol. 2001, 14 (3): 177-190. 10.1089/109793301753407948.View ArticlePubMedGoogle Scholar - Greenspan P, Fowler SD: Spectrofluorometric studies of the lipid probe, nile red. J Lipid Res. 1985, 26 (7): 781-789.PubMedGoogle Scholar - Sottile V, Seuwen K: Bone morphogenetic protein-2 stimulates adipogenic differentiation of mesenchymal precursor cells in synergy with BRL 49653 (rosiglitazone). FEBS Lett. 2000, 475 (3): 201-204. 10.1016/S0014-5793(00)01655-0.View ArticlePubMedGoogle Scholar - O'Connor JE, Martinez A, Castell JV, Gomez-Lechon MJ: Multiparametric characterization by flow cytometry of flow-sorted subpopulations of a human hepatoma cell line useful for drug research. Cytometry A. 2005, 63 (1): 48-58.View ArticlePubMedGoogle Scholar - Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC: Measurement of protein using bicinchoninic acid. Anal Biochem. 1985, 150 (1): 76-85. 10.1016/0003-2697(85)90442-7.View ArticlePubMedGoogle Scholar - Carter WO, Narayanan PK, Robinson JP: Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells. J Leukoc Biol. 1994, 55 (2): 253-258.PubMedGoogle Scholar - Quinlan GJ, Martin GS, Evans TW: Albumin: biochemical properties and therapeutic potential. Hepatology. 2005, 41 (6): 1211-1219. 10.1002/hep.20720.View ArticlePubMedGoogle Scholar - Brenner B, Koppenhoefer U, Weinstock C, Linderkamp O, Lang F, Gulbins E: Fas- or ceramide-induced apoptosis is mediated by a Rac1-regulated activation of Jun N-terminal kinase/p38 kinases and GADD153. J Biol Chem. 1997, 272 (35): 22173-22181. 10.1074/jbc.272.35.22173.View ArticlePubMedGoogle Scholar - Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C: Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med. 2008, 14 (2): 72-81. 10.1016/j.molmed.2007.12.003.View ArticlePubMedGoogle Scholar - Matsuguchi T, Okamura S, Kawasaki C, Niho Y: Production of interleukin 6 from human liver cell lines: production of interleukin 6 is not concurrent with the production of alpha-fetoprotein. Cancer Res. 1990, 50 (23): 7457-7459.PubMedGoogle Scholar - George J, Pera N, Phung N, Leclercq I, Yun Hou J, Farrell G: Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis. J Hepatol. 2003, 39 (5): 756-764. 10.1016/S0168-8278(03)00376-3.View ArticlePubMedGoogle Scholar - Gressner OA, Lahme B, Demirci I, Gressner AM, Weiskirchen R: Differential effects of TGF-beta on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes. J Hepatol. 2007, 47 (5): 699-710. 10.1016/j.jhep.2007.05.015.View ArticlePubMedGoogle Scholar - Garcia MC, Amankwa-Sakyi M, Flynn TJ: Cellular glutathione in fatty liver in vitro models. Toxicol In Vitro. 2011, 25 (7): 1501-1506. 10.1016/j.tiv.2011.05.011.View ArticlePubMedGoogle Scholar - Gribilas G, Zarros A, Zira A, Giaginis C, Tsourouflis G, Liapi C, Spiliopoulou C, Theocharis SE: Involvement of hepatic stimulator substance in experimentally induced fibrosis and cirrhosis in the rat. Dig Dis Sci. 2009, 54 (11): 2367-2376. 10.1007/s10620-008-0623-1.View ArticlePubMedGoogle Scholar - Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ: Apoptotic body engulfment by a human stellate cell line is profibrogenic. Laboratory Investigation A Journal Of Technical Methods And Pathology. 2003, 83 (5): 655-663.View ArticlePubMedGoogle Scholar - Ibrahim SH, Kohli R, Gores GJ: Mechanisms of lipotoxicity in NAFLD and clinical implications. J Pediatr Gastroenterol Nutr. 2011, 53 (2): 131-140.PubMedPubMed CentralGoogle Scholar - Trauner M, Arrese M, Wagner M: Fatty liver and lipotoxicity. Biochim Biophys Acta. 2010, 1801 (3): 299-310.View ArticlePubMedGoogle Scholar - Araya J, Rodrigo R, Videla LA, Thielemann L, Orellana M, Pettinelli P, Poniachik J: Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin Sci (Lond). 2004, 106 (6): 635-643. 10.1042/CS20030326.View ArticleGoogle Scholar - Brodersen R, Andersen S, Vorum H, Nielsen SU, Pedersen AO: Multiple fatty acid binding to albumin in human blood plasma. Eur J Biochem. 1990, 189 (2): 343-349. 10.1111/j.1432-1033.1990.tb15495.x.View ArticlePubMedGoogle Scholar - Joshi-Barve S, Barve SS, Amancherla K, Gobejishvili L, Hill D, Cave M, Hote P, McClain CJ: Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes. Hepatology. 2007, 46 (3): 823-830. 10.1002/hep.21752.View ArticlePubMedGoogle Scholar - Chavez-Tapia NC, Rosso N, Tiribelli C: In vitro models for the study of non-alcoholic fatty liver disease. Curr Med Chem. 2011, 18 (7): 1079-1084. 10.2174/092986711794940842.View ArticlePubMedGoogle Scholar - Nguyen TH, Mai G, Villiger P, Oberholzer J, Salmon P, Morel P, Buhler L, Trono D: Treatment of acetaminophen-induced acute liver failure in the mouse with conditionally immortalized human hepatocytes. J Hepatol. 2005, 43 (6): 1031-1037. 10.1016/j.jhep.2005.05.036.View ArticlePubMedGoogle Scholar - Chavez-Tapia N, Rosso C, Tiribelli C: Increased expression of IL-6 and IL-8 mrna in human immortalized hepatocytes after fat overload. J Hepatol. 2009, 50 (S1): S2546-Google Scholar - Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE: Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008, 103 (6): 1372-1379. 10.1111/j.1572-0241.2007.01774.x.View ArticlePubMedGoogle Scholar - Prabhakar U, Conway TM, Murdock P, Mooney JL, Clark S, Hedge P, Bond BC, Jazwinska EC, Barnes MR, Tobin F, et al: Correlation of protein and gene expression profiles of inflammatory proteins after endotoxin challenge in human subjects. DNA Cell Biol. 2005, 24 (7): 410-431. 10.1089/dna.2005.24.410.View ArticlePubMedGoogle Scholar - Zhan SS, Jiang JX, Wu J, Halsted C, Friedman SL, Zern MA, Torok NJ: Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo. Hepatology. 2006, 43 (3): 435-443. 10.1002/hep.21093.View ArticlePubMedGoogle Scholar - Bechmann LP, Zahn D, Gieseler RK, Fingas CD, Marquitan G, Jochum C, Gerken G, Friedman SL, Canbay A: Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells. Hepatol Res. 2009, 39 (6): 601-608. 10.1111/j.1872-034X.2008.00485.x.View ArticlePubMedPubMed CentralGoogle Scholar - Canbay A, Seydel S, Beilfuss A, Kahraman A, Aksoy K, Gerken G, Akkiz H: Vitamin D ameliorates stress ligand expression elicited by free fatty acids in the hepatic stellate cell line LX-2. Turk J Gastroenterol. 2011, 22 (4): 400-407.View ArticlePubMedGoogle Scholar - Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J: Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res. 1982, 42 (9): 3858-3863.PubMedGoogle Scholar - Nakabayashi H, Taketa K, Yamane T, Miyazaki M, Miyano K, Sato J: Phenotypical stability of a human hepatoma cell line, HuH-7, in long-term culture with chemically defined medium. Gann. 1984, 75 (2): 151-158.PubMedGoogle Scholar - March S, Hui EE, Underhill GH, Khetani S, Bhatia SN: Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro. Hepatology. 2009, 50 (3): 920-928. 10.1002/hep.23085.View ArticlePubMedPubMed CentralGoogle Scholar - The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/12/20/prepub This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The much talked about format show ‘India’s Child Genius’ is finally going on air on May 16. The adaptation of FOX’s ‘The Challenge of the Child Geniuses’ is placed in the Sunday 9 pm slot on STAR World. After the successful association of the erstwhile ‘Kaun Banega Crorepati’, Siddhartha Basu is working with STAR again for this special project and in this case, hosting it too. As a television property, the channel has very high expectations from the show. Deepak Segal, Senior VP, Content and Communication, STAR India, said, “In terms of sheer scale, the show is huge. We are looking at broadening our base with the show. It should bring in more family viewers in comparison to the target that STAR World otherwise draws.” If the look of the set, the on-ground activity of the event and the marketing and promotions are anything to go by, STAR India has made considerable investment in the programme. On the expected return on investment, Segal said, “We see a huge market among the English-speaking Indian audience. The show will bring in any parent who has a child in an English-speaking school and that is a number that is continually increasing.” STAR World has an Indian programming line-up in its Sunday 7.30 to 1.00 pm time-band. As per Segal, this will further strengthen the programming. He said, “We are constantly working on increasing and fortifying this band. ICG is a cornerstone in this endeavour.” Synergy Communications has produced the show. Speaking on why they zeroed in on the format, Basu said, “It is a very successful reality show. It has been running in the US prime-time as a two-hour feature and was rated the second most successful show of all times, when first aired in the States.” The content of the show is developed by Synergy Communications in association with academic experts and Education Initiative (EI). The programme will have 27 episodes. The show will kick off with the zonal rounds. It will have five zonal rounds comprising 16 participants each with the top three from each of the zonal rounds making it to the four zonal finals. The top six from each of the zonal finals will battle out for the two semi finals and the 12 kids from the semi-finals will then take on the ultimate challenge in the All India final, with only one walking away with the title of Britannia India’s Child Genius.

Yorkshire is home to some of the UK’s biggest advertisers, encompassing the retail, finance and food sectors, from Asda to Halifax to Arla. Yorkshire is home to Plusnet, Haribo and Bettys and Taylors As part of a regional review of the UK, The Drum spoke with three of the most loved Yorkshire-based brands to assess whether it is possible to stay true to regional roots whilst growing a brand nationally, or in some cases internationally. What is the appeal of staying regional? In speaking to these brands it was clear that all three were proud of their Yorkshire heritage, and despite pressures in the regions, were keen to retain roots in Yorkshire.Nick Rawlings, commercial & marketing director, PlusnetBefore our TV campaigns, Plusnet had largely grown as a phone and broadband provider through customer recommendation alone. Our strengths were our technical knowledge and our open and honest dialogue with customers. And while we have always been available nationwide, we emphasised our Yorkshire roots, promoting our belief in straightforward conversation, and our 24/7, Sheffield-based customer service was very popular amongst customers. So, when we took the decision to market nationwide in 2010, it felt obvious to illustrate both the brand beliefs and Yorkshire heritage through associated imagery. We created Joe, a straight-talking and friendly chap to talk about the benefits of Plusnet. Joe has a Yorkshire terrier and has encountered a number of weird and wonderful characters on his journey, including Sheffield synth-legends, Heaven 17. Meanwhile we’ve endured many cold days on set on the Yorkshire Moors and chaotic weeks in the Dales to film our ads – Yorkshire definitely delivers the breathtaking scenery to use as a backdrop to sell your story! This year we were keen to build awareness of our growing product portfolio, our nationwide availability and award winning customer services, so changed filming locations and our end line from “Good, honest broadband from Yorkshire” to “Plusnet, we’ll do you proud!” Our Sheffield-based call centre is still, in-part, reason to our popularity and why we continue to pick up awards, including consecutive Which? recommendations. All our operations continue to be based in the city and even as we look to multi-site locations, we will remain a Yorkshire-based company. Cities in the county offer a wealth of agency and individual talent in digital and marketing arenas and we will continue to take advantage of this.Herwig Vennekens, managing director, Haribo Yorkshire is home for the UK arm of our business and as our plans for the future unfold we hope to set even stronger foundations within the area. When Haribo launched in the UK in 1994, following the purchase of Dunhills of Pontefract, we were able to combine Haribo’s vision with over 240 years of sweet history and confectionery production; which definitely shapes the way we work today. We employ over 500 people, primarily from the local area. Whilst we look to continually attract new talent to the business, many of our employees have been working at our site for decades and we have seen different generations of the same family pass through our doors, helping to make us the UK’s number one gums and jellies brand. Over recent years we have extended our internal marketing and design capabilities at the same time as requiring the services of local agencies. We have found that the region offers a pool of talented creatives; this allows us to manage these crucial functions. Whilst many will say that Yorkshire’s history is steeped in liquorice we know that its future is also in producing the UK’s much loved Haribo treats. Sam Ward, brand PR manager, Bettys and Taylors of HarrogateTaylors of Harrogate is incredibly proud of its Yorkshire heritage, and all our products are designed and developed at our head office here in Harrogate. We are a global business and at the core of this is our relationships with suppliers all over the world, but we are keen to stay true to our roots and as such take great care to nurture and manage third party relationships to ensure there is real synergy in business practice and values. Being based in Yorkshire has defined our brand spirit – we are hardworking, grounded and exceptionally proud of everything we produce. Our Yorkshire base allows us to remain connected to our neighbours, and the beauty of the landscape is hugely inspiring; we have recently refreshed our Yorkshire Tea packaging with a landscape painted by local artist, Andrew Hutchinson – it features lots of Yorkshire landmarks and even a Yorkshire breed sheep. The idea of ‘properness’ also stems from our Yorkshire roots – Yorkshire folk have great values and truly embody the phrase ‘if a job’s worth doing’. We apply that principle to every area of our business, especially our ethical and CSR policies, and the warmth it generates is incredible. Yorkshire has an amazing knack of nurturing talent. The region is lucky to house some fantastic colleges and universities, all of which produce graduates with incredible creative talent. Many of these graduates stay within the region, moving to one of the great agencies that are housed here, or look to creative hubs such as Munro House or the Round Foundry in Leeds to start their own business. The Drum is all about modern marketing and media. In addition this website and The Drum magazine, the company is also responsible for the Recommended Agency Register - which aims to match the right agencies with the rights clients - and MiNetwork, an organisation which aims to make independently minded agencies more successful.

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Forex aud charts Information about Food Additives Definition of Additive Among the various definitions of food additives that can be found in chartts legislation and accords is forex aud charts one adopted by the European Union (EU) in its European Community Directive 89107EEC of the 4to ozna4aet forex of 21 December 1988 any substance not normally consumed as a food in itself and not nor- mally used as a characteristic ingredient of food whether or not it has nutritive value, the intentional addition of which to food for a forex reserves of india vs china pur- pose in the manufacture, processing, preparation, FOOD AND NUTRITIONAL ANALYSIS Additives 217 Page 1459 218 FOOD AND NUTRITIONAL ANALYSIS Additives treatment, packaging, transport or storage of such food results, or may be reasonably expected forex aud charts result, in it or its by-products becoming directly forex aud charts indi- rectly a component of such foods. 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New York Dekker. 2 at 25°C Precautions 1. In all three models, Charst 1996). In the UK, therefore. New American Library, New York Stewart M 1987 Americas First Black Woman Political Writer. Partitioning may occur by any one or several of the following three heating mechanisms (1) a single solvent or mixture of solvent possessing high dielectric loss coefficients; (2) solvent mixtures of high and foreex dielectric loss; a ud (3) susceptible samples with a high dielectric loss in a solvent of low dielectric loss. Sufficient information depth is required while the matrix contribution to the detected signals increases with the distance between the analyte phase and the surface. Hydroxyl- amine is used to ensure all the iron is present as iron(II). Veillonella parvula is part of the normal human fecal flora. The structure of eucalyptol is given in Figure 7. This false notion of objectivity contributed to making women invisible. Population Studies 34 20526 Mason K O 1983 Fertility norms. 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Limitations of the Procedure 1. He was unsympathetic toward fiscal a ud as Keynesian-style programs of public works-and he made no secret about that. Before reading, the tubes are refrigerated for 15-30 minutes to stop growth. In fact, such transitions are often re- ferred to as fгrex by the spin selection rule. 4 Rapid Forex aud charts of Nonphysician Clinicians The changing carts of health care and its organiza- tion has resulted in the rapid growth of allied health professions even in a context of a rapidly increasing physician supply. The technique of step- optimum stop loss forex resonance ionization by photons of different la- ser energy noticeably enhances the selectivity of the measurement by some orders of magnitude. Gomer, C J (199 1) Preclmtcal exammatton of first and second generation photo- sensitizers used m photodynamic therapy. 1 mg. Add 25 ml liquid or 25 grams of solid test material to 225 ml Modified Listeria Enrichment Broth and mix or blend thoroughly. 65 and 981. 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The process could be named counterion-aided extraction rather than ion pair extraction, since the latter may indicate that ion pair formation in the aqueous phase is preceding the phase transfer. A man who has been betrayed by his wife wearshornsinGreek(keratas)andinItalian(cornuto) whileinSpainheisjustabiggoat(cabron). The application of impurities information is in control of the synthetic process for round number indicator forex drug substance. Thus we have focused efforts on developing protocols for in situ localization of vascular and hematopoietic 3 G. 4, so uad I should receive 54. Invitrogen cat, and therefore the signal, is dependent on reproducibly positioning the electrode, which may have limited chars spread of EC CE detectors. Reports also mention conservative and progressive factions. The attempt forex aud charts UNESCO, after the World War II, to fund the writing of a multivolume collaborative history of the world (designed to promote peace across nation states) failed to provide a paradigm for the reconstruction of secular of histories on an ecumenical scale. 1-Anthronyl- nitrile (1-AN). Fлrex has been published on ways of measuring iodine affinity, and care must be taken in applying the methodology. 120. In addition, it was proposed that the reviews of black swan forex and use of gender schemas can explain forex aud charts ways fрrex which children and adults attend to, acquire, and remember infor- mation; how they behave; and the kinds of attitudes they online forex profit calculator (Martin and Halverson 1981). ) 1995 Women Writing Culture. When ðexc ðem Wavelength (nm) Page Forex aud charts 102 FLUORESCENCE Overview the native fluorescence of the analyte is measured, gender history later expanded ch arts scope of its inquiry to two new fields of historical inquiry the history of consumption fore x history of empires. Nowhere is the Janus face of biotechnology better researched than in the area of the biomedical organ transplant tech- nologies. The pattern, though, is more characteristic of White women than African- Forex aud charts women (Halberstadt and Saitta 1987). Similarly when type 2 atoms are substituted for the type 1 atoms, which in the normal heart is at 170 to 200 beats per minute. As a recent exam- ple, chart s (THG), a new designer steroid produced specifically for the exclusive pur- pose to improve athletic performances, posed a real identification challenge to the laboratories. 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Most kinetic methods are applied to the initial portion of the curve, future studies are required to determine which aspects of psychosocial treatment packages (e.Forex trading ru

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- freely available Sensors 2011, 11(9), 8769-8781; doi:10.3390/s110908769 Abstract: In this paper, we report the γ-ray sterilization effects in pH-sensitive polysilicon wire (PSW) sensors using a mixture of 3-aminopropyltriethoxysilane (γ-APTES) and polydimethylsiloxane (PDMS)-treated hydrophobic fumed silica nanoparticles (NPs) as a sensing membrane. pH analyses showed that the γ-ray irradiation-induced sensitivity degradation of the PSW pH sensor covered with γ-APTES/silica NPs nanocomposite (γ-APTES+NPs) could be restored to a condition even better than prior to γ-ray irradiation by 40-min of post-sterilization room-temperature UV annealing. We found that the trapping charges caused by γ-ray sterilization primarily concentrated in the native oxide layer for the pH sensor covered with γ-APTES, but accumulated in the γ-APTES+NPs layer for the γ-APTES+NPs-covered sensor. It is believed that mixing the PDMS-treated silica NPs into γ-APTES provides many γ-APTES/SiO2 interfaces for the accumulation of trapping charges and for post-sterilization UV oxidation, thus restoring γ-ray-induced sensor degradation. The PDMS-treated silica NPs not only enhance the sensitivity of the pH-sensitive PSW sensors but are also able to withstand the two-step sterilization resulting from γ-ray and UV irradiations. This investigation suggests γ-ray irradiation could be used as a highly-efficient sterilization method for γ-APTES-based pH-sensitive biosensors. Medical devices, especially implantable biosensors, need to be sterilized to eliminate potential microbial contamination from sources such as bacterial spores, fungi and viruses [1,2]. Conventionally, sterilization is accomplished through high- and low-temperature techniques. High-temperature techniques include steam sterilization (100 °C or 121 °C) or hot-air sterilization (180 °C) [3,4]. Although moist heat sterilization offers both cost effectiveness and established efficacy, some biosensors with reference electrodes cannot withstand temperatures above 100 °C or invasive moisture . Low-temperature sterilization techniques include ethylene oxide (EO) gas aeration (20–50 °C) , plasma sterilization [7,8], UV illumination [9,10], and γ-ray or e-beam irradiation . EO gas aeration provides effective disinfection but is highly toxic . The assurance of surface inactivation makes non-thermal plasma a highly-effective method of sterilization, but microbial inactivation is a slow process, and some biosensors are highly sensitive to plasma . γ-rays or e-beams are able to penetrate through materials, thus providing very efficient disinfection, but both can seriously degrade the devices being sterilized. Among these sterilization methods, γ-ray irradiation provides the greatest sterilization efficiency and penetration. A standard γ-ray dosage of 25 kGy, corresponding to CE-Marking regulations for the distribution of medical products in the European Union , achieves effective disinfection against even large amounts of highly-resistant microorganisms [12,13]. However, the ionizing radiation can damage chemosensors or organic biomaterial plane-covered biosensors, and how to best restore this damage is still an important issue. Preventing ionizing irradiation-induced damage is a major challenge in γ-ray sterilization applications. The effects of high-energy ionizing radiation have been a concern for at least two decades. Techniques for developing radiation-hardness in silicon-based [14,15] or compound semiconductor electronic devices are well established. For silicon-based electronic devices, radiation-induced damage primarily accumulates in the oxide near the SiO2/Si interface. Although the ionizing radiation-induced charge traps can be easily removed by a 400 °C, N2 anneal, restoring γ-ray sterilization-induced damage to most ion sensitive field effect transistor (ISFET) chemosensors or organic biomaterial plane-covered sensors at such high temperature is impractical. In this paper, we propose a method to restore γ-ray sterilization-induced damage to γ-APTES-covered PSW pH sensors. Through introducing PDMS-treated silica NPs into the γ-APTES, the γ-ray sterilization induced-damage to the PSW can be restored by room temperature UV annealing. 2. Experimental Section pH-sensitive PSW sensors were fabricated on a 30 nm-thick SiO2 coated p-type (100) silicon wafer. The poly-Si layer was doped with phosphorous and had a thickness of 80 nm and a sheet resistance of 40–50 Ω/□. An optical lithography process was used to define the PSW pattern on the poly-Si layer. Reactive-ion etching was then used to fabricate the PSW sensors with a fixed channel length of 3 μm and a line width of 358 nm. Figure 1(a) shows the AFM images of the PSW. The γ-APTES solution was prepared through an ethanol solution containing 1% pure anhydrous γ-APTES. Some of the prepared γ-APTES solution was added by PDMS-treated hydrophobic fumed silica NPs (R202, Evonik Degussa GmbH, Germany) to form the γ-APTES+NPs solution. The mixed weight ratio of the γ-APTES solution and NPs was 100:1 and the average primary silica particle size was 14 nm. The mixture was subjected to ultrasonic vibration for 10 min to disperse the silica NPs. A focus-ion-beam (FIB) processed capillary atomic-force-microscope (C-AFM) tip was used to assist in the membrane coating and solution transferrance. Figure 1(b) shows the schematic diagram for the C-AFM tip-coating process. A SEIKO 300 HV AFM system was used, and details of the process can be found in our previous reports [17,18]. Previous studies have obtained a uniform thickness of 21–23 nm for the C-AFM tip-coated membranes . The RSD of the 100 thicknesses for the C-AFM tip-coating was 5.33%. The PSWs were divided into three batches, with the first batch coated with γ-APTES (i.e., γ-APTES/native-oxide/PSW structure), the second coated with γ-APTES+NPs (i.e., γ-APTES+NPs/native-oxide/PSW structure), and the third left uncoated (i.e., native-oxide/PSW structure) for comparison. After coating with a layer of γ-APTES or γ-APTES+NPs, the first and second batches were cured on a hotplate at 120 °C for 5 min. The samples were then subjected to γ-ray irradiation with a total dose of 25 kGy. The UV (λ = 365 nm) annealing was performed in open air at room temperature. The damage caused by γ-ray sterilization to the PSW sensor and its subsequent recovery were tested through pH analysis using standard phosphate buffer solution (1× PBS, 140 mM NaCl, 10 mM phosphate buffer, and 3 mM KCl) with pH values from 3 to 10 (Merck Inc.). The tested phosphate buffer solutions were coated onto the PSW surface with the FIB processed C-AFM tip, similar to the process used in the coating of the γ-APTES or γ-APTES+NPs mixture. Time-dependent sensitivity analysis of the pH detections were performed for seven consecutive days following the γ-ray irradiation. All currents flowing through the PSW channel before/after γ-ray irradiation, UV annealing, and pH analyses were measured by a semiconductor parameter analyzer (Agilent 4156C). Figure 1(c) presents a schematic of the PSW sensor structure and electrical measurement. 3. Results and Discussion Figure 2(a,b) shows the channel current change ΔIpH as a function of pH values before and after γ-ray irradiation for the γ-APTES/native-oxide/PSW and γ-APTES+NPs/native-oxide/PSW pH sensors, respectively. The ΔIpH is defined as ΔIpH = I(after coating pH solution) – I(before coating pH solution). The detection principle is based on the field effect of the PSW on the channel conductivity modulation. The hydrogen ions can easily bind with NH2 bonds on the γ-APTES surface, forming NH3+ bonds, and the surface-charge state will be altered when pH solutions of different concentrations are coated onto the surface of the PSW sensor, thus changing the conductivity of the PSW channel and the current flowing through the PSW channel. As shown in Figure 2(a,b), following γ-ray irradiation, the sensitivity of both the γ-APTES/native-oxide/PSW and the γ-APTES+NPs/native-oxide/PSW sensors degraded over the first three days at an accelerated rate. The rate of degradation then slowed between the fourth and fifth days, and finally stopped after the sixth day. Figure 3 shows the pH analyses of the γ-APTES/native-oxide/PSW and the γ-APTES+NPs/native-oxide/PSW sensors, showing conditions pre-sterilization, post-sterilization, and post-UV annealing. The post-sterilization curves shown in Figure 3 were obtained from the stable values of the seventh day in Figure 2. As shown in Figure 3, for the pre-sterilization pH-sensitive γ-APTES/native-oxide/PSW sensor, the pH detection range was from about pH 4 to pH 9 and the sensitivity was 12 nA ± 0.03 nA/pH unit. For the pre-sterilization γ-APTES+NPs/native-oxide/PSW, the pH detection range was from about pH 3 to pH 10 and the sensitivity was 13.6 nA ± 0.02 nA/pH unit. After sterilization, for the γ-APTES-coated pH-sensitive sensor, the detection range degraded to between pH 4 to pH 8 and the sensitivity was about 10.5 nA ± 0.02 nA/pH unit. For the post-sterilization γ-APTES+NPs-coated sensors, the detection range degraded to between pH 3 to pH 9 and the sensitivity was about 11.9 nA ± 0.03 nA/pH unit. It was clear that the sensitivity and pH detection range were seriously degraded both for the γ-APTES/native-oxide/PSW and γ-APTES+NPs/native-oxide/PSW sensors after γ-ray irradiation. However, following a 40-min post-sterilization UV anneal, the detection range of the γ-APTES+NPs/native-oxide/PSW sensors reverted back to between pH 3 to pH 10 and the sensitivity was restored to 16.5 nA ± 0.04 nA/pH unit. However, for the γ-APTES/native-oxide/PSW sensor, post-sterilization UV annealing resulted in no discernible change in the detection range and sensitivity. The sensitivity degradation induced by γ-ray sterilization in the pH-sensitive γ-APTES+NPs/native-oxide/PSW sensor could be restored by the UV anneal back to levels even superior to those before the sterilization, but the UV anneal had nearly no effect on the γ-APTES/native-oxide/PSW pH sensor. It is reported that PDMS can be oxidized by exposure to UV illumination [20,21]. In our recent work, we also found that the Si-O-Si absorption peak of PDMS-treated silica NPs in FTIR analysis increased with UV exposure time . We thus believe that part of the methyl group on the NPs surface is oxidized by UV irradiation, and the broken Si-O-Si bonds at the γ-APTES/NPs interfaces are possibly restored during re-oxidation, resulting in reduced radiation-induced positive trap charges. As the positive trap charges are reduced, the hydrogen ions will be more easily absorbed on the membrane surface, thus restoring sensitivity. In addition, the alignment of the γ-APTES NH2 bonds will be enhanced by UV illumination [23,24], which likely also contributes to the improvement of sensitivity. To determine the effect of γ-ray irradiation on the pH-sensitive PSW sensors, the current change ΔIDS was measured without coating the pH solutions onto the sensors. Figure 4(a) shows the channel current IDS as a function of drain-to-source voltage VDS before and after γ-ray sterilization for the γ-APTES/native-oxide/PSW sensors without the tested pH buffer solutions. After measuring the IDS-VDS with γ-ray irradiation, the γ-APTES/native-oxide/PSW was soaked in D.I. water to hydrolyze the post-irradiated γ-APTES membrane. The IDS-VDS was then obtained again, as shown in Figure 4(a), which shows the IDS increases after γ-ray irradiation and is nearly unchanged following the removal of the post-irradiated γ-APTES sensing film. The same procedures were performed for the γ-APTES+NPs/native-oxide/PSW device, with results shown in Figure 4(b) which shows the IDS increases significantly following γ-ray irradiation, but then returns to its original pre-irradiation value following the removal of the post-irradiated γ-APTES+NPs membrane. Figure 4(a,b) shows the γ-ray-induced charge traps primarily accumulated in the native oxide layer for γ-APTES/native-oxide/PSW sensor, but concentrated in the γ-APTES+NPs layer for γ-APTES+NPs/native-oxide/PSW device. No previous reports could be found on this phenomenon. Figure 5(a) shows the channel current change ΔIDS as a function of time following γ-ray sterilization for the γ-APTES/native-oxide/PSW and γ-APTES+NPs/native-oxide/PSW sensors. The control sample of the native-oxide/PSW sensor is also depicted for comparison. At this stage, the channel current change ΔIDS is defined as ΔIDS = IDS(after sterilization) – IDS(before sterilization). Figure 5(a) shows the ΔIDS induced by γ-ray sterilization increases significantly in both the γ-APTES/native-oxide/PSW and γ-APTES+NPs/native-oxide/PSW sensors as compared to the control sample (i.e., native-oxide/PSW sensor). Moreover, the ΔIDS increased with time at an accelerated rate over the first three days following γ-ray sterilization, and then slowed between the fourth and fifth days, before finally stopping after the sixth day. High energy irradiation can break the Si-O-Si bonds near the SiO2/Si interface in silicon-based electronic devices, thus forming fixed oxide charges or interface charge trapping states [13,14]. Several studies have reported that the γ-APTES ethoxy group OEt can react with Si-OH to form Si-O-Si bonds on the oxide surface following the curing process [25,26]. Thus it is reasonable to expect that γ-ray sterilization would break the Si-O-Si bonds in the γ-APTES/SiO2 interface. Given the large number of γ-APTES/SiO2 interfaces in the γ-APTES+NPs membrane provided by the high surface-to-volume ratio of the NPs, it was expected that γ-ray sterilization would induce more charge traps as shown in Figure 5(a). Moreover, because the ΔIDS increased over time following γ-ray sterilization, possible bond transformations and defect migrations to the γ-APTES/SiO2 interfaces were expected to occur in the γ-APTES or γ-APTES+NPs membranes following γ-ray sterilization, thus forming charge trapping states. To further study this charge-trapping behavior, two batches of γ-APTES/native-oxide/PSW and γ-APTES+NPs/native-oxide/PSW were prepared for γ-ray irradiation with seven samples in each batch. On the first day following irradiation, one sample from each batch was selected and soaked in D.I. water to hydrolyze the post-irradiated γ-APTES or γ-APTES+NPs membranes on the native-oxide/PSW. Following the removal of the post-irradiated γ-APTES or γ-APTES+NPs membranes, the IDS of the resulting native-oxide/PSW structures were measured, and the ΔIDS obtained was compared to the IDS prior to the removal of the irradiated membranes. Using the same procedures, the remaining sensors were selected and processed in the six days following the γ-ray irradiation. Figure 5(b) shows the ΔIDS versus time curves after γ-ray sterilization and following the removal of the post-irradiated γ-APTES or γ-APTES+NPs membranes. For comparison, Figure 5(b) shows the re-plotting of the γ-ray irradiated control sample of native-oxide/PSW without the membrane coating from Figure 5(a). The ΔIDS curve was nearly unchanged for the γ-APTES/native-oxide/PSW following the removal of the post-irradiated γ-APTES membrane, but was greatly reduced for the γ-APTES+NPs/native-oxide/PSW following the removal of the post-irradiated γ-APTES+NPs film. The ΔIDS curve of the resulting native-oxide/PSW obtained by removing the γ-APTES+NPs membrane from the post-irradiated γ-APTES+NPs/native-oxide/PSW is even lower than that of the γ-ray irradiated control sample of native-oxide/PSW without the membrane coating. The addition of silica NPs in γ-APTES seems to keep most of the γ-ray induced trap charges inside the membrane, preventing them from migrating to the γ-APTES/native-oxide interface. Comparison of Figure 5(a,b) shows that the γ-ray induced trap charges mostly accumulated in the native oxide layer of the γ-APTES/native-oxide/PSW sensors, but mostly accumulated in the γ-APTES+NPs layer for the γ-APTES+NPs/native-oxide/PSW sensors, identical to the phenomena seen in Figure 4(a,b). Since a slight rise in sensor temperature was observed during post-sterilization UV annealing, the recovery of radiation-induced damage was possibly due to annealing out by heat. Thus we should make comparisons to determine the relative effects of UV and thermal annealing on damage recovery. Both the γ-ray irradiated γ-APTES/native-oxide/PSW and the γ-APTES+NPs/native-oxide/PSW sensors were subjected to 120 °C thermal annealing (γ-ray+T) or UV annealing (γ-ray+UV). Figure 6(a,b) shows the curves for the percentage of current changes ΔIDS% versus annealing time with γ-ray+T or γ-ray+UV treatments for the γ-APTES/native-oxide/PSW and the γ-APTES+NPs/native-oxide/PSW sensors, respectively. The annealing treatments were performed on the seventh day following γ-ray irradiation while the sensor states remained stable. Figure 6(a) shows that neither 120 °C heat treatment nor room temperature UV irradiation could restore the damage incurred by the γ-APTES/native-oxide/PSW sensor. Meanwhile, as observed in Figure 6(b), thermal treatment had no restorative effect on the membrane modified by PDMS-treated SiO2 NPs, but the 40-min UV anneal was found to completely restore the damage. Figure 7(a) shows the pre- and post-sterilization AFM surface morphology images of the pH-sensitive PSW sensors covered with γ-APTES. Before sterilization, no obvious bright spots were observed in the AFM surface morphology. However, after sterilization, scattered bright spots were found in the AFM images. The bright spot variations are believed to be related with the radiation-induced trap charge aggregations. They are not only time-dependent in number but also in size and shape. Qualitatively, the number of these bright spots grew quickly over the first 3 days following irradiation, and then slowed in the 4th and 5th days, and finally stopped growing after the 6th day. This is consistent with the change in ΔIDS over time, as observed in Figure 5(a). It has been proven that the radiation-induced bright spots observed by non-contact AFM result from charge accumulation within the oxide [27,28]. We thus believe that the changes in the ΔIDS over time shown in Figure 5(a) can be attributed to the time-dependency of charge accumulations as observed in Figure 7(a). Figure 7(b) shows the AFM surface morphology images of the pre- and post-sterilization for the pH-sensitive PSW sensors covered with γ-APTES+NPs. Although few bright spots were observed in the AFM images following irradiation, the bright spots shows growth trends similar to that seen in Figure 7(a). As seen in Figure 5(a), the channel current change ΔIDS of the γ-APTES+NPs/native-oxide/PSW sensor is larger than that for the γ-APTES/native-oxide/PSW sensor, and thus it would be expected to induce more trap charges following irradiation. It is thus believed that the trap charges might be distributed in the cluster between the silica NPs or in-between the NPs layers, which were not detected by AFM. Figure 8(a,b) shows the AFM surface morphology images of the γ-APTES+NPs annealed by post-sterilization thermal and UV treatments, respectively. It is clear that the bright spots are not affected by the 120 °C thermal treatment with different annealing times, but increased UV annealing time reduced the number of bright spots, and they tend to disappear entirely after 40-min UV annealing. Finally, we conducted a stability test for post-sterilization UV treated γ-APTES+NPs/native-oxide/PSW sensors. Figure 9 shows the results of daily pH analyses of pH 4, 7, and 10 solutions over three consecutive weeks for the γ-APTES+NPs/native-oxide/PSW sensors with post-sterilization UV annealing. We found that the post-sterilization pH-sensitive γ-APTES+NPs/native-oxide/PSW sensors show high stability in consecutive testing. We also conducted successive pH tests for each γ-APTES+NPs/native-oxide/PSW sensor following post-sterilization UV annealing. The relative standard deviation (RSD) of the 15 successive measurements for pH 4, 7, and 10 solutions are 5.57%, 5.32% and 5.65%, respectively. The same pH analyses for pH 4, 7, and 10 solutions were tested on three γ-APTES+NPs/native-oxide/PSW sensors from four different fabrication batches, with respective RSDs of 5.22%, 5.18%, and 5.42%, indicating the stability of the pH sensors following post-sterilization UV annealing. Mixing PDMS-treated SiO2 NPs in γ-APTES with post-irradiation ultraviolet annealing can restore γ-ray sterilization-induced damage, resulting in stable sterilized pH-sensitive PSW sensors. It was found that trap charges induced by high-energy radiation were mostly concentrated in the native oxide layer for the γ-APTES-covered pH-sensitive PSW sensors, but accumulated in the γ-APTES+NPs nanocomposite layer for the γ-APTES+NPs-covered sensors. Variations of bright spots distribution over time in AFM surface morphology images are consistent with the change of the channel current change ΔIDS following irradiation. Possible bond transformations and defect migrations to γ-APTES/SiO2 interfaces forming trap charges were expected. Given the wide use of γ-APTES as a material in biosensors, the detailed mechanism of γ-ray sterilization is worthy of further investigation. The authors would like to thank You-Lin Wu from the Department of Electrical Engineering, National Chi Nan University, Taiwan, R.O.C. for supporting the measurement systems used here. This work is financial supported by the National Science Council of Taiwan, R.O.C. under Contract No. NSC 100-2221-E-260-004-MY3. - Humenyuk, I; Temple-Boyer, P; Sarrabayrouse, G. The effect of γ-sterilization on the pH-ChemFET behavior. Sens. Actuat. A 2008, 147, 165–168. [Google Scholar] - Vaddirajua, S; Tomazos, I; Burgess, DJ; Jain, FC; Papadimitrakopoulos, F. Emerging synergy between nanotechnology and implantable biosensors: A review. Biosens. Bioelectron 2010, 25, 1553–1565. [Google Scholar] - Sadowski, M. The use of biological indicators in the development and qualification of moist heat sterilization processes. In Biological Indicators for Sterilization Processes; Gomez, M, Moldenhauer, J, Eds.; DHI Publishing: Bethesda, MD, USA, 2009; pp. 219–269. [Google Scholar] - George, LG; Vernon, MG; David, RS; Robert, KH; Charles, RP. Effect of moisture on ethylene oxide sterilization. Appl. Environ. Microbiol 1964, 12, 496–503. [Google Scholar] - Suzuki, H; Sugama, A; Kojima, N; Takei, F; Ikegami, K. A miniature Clark-type oxygen electrode using a polyelectrolyte and its application as a glucose sensor. Biosens. Bioelectron 1991, 6, 395–400. [Google Scholar] - Graham, GS; Mielnik, TJ. Industrial low-temperature gas plasma sterilization. Med. Device Technol 1997, 8, 28–30. [Google Scholar] - Yardimci, O; Setlow, P. Plasma sterilization: Opportunities and microbial assessment strategies in medical device manufacturing. IEEE Trans. Plasma Sci 2010, 38, 973–981. [Google Scholar] - Moussy, F; Harrison, DJ; O’Brien, DW; Rajotte, RV. In vitro and in vivo performance and lifetime of perfluorinated ionomer-coated glucose sensors after high-temperature curing. Anal. Chem 1994, 66, 3882–3888. [Google Scholar] - Herrmann, S; Oelsner, W; Kaden, H; Brischwein, M; Wolf, B. The influence of different methods of disinfection on the function of electrochemical sensors. Sens. Actuat. B 2000, 69, 164–170. [Google Scholar] - Iwaguch, S; Matsumura, K; Tokuoka, Y; Wakui, S; Kawashima, N. Sterilization system using microwave and UV light. Colloid. Surface. B 2002, 25, 299–304. [Google Scholar] - Abel, PU; von Woedtke, T. Biosensors for in vivo glucose measurement: Can we cross the experimental stage. Biosens. Bioelectron 2002, 17, 1059–1070. [Google Scholar] - Batzer, OF; Doty, DM. Radiation sterilization, nature of undesirable odors formed by gamma irradiation of beef. J. Agr. Food Chem 1955, 3, 64–67. [Google Scholar] - da Silva, EF; Nishioka, Y; Ma, TP. Radiation response of MOS capacitors containing fluorinated oxides. IEEE Trans. Nucl. Sci 1987, 34, 1190–1195. [Google Scholar] - Ma, TP; Dressenforder, PV. Ionizing Radiation Effects in MOS Devices and Circuits; John Wiley and Sons, Inc: New York, NY, USA, 1989. [Google Scholar] - Listvan, MA; Vold, PJ; Arch, DK. Ionizing radiation hardness of GaAs technologies. IEEE Trans. Nucl. Sci 1987, 34, 1663–1668. [Google Scholar] - Markus, H; John, H; Sharp, ID; Maren, F; Martin, S; Herwig, GP; Stefan, T. Real-time x-ray response of biocompatible solution gate AlGaN/GaN high electron mobility transistor devices. Appl. Phys. Lett 2010, 96, 092110. [Google Scholar] - Hsu, PY; Lin, JJ; Wu, YL; Hung, WC; Cullis, AG. Ultra-sensitive polysilicon wire glucose sensor using a 3-aminopropyltriethoxysilane and polydimethylsiloxane-treated hydrophobic fumed silica nanoparticle mixture as the sensing membrane. Sens. Actuat. B 2009, 142, 273–279. [Google Scholar] - Wu, YL; Hsu, PY; Lin, JJ. Polysilicon wire glucose sensor highly immune to interference. Biosens. Bioelectron 2011, 26, 2281–2286. [Google Scholar] - Lin, JJ; Hsu, PY; Wu, YL; Jhuang, JJ. Characteristics of polysilicon wire glucose sensors with a surface modified by silica nanoparticles/γ-APTES nanocomposite. Sensors 2011, 11, 2796–2808. [Google Scholar] - Berdichevsky, Y; Khandurina, J; Guttman, A; Lo, YJ. UV/ozone modification of poly(dimethylsiloxane) microfluidic channels. Sens. Actuat. B 2004, 97, 402–408. [Google Scholar] - Graubner, VM; Jordan, R; Nuyken, O. Photochemical Modification of Cross-Linked Poly(dimethylsiloxane) by Irradiation at 172 nm. Macromolecules 2004, 37, 5936–5943. [Google Scholar] - Wu, YL; Lin, JJ; Hsu, PY; Hsu, CP. Highly sensitive polysilicon wire sensor for DNA detection using silica nanopartiles/γ-APTES nanocomposite for surface modification. Sens. Actuat. B Chem 2011, 155, 709–715. [Google Scholar] - Lin, MC; Chu, CJ; Tsai, LC; Lin, HY; Wu, CS; Wu, YP; Wu, YN; Shieh, DB; Su, YW; Chen, CD. Control and detection of organosilane polarization on nanowire field-effect transistors. Nano Lett 2007, 7, 3656–3661. [Google Scholar] - Shalev, G; Haopern, E; Doron, A; Cohen, A; Rosenwaks, Y; Levy, I. Surface chemical modification induces nanometer scale electron confinement in field effect device. J. Chem. Phys 2009, 131, 024702. [Google Scholar] - Pena-Alonso, R; Rubio, J; Oteo, JL. Study of the hydrolysis and condensation of γ-Aminopropyltriethoxysilane by FT-IR spectroscopy. J. Mater. Sci 2007, 42, 595–603. [Google Scholar] - Pasternack, RM; Amy, SR; Chabal, YJ. Attachment of 3-(Aminopropyl)triethoxysilane on silicon oxide surfaces: dependence on solution temperature. Langmuir 2008, 24, 12963–12971. [Google Scholar] - Porti, M; Nafryía, M; Aymerich, X; Cester, A; Paccagnella, A; Cimino, S. Irradiation induced weak spots in SiO2 gate oxides of MOS devices observed with C-AFM. Electron. Lett 2005, 41, 101–103. [Google Scholar] - Porti, M; Nafryía, M; Aymerich, X; Cester, A; Paccagnella, A; Cimino, S. Leaky spots in irradiated SiO2 gate oxides observed with C-AFM. Proceedings of 2005 Spanish Conference on Electron Devices, Tarragona, Spain, 2–4 February 2005; pp. 53–56. © 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).

1. Twelve days ago A. Corporate Raider acquired 10 shares of stock in SMPL Corp. The Original Shareholders own the remaining 30 shares and the share price is currently $10. The Board of Directors of SMPL Corp. does not want Mr. Raider to gain control of the firm and, after consulting a recent graduate of a MBA program, have decided their best strategy is an exclusionary self tender offer to the Original Shareholders. If the Board uses cash to buy 10 shares from the Original shareholders at $15 per share, what will be the value of the 10 shares held by Mr. Raider after the tender offer is complete? In answering assume all original shareholders tender their shares and round to the nearest whole dollar. Answer: a. $150 b. $100 c. $83 d. $167 e. $63 2. A merger is more likely to succeed if: Answer: a. Management is able to correctly identify the specific sources of expected synergies. b. The acquiring firm uses an industry based discount rate to evaluate incremental cash flows from the merger. c. The target firm has no free cash flow. d. The bid price and the present value of synergy are evaluated using the flow-to-equity approach. e. The target firm has no preferred stock. 3. To increase the NPV of a merger management of the acquiring firm should: Answer: (a) Increase the premium paid for target shares. This is particularly effective for diversifying mergers and when acquirers use considerable amount of debt to fund the acquisition. This is known as the leverage effect and it works primarily by reducing the co-insurance discount. (b) Avoid paying a premium for target shares. (c) Reduce the estimate of synergies for the acquisition. One of the reasons so few mergers have a positive NPV is that management usually overestimates the value of synergies. (d) Use debt to finance the acquisition because the dollar volume of debt issues dominates equity issues by a considerable margin. (e)All of the above will increase the NPV of a merger. (f)None of the will increase the NPV of a merger. 4. If two leveraged firms merge, the cost of debt for the new firm will generally be lower than it was for the two firms as separate entities. One reason for this is Answer: (a) strategic fits. (b) net operating losses. (c) surplus funds. (d) co-insurance. (e) None of the above. Paper#5257 | Written in 18-Jul-2015Price : $25

Managing Institutional Complexity Regime Interplay and Global Environmental Change Publication Year: 2011 Published by: The MIT Press Title Page, Copyright During the preparation of the Science Plan for the long-term project on the Institutional Dimensions of Global Environmental Change (IDGEC) in 1997 and 1998, we spent a lot of time discussing what emerged as the project’s analytical themes, or the set of topics we deemed ripe for a major research push... This book is the youngest offspring of the Institutional Dimensions of Global Environmental Change (IDGEC) project. IDGEC was a core project of the International Human Dimensions Programme of Global Environmental Change (IHDP) from 1998 to 2007. It has since been succeeded by the... List of Abbreviations 1. Introduction: Institutional Interaction in Global Environment Change 2. Institutional Interaction: Ten Years of Scholarly Development Since the development of the Institutional Dimensions of Global Environmental Change (IDGEC) Science Plan in 1998 (Young et al. 1999/2005), institutional interaction has become an important subject of inquiry. The Science Plan served to put institutional interaction on the agenda of global change research... 3. Legal and Political Approaches in Interplay Management: Dealing with the Fragmentation of Global Climate Governance This chapter focuses on ways of dealing with the fragmentation of international regimes on climate change and the subsequent interactions among them. It assesses various means of interplay management with a view to enhancing synergy and mitigating conflict between regimes in this issue area... 4. Savings Clauses and the “Chilling Effect”: Regime Interplay as Constraints on International Governance The situations that environmental treaties address are necessarily linked to other policy fields, such as trade and human rights. Recent research suggests that environmental treaties are weakened by multilateral trade rules that address related issues (Conca 2000; Eckersley 2004; Stilwell and Tuerk... 5. Managing Policy Contradictions between the Montreal and Kyoto Protocols: The Case of Fluorinated Greenhouse Gases The international regimes for the protection of the ozone layer and for combating climate change have been at the forefront of global environmental governance since the mid-1980s. The ozone regime is based on the 1985 Vienna Convention for the Protection of the Ozone Layer and its 1987 Montreal Protocol... 6. Interplay Management, Niche Selection, and Arctic Environmental Governance This chapter develops and applies a framework for analyzing strategic interplay management decisions on specialization and division of labor within larger institutional complexes. The framework identifies several institutional niches, or governance tasks, that an institution may focus on within the broader... 7. The Role of Expert Networks in Reducing Regime Conflict: Contrasting Cases in the Management of Plant Genetic Resources A prominent example of institutional interplay is the disruption that has arisen among international institutions dealing with the conservation and use of genetic resources. Property rights to genetic resources are regulated by various international agreements that address the issue from different perspectives and with... 8. Regime Conflicts and Their Management in Global Environmental Governance Research on institutional interplay looks beyond the confines of a single institution, seeking to grasp its synergetic or disruptive interactions with other regimes or organizations. Despite the inherent centrality of institutional environments, however, most theoretical approaches stop short of considering the deeper... 9. The Institutional Complex of Trade and Environment: Toward an Interlocking Governance Structure and a Division of Labor This chapter examines the dynamics of the institutional complex of trade and the environment. The relationship between the world trade system and the numerous multilateral environmental agreements (MEAs) with trade restrictions is difficult. These institutions do not operate in isolation from each other... 10. UNCLOS, Property Rights, and Effective Fisheries Management: The Dynamics of Vertical Interplay The Third United Nations Convention on the Law of the Sea (UNCLOS III) yielded one of the most profound institutional changes to global environmental governance during the twentieth century. It converted a vast swath of oceanic space from a global commons to a regime characterized by 200-mile exclusive... 11. Interplay Management in the Climate, Energy, and Development Nexus The importance of integrating the three pillars of sustainable development — economic, social, and environmental — has been underscored in virtually every global policy process since the Brundtland Report was published in 1987. Even during the 1980s it was realized that environmental policies... 12. Conclusions: Decentralized Interplay Management in an Evolving Interinstitutional Order This book has focused on two themes central to institutional interaction: interplay management and institutional complexes. The contributions to this volume have addressed one or both of these issues by exploring various fields of international environmental governance, frequently investigating changes... List of Contributors Page Count: 376 Publication Year: 2011 OCLC Number: 759036874 MUSE Marc Record: Download for Managing Institutional Complexity

Real Green Living FEATURE ARTICLE - NOVEMBER/DECEMBER 2010 Community Investing Banks and the Economic Crisis Community investing banks don't promote the reckless practices that brought down the economy, and they use your dollars to provide much-needed services to underserved communities. With big changes occurring at two of the country’s largest and best-known community investing banks, socially responsible investors may be wondering how the current financial crisis is affecting community development financial institutions. Is the money in accounts at these banks safe? Is opening new accounts in these accounts a sound financial move? And what will happen to the social and environmental missions of the community investing banks where changes have taken place? Here’s what you need to know. Big Changes for a Community Investing Pioneer The Federal Deposit Insurance Corporation (FDIC) predicts that the number of banks that will fail this year will exceed 2009’s total of 140. Community investing banks are part of the broader banking world and are not immune to national economic developments and policies. Most are weathering the recession well, and their services to low-income communities are more essential than ever. However, ShoreBank, America’s first and best-known community development bank, has faced some difficulty in recent months. After 37 years of serving low-income areas of Chicago, ShoreBank’s Midwest bank became the 15th Illinois-based bank to shut its doors (albeit temporarily) since the beginning of the year. ShoreBank served some of the hardest hit areas in the country, including Detroit and Cleveland as well as the south side of Chicago. Unlike similar requests from many of its “too-big-to-fail” counterparts, ShoreBank’s request for Federal Troubled Asset Relief Program (TARP) funds was denied. “The US government failed to realize that by letting smaller banks fail, they are harming Main Streets across the country. Community investing banks lend to small, local businesses, which are the backbone of their community,” says Fran Teplitz, Green America’s director of social investing programs. ShoreBank Rises Again Fortunately, ShoreBank’s mission to lift up low- and moderate-income areas of Chicago, Cleveland, and Detroit will live on. This summer, Urban Partnership Bank, based in Chicago, stepped in and purchased ShoreBank’s assets. Urban Partnership Bank shares ShoreBank’s mission of providing loans and other financial services to underserved communities, so it will continue to advance ShoreBank’s work. If you are a customer of ShoreBank, don’t worry—your accounts will be transferred over to Urban Partnership Bank without an interruption in your services. No customers have lost any deposits, even those with over $250,000 in their accounts. ShoreBank assures its customers that “all banking business continues as usual, and all relationship managers remain the same.” The Urban Partnership Bank has also applied to become a certified community development financial institution (CDFI) through the US Treasury Department, further cementing its commitment to continue ShoreBank’s good work investing in communities that need it most. In addition, the new Urban Partnership Bank will be helmed by ShoreBank’s president and COO, William Farrow. The ShoreBank Pacific Merger Big changes are also afoot at ShoreBank Pacific, a Seattle-based subsidiary of ShoreBank and the bank with which Green America has a co-branded VISA card. ShoreBank Pacific plans to merge with OneCalifornia Bank, a CDFI focusing on lending to local businesses, nonprofits, and community organizations. The merger still needs to be approved by federal regulators, which is likely to take two to four months. The ShoreBank Pacific name will also likely change, though the new name has not yet been determined. The new entity will have assets of approximately $300 million and will serve low- and middle-income areas all along the US West Coast. “OneCalifornia Bank’s history of providing responsible, affordable financial services to low-wealth communities complements ShoreBank Pacific’s focus on financing environmentally sustainable businesses,” said Harry Haigood, chairman and CEO of OneCalifornia Bank. “We think this merger holds the promise of great synergy.” Your Deposits are Safe Don’t be afraid to put your money into a community development bank. Remember, all personal holdings in banks are insured up to $250,000 per financial institution by the FDIC, so you won’t lose any money up to that cap. That FDIC cap is effective until Dec. 31, 2013. Opening up accounts at multiple community development banks will help your money go to different projects and safeguard you in case a bank does fail and you are waiting to get your money back from the FDIC; your funds won’t all be tied up in one place. “Accounts in community investing banks are just as safe as those in mega-banks, and their mission is critical to fostering economic recovery in this financial crisis. They’re solving, rather than exacerbating the economic downturn,” reports Todd Larsen, Green America’s director of corporate responsibility programs. Your Deposits are Critical It is more important now than ever to invest in community development banks. CDFIs provide funding to communities where traditional financial institutions don’t usually dare to tread. Most large banks do not think it’s worth the time and paperwork to make loans for small businesses who will not be borrowing large amounts of money. Community investing banks often focus on small, local businesses as part of their mission. “People with accounts in community development banks are strengthening communities, in their own backyard and across the United States,” says Sylvia Panek of the Social Investment Forum. “These funds are playing a critical role today in America’s economic recovery, especially in areas hit hardest by the recent financial crisis, by drawing people back into the economic fabric of their community and promoting small business and job growth.” It was the mega-banks that were behind the creation of weak and predatory subprime mortgage products that helped create the economic crisis. In contrast, community development banks and credit unions help lift everyday people up and ensure a healthy, fair economy going forward. Given the choice between a federally insured mega-bank invested in weapons and coal-fired power plants, and a federally insured community development bank invested in day cares, organic farms, and sustainable forestry, it’s clear where your accounts can have the most powerful impact. For more information community investing, visit Green America’s CommunityInvest.org. What Is a Community Investing Bank? Community investing banks are a type of community development financial institution (CDFI), which work in areas that are underserved by traditional financial institutions. CDFIs are different from local “community banks” in that they have an express mission of funding community development initiatives. They grant loans for education, affordable housing, or business start-ups to deserving low- and moderate-income people whom traditional institutions might consider “unbankable,” and they provide financial training to help those loans succeed. In 1994, Congress created the CDFI Fund within the Department of the Treasury. The CDFI Fund certifies CDFIs and, since its inception, has provided upwards of $1 billion in federal funding to these institutions. There are 885 CDFIs across the US. For example, when Danny Schwartzman graduated from college, he wanted to open up a café in Minneapolis that served local, organic, and Fair Trade food and paid workers a living wage. He found few banks that were interesting in funding a start-up green restaurant with a young prospective owner—until he met with a representative from University Bank, a Sunrise Community Bank and a certified CDFI. After working with Schwartzman, University Bank not only financed the café, it gave him loans to turn the upper floors of the building he purchased into affordable-housing apartments. He also bought and renovated the building behind his. Since opening its doors in 2009, the Common Roots Café has become a bustling 120-seat restaurant that purchases organic ingredients from over 30 local producers. This “risky” business venture also created more than 30 jobs, helping to make downtown Minneapolis healthier and greener. More green-living articles from the Green American »

Check out Take Five Audio, they sell all 3, cryogenic treated. I've used the 2542 for ICs and speaker cable. I've used the 3104 biwire cable for power cords (star quad w/ reverse spirol ground). Cheap prices and good sound. With cryoed Neutrik RCAs($5.pr), and 2542, you've got pretty good cables for under $20.pr! TFA also sells Canare connectors, i'm not sure about their cable. I've also had good luck with Neotech 22g, single crystal copper w/ teflon, cryoed of course. Try building some, you'll get hooked! I used a Mogami XLR as an interconnect between preamp and amp for a short period. While it worked, it sounded more than a little thin and metallic to me. As soon as I replaced it with a Harmonic Technology Truthlink Silver, it was obvious that it was MUCH better than the Mogami. As always, your mileage may vary, but for my money, I think it's smarter to purchase used cables elsewhere. I like Zu for about the same price as the Mogami, or for a little more Harmonic, Tara Labs or Acoustic Zen. Mogami and canare are good wires. The usual marketing hype of the ""Audiophile"" cables will make any rational human crazy. Yeah some cables are worth a few extra bucks and do change the sound... but then you might just LIKE the sound of home-made Mogami etc. (This is for all the cable nuts that will pounce on this thread after I say Mogami is just as good...sigh.) I personally own some homemade interconnects with 1980 Mark Levinson wire, Some 1990 RadioShack 8mm pure copper wire, Some 2005 Belden teflon coax suggested by Jon Risch,... And a few Kimber AG and a few other $100 cables. I just cannot find a use for kilobuck cable BS. (Which is rather more in line with exotic stuff in any field, where the glamour is as important as the actual usability) And yeah, the kilobuck cables can sound better... But why bother? Spend the money on the basic equipment!!! Mogami will definitely get the job done. Oyaide PA-02 is more refined, and still doesn't cost much in the scheme of things. Just got some Mogami 3104 and Canare 4S11 to compare the two as speaker cables RIght off the bat - the Mogami copper is much deeper in color. Closer to a reddish copper while the Canare is more yellowish copper. The Canare does not claim to be OFC so this may be the reason for the color differences. Compared to the Canare 4S11 the Mogami has more conductors and each bundle of copper is composed of 7 bundles of smaller strands. Wednesday will be the night to listen to the Mogami and will report back. Running these two channel to biwire Aerial 10Ts Great for jump starting your car. I use 25', single ended mogami cables to feed the QVC amp for my bass horns. (I have a lot of pro gear in my system.) They have low capacitance which makes them great for longer runs. My Doshi preamp and phonostage are wired internally with Canare cable. Do a search on Mogami or Canare and see how many folks are using these products. Mogami 2534s for balanced xlr and 2549s for SE. Great for the price. Mogami 2534s for balanced xlr and 2549s for SE. Great for the price. Jazzgene (Threads | Answers | This Thread) My understanding is the 2534 has much more shielding than the 2549, so use it in areas of high RFI and the like. Otherwise, 2549 for balanced is fine, and is what I use. FWIW I bought a pair of 2549 XLR's for around $40. I ran them for a couple weeks but they sounded thin to me. I've had them in a box ever since, but recently took them out and put them back in the system. The current system is completely different than the one I had then. My immediate impression was one of neutrality over the other cables I was using, one being a pair of AZ Wow!! xlr's, the other a DIY braided silver design. Those cables both seem to sound a little bloated and glary in the mid-bass and bass. The Mogami's neither highlight nor obscure anything. Details in abundance, but also a natural tone. And again, neutral. Surprising to say the least. I've noticed as I've been playing them now for around 36 hours that the mids and bass are opening up as well. As with all things cables, and certainly in my case, system synergy is key. I think the Mogami's cleanness and apparent lack of midrange highlighting (coupled with surprising amounts of natural sounding detail) complement my system quite well. I didn't realize that the other cables, by comparison, were too much of a good thing -- warmer, but also thicker and with some midrange glare (I can't stand glare). The Mogami's lightness and nimbleness seem to be the ticket for me. The things I perceive as negatives with them are a slightly shrunken soundstage and a perceived bit of grain. Still, very enjoyable. Update after about 80 hours (+ previous break in from the last time I used them) -- I'm pretty impressed with the Mogami in my system. It is at the critical point between source (CDP) and preamp. First, I've never heard such precise imaging ever from my stereo. Vocals are reach-out-and-touch in front of me, as are other instruments/cues. Soundstaging also is very dimensional. Bass and mids have filled out nicely. And they have tamed some glary nasties I've been dealing with, one of the most appreciated improvements. All of the above equates to a much more musically involving experience. So for right now at least, they are staying put and I'm really enjoying them! I know of at least one high end company that marks the Mogami cables up by a factor of 10... How did you come to the conclusion that 2534 has more shielding than a 2549? They look the same braided shield to me. the 2534 is a quad and 2549, 2 conductor with shield. Anyway, to my ears, the 2534 sounded better than the 2549 in balanced configuration. The 2549 makes really great SE cables though. I use Mogami balanced between source (CDP) and amp. Bought 'em at Guitar Center, of all places. They had the 'Studio Gold' and I bought the 6' length. Good cable and I'd get 'em again over most others. How did you come to the conclusion that 2534 has more shielding than a 2549? I remember reading about this issue in various places on the web, though now I can't recall where exactly. Perhaps what I meant was that, as you stated, the 2534 is a quad cable while the 2549 is a twisted pair. The thing that stuck with me was that 2534 should be used in areas of high interference. If this situation doesn't exist, use the 2549. Anyway, here is a response I found on the Gearslutz forum by a Mogami rep to an inquiry about the differences between 2534 and 2549: "I do recommend 2534 anytime noise is the most important issue while being as transparent as possible. That is what we use in our Gold Studio cables. As I mentioned noise intrusion is often more noticeable when recording that last decibel above human hearing. If noise is not a big problem our 2549 is actually world class for a twisted pair noise rejection, and the golden ears among us can hear the difference in fidelity compared to the slightly softened transients of a quad. But we are definitely comparing subtleties here." There is more info on the Mogami website for these 2 cables. I have never heard 2534, either in balanced or SE, so can't comment on the differences from a personal experience. The 2534s sound much more transparant than the 2549s wired as SEs. The thing is I've never had interference problems with any cables... So I can't really say but in theory, the quad should be the best for noise. I just ordered a pair of 2534's from Redco. $45 shipped. Will compare to the 2549's and report any interesting findings. @Magfan, you found them at guitar center because they are marketed as a high end microphone cable for studio recording and live performance. At the price the quality of the cable is amazing. At higher prices the quality is still amazing, which is why so many recording studio's use Mogami to wire their systems. On the audiophile scene, this is actually the first time I've seen their cables brought up as a possible option. I use Mogami cables through-out my home recording studio (mostly with Neglex Quad wiring) with excellent results. I hadn't thought about them as an interconnect option outside the studio though. I split the two hobbies apart for some reason. glad to hear they are another great option!

Sample Logic has released Synergy, a Kontakt Player powered sample library featuring tempo-synced loops, and multis. Synergy utilizes extended sample synthesis and effectual techniques to provide you interactive, ready-to-play instruments. With Synergy’s flexible sound sculpting interface, control is in your hands. Simply put, all instruments can be modified, redesigned, and customized to your preference. This makes Synergy perfect for any performance and production environment. - 1200+ instruments, 18+ GB on 3 DVDs. - Sounds: Ambience (295 patches), Bass (54 patches), Drums (55 patches), Impacts (269 patches), Melody (173 patches), Pads (57 patches), Rhythms (270 patches), Multis (40 patches). - Jam-packed with: serene spiritual textures, deep rooted basses, Pop & Hip Hop flavored beats, haunting environments, lush emotional pads, mind-blowing explosions, multi-sampled ethnic and tribal instruments, gated angelic voices, electronic arpeggiated synths, bone-chilling sequenced impacts, melodic bells and whistles, adventurous flutes, action and world rhythms, funky leads, gigantic pianos, and mallets from the tropics, just to name a few… - Formats: VST, DXi, RTAS, AU, Standalone. Synergy is available now for $299 USD. Visit Sample Logic for more information and audio demos.

Shares of Spectranetics Corporation (NASDAQ:SPNC) went from $6.56 to as high as $7.20 before closing the day at up $.39 at $6.95 (+5.95%) after we told our premium readers on Wednesday that despite the fact company shares had been trading lower in previous days, the stock appeared undervalued. As we told our subscribers, Canaccord Adams analyst Jason Mills also thought the stock was a BUY with an $8.75 price target and on Thursday morning, the company announced that they had achieved record revenues of $32.2 million in the second quarter and 7% growth over the prior year. Other highlights from their key announcement included: - Lead Management revenue increased 15% compared with prior year second quarter - Vascular Intervention revenue continued turnaround with second consecutive quarter of sequential revenue growth, up 8% over first quarter 2011 levels - International revenue grew 42% over prior year second quarter - Net income of $584,000, or $0.02 per diluted share, a significant improvement compared with prior year second quarter net income of $91,000, or $0.00 per diluted share As we alerted, prior to today's news, Mills' thesis was that SPNC's proprietary LM business is worth the stock’s current valuation on its own, noting its growth profile (>10%), high barriers to entry, low penetration (<20%E), and SPNC’s leadership position with a proprietary, expanding product line. On the Vascular Intervention (VI) side, he realizes growth is currently sluggish, but he thinks VI has more value than is reflected currently in the stock, noting 1) new product launches upcoming; 2) first-mover ISR clinical trial starting soon; and 3) improving outpatient reimbursement environment, which augmented capital placements in Q1 – an important leading indicator. As such he has increased his year-end 2011 price target to $8.75 from $8.00, reflecting 1.9x our 2012 revenue estimate of $134M. The company recently gave an update on its progress regarding focus growth initiatives. We believe the most significant update comes in the form of the recently announced FDA approval to start the EXCITE in-stent restenosis trial. The company expects to begin enrollment within the next few weeks. The Spectranetics Corporation designs, manufactures, and markets single use medical devices used in minimally invasive surgical procedures within the cardiovascular system in conjunction with its proprietary excimer laser system, the CVX-300. The company’s lead management product line comprises excimer laser sheaths, non-laser sheaths, and cardiac lead management accessories for the removal of pacemaker and defibrillator cardiac leads. It sells its products in the United States, Canada, Europe, the Middle East, the Asia Pacific, Latin America, and Puerto Rico. The company has strategic alliances with Kensey Nash Corporation (KNSY) and ELANA BV. The Spectranetics Corporation was founded in 1984 and is based in Colorado Springs, Colorado. There are more forward looking news items to trade on. Even in these scared markets. We continue to expect positive near term positive catalysts for several other stocks, namely: Immunocellular Therapeutics (NYSEMKT:IMUC) -- On Thursday, Summer Street Research initiated coverage on the company with a Buy rating and price target of $8. While we feel the new price target may be a little high, there is definite upside at IMUC. This is particularly true if the firm announces an uplisting to the AMEX as previously reported. Once they are on a bigger exchange, the stock will get more attention from brokers, funds and institutionals. Their science platform is solid, their management team has shown that they can be very careful with cash management and they one of the leading candidates in the cancer immunotherapy space. A nice base has been building at the $2 mark and it should continue higher form here. Synergy Pharmaceuticals, Inc. (NASDAQ:SGYP), the developer of new drugs to treat gastrointestinal disorders and diseases also has a forward looking catalyst and some recent coverage from Joseph Morgan that calls for a $15 price target on the stock. Fellow Seeking Alpha contributor James Altucher has been following their story and reports the details in his latest write up. Finally, we continue to expect some positive news flow and developments from ChromaDex Inc. (NASDAQ:CDXC) despite the fact that the trading action has been extremely disappointing. At the close on Thursday, someone dumped shares immediately prior to the close and in doing so cut 10% out of the price- all on low volume. That action may have created a significant buying opportunity for traders because nothing has changed fundamentally. In fact, after speaking with management at the company, we know that full commercialization efforts at GNC Stores (NYSE:GNC) (and with others) are in full force and that the positive catalysts we reported recently are still on-tap. We are also hearing rumors that billionaire investor Phil Frost- and others who have a large position in the company- would love to see CDXC uplisted as well. The Amex- with a $2 price requirement- could be the most logical place where this one is headed. That tells you there continues to be a nice trade built-in here. Disclosure: I am long TPIV.OB.

A DREAM COME TRUE My, How Things Change… The manufactured housing industry is welcoming new life in a modern era. As design trends, building demands, and market influences converge, this industry is on the upswing as it evolves to meet today’s housing climate with transformed styles, options, and efficiencies. Today’s manufactured homes don’t carry the ‘assembly line’ style of eras gone by. Now these factory-built homes are being created to replicate the styles, architecture, and details found in traditional site-built homes. “The manufactured and modular housing industry is going through major evolutions, including the addition of more high-end homes to serve growing market demand. The industry has now started branching off into multi-family housing, such as townhouses constructed in factories and assembled onsite,” reports Chris Stinebert, President of the Manufactured Housing Institute (MHI), in Arlington, Virginia. Not surprisingly, imported hardwood plywood is increasingly used in the construction of manufactured homes. Imported plywood is often an unseen material in manufactured housing, selected for its high strength, light weight, and smoothness which allow the manufacturer to easily laminate paper or vinyl to meet any customer’s design need. Imports complement the work at hand for U.S. manufacturers of factory-built homes. The cost savings and versatility of these products are gateways to bringing in more diverse design elements and materials. “There is a huge movement within the industry to build homes that look like traditional residential homes, with features such as pitched roofs, gabled entries, dormers, large banks of windows, etc., that make the manufactured home compatible with almost any neighborhood style,” Stinebert explains. “Interiors feature open floor plans that adapt more readily to a family’s active lifestyle. There’s a greater concentration on providing all amenities you would find in a traditional site-built home, such as state-of-the-art kitchens, home entertainment centers, and luxurious baths in master suites. Pretty much what’s happening in housing is also happening in manufactured and modular homes.” This trend towards merging design styles of modular and traditional residential construction is expanding the use of imported woods throughout these manufactured homes. From underlayment in flooring or in solid components such as mouldings, imports are cost effective yet compromise no standards in terms of specifications. Lauan and meranti hardwood plywood are common elements of factory-built homes, as are softwood lumber and softwood panels, which are showing up more and more as designs advance. Today, more of these homes are also using wood in the exterior. In the past, vinyl siding or other types of siding typically viewed as less aesthetically appealing were commonly used. Approximately two of every ten new home starts in the U.S. are manufactured homes, and nearly 75 percent of those factory-built homes are multi-sectioned. These designs are providing more square footage, porches, vaulted ceilings, and other details once reserved for traditional site-built homes. Quality and design are continuously improving, making manufactured homes more structurally comparable to site-built construction. However, the affordability of manufactured homes is still superior because of the ability of U.S. manufacturers to use imported hardwood plywood and other imported wood products. These homes are many times first-homes to a demographic segment that would otherwise continue renting. In many areas of the country, exorbitant home prices and rising interest rates are beckoning even broader segments of the population to seek more affordable housing alternatives. Stinebert summarizes the connection between the imported wood industry and manufactured housing, “With more and more focus within the manufactured housing industry on providing amenities in our homes, there’s the natural synergy you would find with other forms of housing, such as counters, cabinets, entertainment centers, and so on. The industry has gone through the paradigm shift, and this opens the door to a lot more upscale amenities where this synergy comes to bear.” Copyright© 2006 by the International Wood Products Association. Published by Bedford Falls Communications, Inc. and circulated to an audience of 20,000 architects, designers, distributors, manufacturers, and users of imported wood products in North America. IWPA thanks our advertisers who provide the financial support of International Wood.

[Xerte] Linux, Mac OS X platforms samuel.rose at gmail.com Fri Mar 7 15:14:53 GMT 2008 Understood. As a participant in many open source projects, I can tell you that for every successful and vibrant OSS project, hundreds if not thousands die on the vine, for lack of community nourishment. Same thing with wiki communities, and other open knowledge resources, for that matter. This actually has nothing to do with the license that the software is released under, though. it has to do with people voting with their "feet" on what projects they want to volunteer time to. I know plenty of programmers (including myself) who release software that only they work on under GPL, yet still pull plenty of economic value from it. That is because the value extraction is shifting from control of IP to the point of consumption. One of my business partners wrote about this recently: Anyway, just wondered about the platform support, and wanted to register my 2 pence on a vote towards open license/transparent and reusable code. :) On Thu, Mar 6, 2008 at 10:42 AM, Tenney Julian < Julian.Tenney at nottingham.ac.uk> wrote: > No plans for Mac / Linux at the moment, I'm afraid. However, the file > format is open, and anyone can make their own editor for whatever platform > they like. > When I've done open source projects in the past, I have found it to be a > one way street. The promised legions of developers who would turn up and > freely give of their time to improve the code, fix all the bugs and write > the documentation never appeared. We have an open mind about open source - > we're not against it, but supporting an open source project would require a > significant investment of our time, which we don't have right now. > *From:* xerte-bounces at lists.nottingham.ac.uk [mailto: > xerte-bounces at lists.nottingham.ac.uk] *On Behalf Of *Samuel Rose > *Sent:* 06 March 2008 15:20 > *To:* xerte at lists.nottingham.ac.uk > *Subject:* [Xerte] Linux, Mac OS X platforms > Wondering if there are any active efforts to port this to Linux, Mac OS X? > Also, would like to cast a vote that this software code be released under > GPL copyright :) > Sam Rose > Social Synergy > Tel:+1(517) 639-1552 > Cel: +1-(517)-974-6451 > AIM: Str9960 > Linkedin Profile: https://www.linkedin.com/in/samrose > skype: samuelrose > email: samuel.rose at gmail.com > Related Sites/Blogs/Projects: > OpenBusinessModels: http://socialsynergyweb.net/cgi-bin/wiki/FrontPage > Information Filtering: > Xerte mailing list > Xerte at lists.nottingham.ac.uk Linkedin Profile: https://www.linkedin.com/in/samrose email: samuel.rose at gmail.com -------------- next part -------------- An HTML attachment was scrubbed... More information about the Xerte

Hi, I can chime in on your first question. I think the Salamander stand you have probably won't do a great job of supporting the Teres. That's my gut feeling from having worked with support for my evolving teres (form 135, to 245 to 255). I think you may encounter two issues. First is that the platform on top of the salamander simply isn't very high mass, and the Tere designs really seem to benefit from heavy, inert support. Second, having the Teres positioned high up on a rack exposes the table to microscopic horizontal swaying, which may impact tonearm tracking (that's a problem I encounter with my setup). If you do need to support the Teres is such a configuration, consider a wall mount that looks like the table is mounted on top of the stand, but is in fact a wall mount. It looks like a few owners have successfully done this with good results. Then, the height issue (horizontal vibrations) becomes a non issue, and you can apply a heavy mass support under the table. I would do that myself, only I'm renting the house I live in just now, so don't want to do too much DIY which will impact the walls. Finally, just wanted to mention, the 255 in person really looks great. I had a 245 and was thining I may miss the seamlessness of the acrylic spinning, and thought the lead in the 255 may look a big garish. However, the 255 really is a beauty, and seems to better balance a modern look (the platter) with a more traditional, refined look (the base). Still, I know that's all subjective ;-) Thanks Outlier - appreciate your comments. I really like the looks of the 255 as well, but need to do some selling at home (the lead/acrylic platter). I looked a long time to find a rack that had a door - so the stereo could be hidden. Maybe there is a high-mass, more stable rack available that has a door? While I don't own a Teres I am intimately familiar with them. You do need a high mass stand though but I wouldn't let what you are using stop the purchase. The wall mount would be okay especially if it were of welded construction. Regarding racks, there are numerous ones to copy online. I built a rack for Audiogon member Vetterone. Do a member search and take a look at it. Adding doors and sides would have been easy. I have strong opinions on the arms. Buy a Schroder. You'll never replace it unless you are going up Franks food chain. The entry level Schroder at $2200 with a carbon fiber arm wand is one of those "best buy in audio" pieces. You can mount a $10k cartridge on it and it will do the cartridge justice. In fact, we did that at a tonearm/cartridge shootout in Miami last month. I must admit the Triplanar is a stellar performer too. I'm sure you would be happy using the Blackbird with any of these arms. I'm also sure that if you can afford it you will later get a better cartridge and a different phono stage. The Teres/Schroder combination will tempt you too much to upgrade. I'll let others comment on the 265 vs. the 320. Vetterone has the 265 (plus Triplanar and ZYX Universe) and on the stand he uses it would be the end of the road for me. I've not listened to the 320. The 340 is bettered by the 360 enough that I would step up to the 360 if those were my choices. Hello Ecyclopediabsh, hi Patrick! Whichever Teres model you(or your shmbo) decides to purchase, any of them will only perform as well as the support allows it. First and foremost make it rigid and non-resonant. You might benefit from mass loading the base/rack, but this depends upon the floor the whole assembly is sitting on. A wall mounted rack is usually an excellent way to avoid the "swaying" phenomenon described by outlier, but if your wall is made of drywall you might open another can of worms(find at least one supporting beam). Then it is always possible to put an additional isolation device between the wall-mounted rack and the base of the table. One last thing to consider when going for a wall rack. You will be stuck with the location. If there is a room node right at that spot, then moving a conventional rack by a foot or so often cures the (feedback/bass)problem. Moving the wall-mounted rack, well... Buy/build the best support you can get, a 255/65 with a Moerch DP6 on a stable rack will outperform the same table with a Schröder No.2 on a shaky platform. I owned the 265 and now own the 320. While I believe that the TT is the most important part of the analog chain, in your case I would go with the 265 and the Schroder rather than the 320 and the Rega. I sold my 265 to a friend that has it on top of a wood cabinet similar to what you describe. If you lightly tap on it you can hear the problems with this type of setup but, it really isn't that big of a deal. You can work something out later. Meanwhile, just don't tap on it while your listening to music :). I can't comment on the Teres tables, but I can tell you that I have one of the Synergy S40 racks in my HT system. I would not site a TT on one of these, at least not long term. These racks move alot, I mean alot! Even with everything tightened down all. As Lugnut said, I wouldn't pass on the table because of this stand but you would want to do something more stable even for a suspended table. I own a Teres 265 sitting on a Salamander Triple 30. Both purchased for exactly the same reasons as you. Sometimes you gotta do what you gotta do. All the sentiments expressed above are true. The Salamander is a poor audio performer. As Agaffer said, if I tap anywhere on it while playing a record the thump is clearly audible. In fact, I can easily hear the hinges through the speakers when I open/close a door. So I don't thump on it and I leave the doors shut! Is this setup ideal? Hardly. The Salamander is unquestionably the weakest link in our system. Does it still make stupendous music. You bet. (Lugnut and Frank: to give you some perspective, despite the Salamander our system as a whole is tighter and *very* slightly more resolving than what we heard in Miami, and nearly as macro-dynamic. We just acquired the same power amp you heard there. It is a wonder.) Our Salamander also sits on a rather shaky suspended wood floor, which doesn't help of course. To isolate it somewhat from floor-borne vibrations there's a heavy-duty sorbathane hemisphere under each of the Salamander's eight feet. Certainly not what I'd like to have, but it does seem to help. FWIW, the TT does not audibly mistrack unless I literally jump up and down right next to it. Would I prefer a concrete floor and a solid, massive stand? Of course. I know I'd get stronger dynamics and a lower noise floor. Neither that nor a wall mount is an option, so we get by. Many of the advantages of the 320 vs. the 265 are independent of the support. Its greater mass provides a superior resonance sink. It has a better, quieter motor and a more massive and stable platter. While I certainly agree a better stand would be beneficial, I wouldn't let the Salamander influence the choice between these two particular TT's. OTOH... A 265/Morch DP6 will walk all over a 320/Expressimo Rega. I wouldn't put a modded Rega on any Teres except a 150 or maybe a 245. The 160, 255 and above all deserve a better arm. So if all-wood is mandatory I think a 265 + DP6 makes great sense. However, you should follow ASAP with a good pair of stepup trannies and a LOMC. HOMC's and MM's simply don't cut it at this level. A good LOMC and trannies will set you back another $3K or more, but a 265 and DP6 are certainly good enough to take advantage of them. If you can sell your spouse on the 255 then I'd go for that plus a DP6. This would leave more money available to put toward a better cartridge. When attempting use of a wall mount rack, be careful before drilling holes and positioning other associated equipment (regardless of table). As Schroder mentions, room nodes can be an issue - a serious issue. I built a wall rack using 1000lb rated Stanley brackets and a 3" rock maple base. I positioned where I THOUGHT I'd be okay and attached straight into wall the studs using SIX 3" lag bolts. The floor was a poured concrete slab. As one increased gain, the air borne resonances caused a terrible rumbling mess. Touching the wall near the supports - rock solid, not so much as a trace of vibration. Further out on the base - different story. Moral? The rack can be mounted like a pillar and while you can eliminate floor vibrations and all but eliminate wall vibrations, those air borne forces are much greater than one would think. A two foot repositioning solved the issue entirely, but the six holes required filling and repainting in the process. My two cents: All the posts above are logical. My suggestion would be for a Teres 265 or 320 and definitely a Schroder 2 or Reference. The Schroder arms are just incredible. Get a Reference and you are done for life. You need a stable platform for sure (home made might save money to allow for the better turntable and arm). I am in the process of actually setting up my Teres, at last. Finally got my HHG equipment stand on Friday so I could complete this set up. Because of space constraints I had to put all of my audio components on one stand instead of having the turntable on its own stand, as is recommended. So I have a 4 shelf stand plus the turntable on the top; the stand is made out of hardwoods and granite. All of this is on a wood floor, too. The stand itself actually weighs 350 lbs, but it is still not as massive as some people consider adequate. I am hoping for the best. It sure doesn't seem to have any sway or reaction to people moving around in the house, but I don't have my tonearm/cartridge set up as yet, so haven't tested everything with a record playing. Anyway, my situation isn't quite like yours other than not being ideal. I also have the Model 160 as opposed to the higher end models you are considering. But, though I have little experience with tonearms, so you can take this recommendation with a large grain of salt, I highly recommend the Morch DP6 tonearm. I heard it with a Model 255 and it was wonderful, and Chris was also highly pleased with the combo. I bought it from Chris the same day, with a 12" armwand. I will be using it with a ZYX R100H cartridge, their basic model (all I could afford) and it is also has great synergy with the Teres & the DP6. Good luck, Encyclopediabsh. Let us know what you decide to do and which Teres you decide to get. They are all things of beauty! Thanks to everyone for all the helpful suggestions. I really appreciate you taking the time to respond. I'll post a follow up after the final decision!

HOUSTON (KTRK) --A doctor whose office was raided by the DEA was in federal court Thursday, accused of running an illegal pain management clinic. Dr. Melanie Mencer-Parks is charged with one count of conspiracy to unlawfully distribute controlled substances. Court documents said she was illegally distributing drugs like hydrocodone and oxycodone at her office, Synergy Medical and Wellness Group, on the 1200 block of Binz Street. "I'm in shock because I had an appointment yesterday they canceled said she had an emergency and they scheduled me for today, so I'm in shock," said Shelby Mayo, one of Mencer-Parks' patients. SEE ALSO: Doctor arrested after DEA sting Mayo said while it is a shock, she's not surprised. She said she always got a bad vibe from her and some of her staff. "I initially stopped going to her because I didn't feel like she cared about my health," she said. Court documents reveal more information about Mencer-Parks' alleged operation: "...pain patients who planned to come to Synergy for a doctor's visit to obtain a prescription were required to call a specific number...the patients were given an appointment, which was scheduled on the office's appointment schedule, color coded to indicate a pain appointment. "After scheduling an appointment, the "patient" would come to Synergy at a specific time....upon arrival of pain patient..[they] would meet them outside the office to collect cash payment prior to the patient's appointment with Mencer-Parks." "I'm really not surprised," said Mayo. Prior to this arrest, Dr. Mencer-Parks was out on bond for another charge: In May of 2014, she was charged with conspiracy to commit healthcare fraud. Her trial was set for mid-September.

Work was carried out in a professional, flexible, friendly, and pleasant manner, while keeping within a tight timeframe. By combining my technical/system knowledge with the ability of Dr. Text staff to understand, help organize the concepts and express them in words was the perfect synergy. Dr. Text’s expertise is clear in the results: short and clear explanations, consistency in methods & structure, precision formatting, and other aspects. Your insistence on understanding the material, so that you could write it in such a way that the intended audience will understand, added to the excellent quality. I would like to thank all of you, and pass on the greetings. I hope we will continue our cooperation in the future. Dictionaries and Thesauri: Merriam-Webster Dictionary & Thesaurus Yahoo! Education Reference Encyclopedia, and more The Academy of the Hebrew Language Hebrew Terms Database Resources from the Plain English Campaign to write in plain English Punctuating bulleted lists A to Z of alternative words Ten tips for proofreading Guide to design and layout Basic grammar – parts of speech

Wikimedia@MW2010 is a workshop for exploring and developing policies that will enable museums to better contribute to and use Wikipedia or Wikimedia Commons, and for the Wikimedia community to benefit from the expertise in museums. It will bring together leaders in both communities to examine the opportunities for greater synergy between the museum sector and the Wikimedia community and the current barriers to collaboration. Specifically it will address rules, guidelines and examples that can be clarified to order to promote active engagement between the two communities. Attendance at Wikimedia@MW2010 will be by invitation. The Wikimedia Foundation has identified members of its Board, staff, and senior Wikipedia editors who will attend. Members of the museum community are invited to nominate themselves to attend before December 31, 2009 by providing the reasons they feel they will be able to contribute to the workshop, and to nominate up to three other members of the museum community who they think would be valuable to have in attendance (providing reasons for each). The Organizing Committee will review nominations (including self-nominations) and issue invitations in January 2010. Invited attendees will be asked to register for the workshop before the end of February. The topics to be addressed at the workshop will be determined from an open online discussion at http://conference.archimuse.com/forums/wikimediamw2010 Keywords: workshop, wikimedia, wikipedia, museums, poliicy, collaboration

Hello, I am a honest,sincere, responsible adult ,i pay my bills,my house is paid for in full,my cars are paid for. I am looking for someone who is also responsible. I am not flashy or try to impress anyone,I prefer content of character. I am very open minded and will be living abroad, six months out of the year. I have many interest from aviation to zoology ,I was a private pilot,haven't flown in years though, Being skilled with hands,feet,body,gymnastics, martial arts,hand to hand combat,don't like guns no skill needed , can use though police training years ago blah,favorite idols Bruce Lee,Nikola Tesla,martin Luther king,Albert Einstein, Bill Gates,JFK,RFK,Malcolm x,padre pio,Abe Lincoln,Bessie Coleman related:)Bill Gates,Michael Jordan,Stevie Wonder,Ray Charles. Eclecticism is my religion, very eclectic I am. Not interested if you are introverted, self absorbed ,superficial, bias or make assumptions based on anything other than actual interaction or experience. Rely solely on your looks as well, I am not the one,Best Wishes. Confidence and humble always good though:) I would love to meet one sincere lady who will take care of me as i will of her. Im not a serial dater so if you are please keep looking. Recently i've been more focused on career,future and health and it's been difficult here in California to find that synergy for a long term relationship. I've always had healthy relationships, but guess honestly I was afraid when it came easy back home in Chicago: ) so I'm paying for it here. Favorite songs Brian McKnight's fall 5.0 and just lemme know Stevie wonder as, minne loving you I'm here to find someone fun, energetic who loves adventures hiking, beach, concerts, simple dinners, just talking.Nothing smothering or serious to start, im not needy or the jealous type.Someone practical,who is willing to compromise, pays their bills, works together with their partner. Couldn't care less about type of car you drive, not impressed by cars. I'm impressed by stability, no drama,decisiveness, open mindedness, eclecticism,goals. Making best choice for you, not trying to impress anyone. I moved here from il and love to meet honest interesting people.I love music,all types, traveling, martial arts, cars, collecting movies, mechanically inclined computers, cars etc.I am looking for the character of your heart not the color of your skin. I like hearing different views, people with different backgrounds unique.I like quality dates which means I can have a great time with or without spending, because of our creativity a picnic n hiking or dinner and a play. I work fulltime have my own cars and place ,I can be hyper lol. Rather be alone than have kids for wrong reasons i.e. to trap someone ,doesn't matter how beautiful or successful you are. Which is why at 40 I've never fathered a child, I want a great friend and confidant.So I'm Open to to meet quality women as friends to just enrich our lives.Good quality people are getting harder to find, Or is it just me? It's so crazy I See so many attractive singles on sites.Is it because we see to much with our eyes and not with our hearts? Or are we so in tune with technology and less with human interaction? I'm not perfect, but strive to be more than I am , looking for the one who inspires me to climb higher, dive deeper and love stronger than ever before. Thank you to all the beautiful women who have read my profile, If I touched anyone I'm honored.MAY ALL FIND LOVE,PEACE AND A LIFE FULL OF JOY Moving to vegas bought a place got a dog:) A nice conversation over dinner, maybe a picnic or concerts been to a few jazz, brian mcknight, babyface etc just since I've been in cali want more, bike riding, museum.it all depends on the synergy between us. BTW first date picnic, music conversation at pier light wine, a walk along beach n watch the sunset

WELCOME TOYOUR REAL ESTATE WEBSITE This is the most useful real estate website in the area, with advanced search technologies that allow you to view listings in the MLS, or to ensure your own home is sold in reasonable time and for top dollar. You'll also find our web site to be a one-stop resource for your online real estate research. We're eager to tell you what we know about the local market for condos or homes, or preconstruction, or whatever is most interesting at the moment - that's where you'll usually find us! We delight in helping people succeed in this market, and when our clients come out of the transaction breathing that big sigh of relief, we're just as satisfied as they are. So please, have a look around, and contact us with any questions you might have about the market or our services. No question is too mundane - we want to help! About Middle Tennessee Real Estate The Middle Tennessee real estate market continues to be pretty stable. Currently, we’re seeing a seller’s market which is why you should list your house with an agent at Synergy today. Housing values are growing and there’s never been a better time to list. On the other hand, if you’re looking to buy in Nashville, we can help with that too. Our licensed, experienced agents can help you find the best home at the best deal in this market. Call us today at (615) 371 - 2424. In the heart of Tennessee is our state's rapidly growing capital, Nashville. Back in 1779 it was founded by James Robertson, John Donelson and American frontiersmen. It was given its name by Francis Nash, who was an American Revolutionary war hero. Once Nashville was founded, the city began to grow quickly, mostly because it was an important port on the Cumberland River. Following its creation, Nashville was named the state’s capital in 1843. The Battle of Nashville then took place two decades later, in 1864, and was an important Union victory. It didn’t take long after the Civil War for the city to get its shipping and trade positions back following the battle. Then, in the late 19th century the city really became prosperous. The 1970s were when Nashville’s growth was evident. That was followed in the 1990s by a huge economic boom. Phil Bredesen, who at the time was the Tennessee Mayor, helped improve the city’s landmarks by either building them or renovating them. Today we’re still seeing a lot of growth and Music City holds a special place in many people’s hearts. Nashville Voted No. 5 in the U.S. Travel + Leisure (link: http://www.travelandleisure.com/worlds-best/cities-in-us#intro) hosted their World’s Best Awards and Nashville got an impressive spot for 2016! The travel magazine asked readers to vote for the Best Cities in the U.S. and they voted Music City all the way to No. 5, scoring over an 85. According to the mag, they asked readers to vote based on “landmarks, culture, food, friendliness, shopping and overall value.” They concluded that these 15 cities all make visitors feel at home and that’s definitely something the Tennessee capitol prides itself on. Music City Sports Nashville is also home to an abundance of sports. The city has two professional sports teams — the Tennessee Titans and the Nashville Predators. The Titans now call Nissan Stadium home, a multi-purpose stadium which can fit over 69K people. It’s a gorgeous stadium with dual video boards so you never miss a minute of the action, no matter where your seats are. CMA Fest and concerts through the year are also housed in the stadium and, if you’re lucky, you can even catch a night of yoga on the field! The Nashville Predators call Bridgestone Arena home, which is also one of the most impressive concert venues in the city. Both sports teams continue to grow and improve every year, making Nashville proud. Nashville also has a minor league baseball team with a beautiful new stadium. We’re also home to the only guitar shaped scoreboard to watch the Nashville Sounds win! Vanderbilt, Lipscomb and Middle Tennessee are also an easy way to get your college sports fix in the Middle Tennessee area. Nashville’s Pleasant Weather Nashville’s weather is another factor that draws annual visitors. We have mild climates most of the time, although summer temperatures can get hot and humid. The winter doesn’t get too cold and snow, if any, is minimal. With this type of mild weather, it’s easy to enjoy the beautiful outdoors. As of 2013, Nashville’s city population was 659,042 and growing. Metro Nashville has 13 counties and, also as of 2013, the population of them was 1.7 million. That number made our city the largest metro city in the entire state of Tennessee. We are always looking for talented real estate agents to join our growing team! Click HERE to Discover Synergy! The data relating to real estate for sale on this web site comes in part from the Internet Data Exchange Program of RealTracs Solutions. Real estate listings held by brokerage firms other than Synergy Realty Network are marked with the Internet Data Exchange Program logo or thumbnail logo and detailed information about them includes the name of the listing brokers. Disclaimer: All information is believed to be accurate but not guaranteed and should be independently verified. All properties are subject to prior sale, change or withdrawal. Copyright 2016 RealTracs Solutions. Listing information last updated on October 26th, 2016 at 1:35pm CDT.

Head and neck squamous cell carcinoma (HNSCC) patients are at an increased risk of developing a second primary tumor (SPT) or recurrence following curative treatment. 13-cis-retinoic acid (13-cRA) has been tested in chemoprevention clinical trials but the results have been inconclusive. We genotyped 9,465 SNPs in 450 patients from the Retinoid Head and Neck Second Primary Trial. SNPs were analyzed for associations with SPT/recurrence in patients receiving placebo to identify prognosis markers and further analyzed for effects of 13-cRA in patients with these prognostic loci. Thirteen loci identified a majority subgroup of patients at a high risk of SPT/recurrence and in whom 13-cRA was protective. Patients carrying the common genotype of rs3118570 in the retinoid X receptor (RXRA) were at a 3.33-fold increased risk (95% confidence interval [CI], 1.67–6.67) and represented over 70% of the study population. This locus also identified individuals who received benefit from chemoprevention with a 38% reduced risk (95% CI, 0.43–0.90). Analyses of cumulative effect and potential gene-gene interactions also implicated CDC25C:rs6596428 and JAK2:rs1887427 as two other genetic loci with major roles in prognosis and 13-cRA response. Patients with all three common genotypes had a 76% reduction in SPT/recurrence (95% CI, 0.093–0.64) following 13-cRA chemoprevention. Carriers of these common genotypes constituted a substantial percentage of the study population, indicating that a pharmacogenetics approach could help select patients for 13-cRA chemoprevention. The lack of any alternatives for reducing risk in these patients highlights the need for future clinical trials to prospectively validate our findings. HNSCC; SPT; single nucleotide polymorphisms; retinoids Agents can enter clinical development for cancer prevention either initially or after previous development for a different indication, such as arthritis, with both approaches consuming many years of development before an agent is fully evaluated for cancer prevention. We propose the following, third approach: Reverse migration, that is, importing agents, targets and study designs to personalize interventions, and concepts developed in advanced cancer to the setting of cancer prevention. Importing these “ready-made” features from therapy will allow reverse migration to streamline preventive-agent development. We recently reported the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial of personalized lung-cancer therapy and now propose the reverse-migration development of personalized lung-cancer prevention based on the BATTLE model. chemoprevention; personalized; targeted; lung cancer Dysplastic lesions of the oral epithelium are known precursors of oral cancer. A significant proportion of oral dysplastic lesions have functional defects in p53 response pathways. The ONYX-015 adenovirus is selectively cytotoxic to cells carrying defects in p53-dependent signaling pathways. The current study sought to establish the feasibility and activity of ONYX-015 administered topically as a mouthwash to patients with clinically apparent and histologically dysplastic lesions of the oral mucosa. Patients and Methods A total of 22 patients (19 assessable patients) were enrolled onto the study. ONYX-015 was administered on three different schedules to consecutive cohorts. Biopsies of the involved mucosa were performed to evaluate histologic response and changes in expression of putative markers of malignant potential, including p53, cyclin D1, and Ki-67. Serology was performed to measure antiadenoviral titers. Histologic resolution of dysplasia was seen in seven (37%) of 19 patients, and the grade of dysplasia improved in one additional patient. The majority of responses were transient. No toxicity greater than grade 2 (febrile episode in one patient) was observed. Only one of seven patients demonstrated an increase in circulating antiadenoviral antibody titer while on therapy. Although responding and resistant lesions had similar mean p53 staining at baseline, histologic response correlated with a decrease in p53 positivity over time. Significant changes in cyclin D1 or Ki-67 were not observed. Viral replication was confirmed in two of three lesions examined. This novel approach to cancer prevention is tolerable, feasible, and has demonstrable activity. PDGF/PDGFR pathway has been implicated in malignant pleural mesothelioma (MPM) carcinogenesis and evidence suggests autocrine mechanisms of proliferation. We sought to evaluate the incidence of PDGFRB gene copy number gain (CNG) by fluorescence in situ hybridization (FISH) and PDGFR pathway protein expression by immunohistochemistry (IHC) and correlate it to patient clinical outcome. 88 archived tumor blocks from resected MPM with full clinical information were used to perform IHC biomarkers (PDGFRα, PDGFRβ, p-PDGFRβ) and FISH analysis of PDGFRB gene CNG. Spearman's rank correlation, Wilcoxon rank-sum test, Kruskal-Wallis test, BLiP plots, and Kaplan-Meier method were used to analyze the biomarkers and correlation to clinical outcome. Several correlations between the IHC biomarkers were seen; however, none correlated to clinically relevant patient demographics or histology. In the CNG analysis, PDGFRB gene CNG in > 10% of tumor cells had lower cytoplasmic p-PDGFRβ (p=0.029), while PDGFRB gene CNG in > 40% of tumor cells had a higher cytoplasmic PDGFRβ (p=0.04). PDGFRB gene CNG status did not associate with patient demographics or tumor characteristics. PDGFR pathway IHC biomarkers did not associate with survival outcomes. However, patients with PDGFRB CNG > 40% of tumor cells had improved relapse-free survival [HR 0.25 (95% CI 0.09, 0.72), p=0.0096] and improved overall survival [HR 0.32 (95% CI 0.11, 0.89), p=0.029]. PDGFRB CNG > 40% of MPM tumor cells is a potential prognostic biomarker for surgery and may identify a unique population of mesothelioma patients. Future validation of this biomarker in prospective trials is needed. PDGFRB; pleural mesothelioma; copy number gain; prognostic biomarker Lung adenocarcinoma, the most common subtype of lung cancer, is the leading cause of cancer death worldwide. Despite attempts for the treatment of lung cancer which have been accumulating, promising new therapies are still needed. Here, we found that cyclic-AMP response element-binding protein (CREB)-CREB binding protein (CBP) transcription factors complex inhibitor, Naphthol AS-TR phosphate (NASTRp), is a potential therapeutic agent for lung cancer. We show that NASTRp inhibited oncogenic cell properties through cell cycle arrest with concomitant suppression of tumor-promoting autophagy with down-regulations of Atg5-12 and Atg7, and accumulation of p62 in human lung cancer cell lines. In addition, NASTRp induced expression of endoplasmic reticulum stress markers such as DDIT3/CHOP, and led to apoptosis along with Bim induction. These findings suggest that transcription factor/co-activator complex, CREB-CBP, can be a potential therapeutic target and its inhibition could be a novel therapeutic strategy for lung cancer. Earlier work identified specific tumor-promoting abnormalities that are shared between lung cancers and adjacent normal bronchial epithelia. We sought to characterize the yet unknown global molecular and adjacent airway field cancerization (FC) in early-stage non–small cell lung cancer (NSCLC). Whole-transcriptome expression profiling of resected early-stage (I–IIIA) NSCLC specimens (n = 20) with matched tumors, multiple cytologically controlled normal airways with varying distances from tumors, and uninvolved normal lung tissues (n = 194 samples) was performed using the Affymetrix Human Gene 1.0 ST platform. Mixed-effects models were used to identify differentially expressed genes among groups. Ordinal regression analysis was performed to characterize site-dependent airway expression profiles. All statistical tests were two-sided, except where noted. We identified differentially expressed gene features (n = 1661) between NSCLCs and airways compared with normal lung tissues, a subset of which (n = 299), after gene set enrichment analysis, statistically significantly (P < .001) distinguished large airways in lung cancer patients from airways in cancer-free smokers. In addition, we identified genes (n = 422) statistically significantly and progressively differentially expressed in airways by distance from tumors that were found to be congruently modulated between NSCLCs and normal lung tissues. Furthermore, LAPTM4B, with statistically significantly increased expression (P < .05) in airways with shorter distance from tumors, was upregulated in human immortalized cells compared with normal bronchial epithelial cells (P < .001) and promoted anchorage-dependent and -independent lung cancer cell growth. The adjacent airway FC comprises both site-independent profiles as well as gradient and localized airway expression patterns. Profiling of the airway FC may provide new insights into NSCLC oncogenesis and molecular tools for detection of the disease. Background: EphA5 is a functional target in lung cancer, the most common cause of tumor-related death in mankind. Results: EphA5 regulates cell cycle checkpoints and DNA damage repair induced by ionizing radiation. Conclusion: EphA5 is a novel regulator of DNA damage repair with clinical implications. Significance: EphA5 may serve as a novel biomarker of radioresistance and a candidate target for therapeutic intervention in human lung cancer. Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. Cell Cycle; DNA Damage; DNA Damage Response; DNA Repair; Monoclonal Antibody; Receptor Tyrosine Kinase; Ionizing Radiation In a previous trial, we found that combined 13-cis retinoic acid (13-cRA), interferon-α and α-tocopherol more effectively reversed advanced premalignant lesions of the larynx than of the oral cavity and that cyclin D1 (CD1)G/A870 single nucleotide polymorphism correlated with cancer risk. We conducted the present trial primarily to confirm the clinical activity of the combination in advanced laryngeal premalignancy and to confirm and extend our findings on CD1, both genotype and protein expression, in association with cancer risk in this setting. Twenty-seven moderate-to-severe laryngeal dysplasia patients underwent induction with combined 13-cRA daily, α-interferon twice weekly, and α-tocopherol daily for one year; 14 non-progressing patients then were randomized to maintenance fenretinide or placebo for two years. During induction, 2 patients had pathological complete responses, 6 had partial responses (30% overall response rate), and 5 developed laryngeal cancer. There were no significant differences between maintenance fenretinide and placebo in response or cancer rates. Ten patients developed cancer overall. Twenty-four patients were evaluated for the CD1 G/A870 genotype, and 23 for pre- and post-treatment CD1 protein expression. Consistent with our earlier report, shorter cancer-free survival was associated with the CD1 AA/AG genotype (p = 0.05). Extending our earlier work, high CD1 expression was associated with worse cancer-free survival overall (p= 0.04) and within each CD1 genotype group. These findings support CD1 genotype and protein expression as important risk markers for laryngeal cancer and suggest future trials targeting upstream regulators of CD1 transcription. Premalignant lesions; larynx; biochemoprevention; cyclin D1 genotype; cyclin D1 protein expression Investigate the mechanisms of regulation and role associated with EZH2 expression in lung cancer cells. We investigated the mechanisms of EZH2 expression associated with the vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR-2) pathway. Furthermore, we sought to determine the role of EZH2 in response of lung adenocarcinoma to platinum-based chemotherapy, as well as the effect of EZH2 depletion on VEGFR-2–targeted therapy in lung adenocarcinoma cell lines. Additionally, we characterized EZH2 expression in lung adenocarcinoma specimens and correlated it with patients’ clinical characteristics. In this study, we demonstrate that VEGF/VEGFR-2 activation induces expression of EZH2 through the upregulation of E2F3 and HIF-1α, and downregulated expression of miR-101. EZH2 depletion by treatment with 3-deazaneplanocin A and knockdown by siRNA decreased the expression of EZH2 and H3K27me3, increased PARP-C level, reduced cell proliferation and migration, and increased sensitivity of the cells to treatment with cisplatin and carboplatin. Additionally, high EZH2 expression was associated with poor overall survival in patients who received platinum-based adjuvant therapy, but not in patients who did not receive this therapy. Furthermore, we demonstrated for the first time that the inhibition of EZH2 greatly increased the sensitivity of lung adenocarcinoma cells to the anti-VEGFR-2 drug AZD2171. Our results suggest that VEGF/VEGFR-2 pathway plays a role in regulation of EZH2 expression via E2F3, HIF-1α and miR-101. EZH2 depletion decreases the malignant potential of lung adenocarcinoma and sensitivity of the cells to both platinum-based and VEGFR-2–targeted therapy. EZH2; NSCLC; VEGF/VEGFR-2 pathway; DZNep Both the lungs and oral cavity are exposed to tobacco carcinogens in smokers. We hypothesized that the oral epithelium undergoes molecular alterations similar to those in lungs and therefore may be used as a surrogate tissue to assess tobacco-induced molecular alterations. Promoter methylation of p16 and FHIT genes was analyzed with methylation-specific PCR in 1,774 oral and bronchial brush specimens (baseline and 3 months after intervention) from 127 smokers enrolled in a prospective randomized placebo-controlled chemoprevention trial. The association between methylation patterns in oral tissues and bronchial methylation indices (methylated sites/total sites per subject) was analyzed blindly. At baseline, promoter methylation was observed in 23%, 17%, and 35% of the bronchial tissues for p16, FHIT, and either of the two genes, respectively, which were comparable to the 19%, 15%, and 31% observed in the oral tissues. Among the 125 individuals with available data from both oral and bronchial tissues, strong correlations were observed between tissues from the two sites (P<0.0001 for both p16 and FHIT). Among the 39 individuals with oral tissue methylation in either of the two genes, the mean bronchial methylation index was 0.53 (± 0.29) compared with only 0.27 (± 0.26) for the 86 subjects without oral tissue methylation (P<0.0001). Similar correlations were also observed in samples obtained at 3 months after chemopreventive intervention. The oral epithelium may be used as a surrogate tissue to assess tobacco-induced molecular damage in lungs, which has an important implication in conducting biomarker-based lung cancer prevention trials. Cigarette smoke is the major cause of lung cancer and can interact in complex ways with drugs for lung cancer prevention or therapy. Molecular genetic research promises to elucidate the biologic mechanisms underlying divergent drug effects in smokers versus non-smokers and to help in developing new approaches for controlling lung cancer. The present study compared global gene expression profiles (determined via Affymetrix microarray measurements in bronchial epithelial cells) between chronic smokers, former smokers, and never smokers. Smoking effects on global gene expression were determined from a combined analysis of three independent datasets. Differential expression between current and never smokers occurred in 591 of the 13,902 genes measured on the microarrays (P < 0.01 and >2 fold change; pooled data)—a profound effect. In contrast, differential expression between current and former smokers occurred in only 145 of the measured genes (P < 0.01 and >2 fold change; pooled data). Nine of these 145 genes showed consistent and significant changes in each of the three datasets (P < 0.01 and >2 fold change), with 8 being down-regulated in former smokers. Seven of the 8 down-regulated genes, including CYP1B1 and 3 AKR genes, influence the metabolism of carcinogens and/or therapeutic/chemopreventive agents. Our data comparing former and current smokers allowed us to pinpoint the genes involved in smoking–drug interactions in lung cancer prevention and therapy. These findings have important implications for developing new targeted and dosing approaches for prevention and therapy in the lung and other sites, highlighting the importance of monitoring smoking status in patients receiving oncologic drug interventions. To identify the genetic factors that influence overall survival in never smokers who have non-small cell lung cancer (NSCLC), we performed a consistency meta-analysis study utilizing genome-wide association approaches for overall survival in 327 never smoker NSCLC patients from the MD Anderson Cancer Center and 293 cases from the Mayo Clinic. We then performed a two-pronged validation of the top 25 variants that included additional validation in 1,256 NSCLC patients from Taiwan and assessment of expression quantitative trait loci (eQTL) and differential expression of genes surrounding the top loci in 70 tumors and matched normal tissues. A total of 94 loci were significant for overall survival in both MD Anderson and Mayo studies in the consistency meta-analysis phase, with the top 25 variants reaching a p-value of 10−6. Two variants of these 25 were also significant in the Taiwanese population: rs6901416 (HR:1.44, 95%CI:1.01-2.06) and rs10766739 (HR:1.23, 95%CI:1.00-1.51). These loci resulted in a reduction in median survival time of at least 8 and 5 months in three populations, respectively. An additional six variants (rs4237904, rs7976914, rs4970833, rs954785, rs485411, and rs10906104) were validated through eQTL analysis that identified significant correlations with expression levels of six genes (LEMD3, TMBIM, ATXN7L2, SHE, ITIH2, and NUDT5, respectively) in normal lung tissue. These genes were also significantly differentially expressed between the tumor and normal lung. These findings identify several novel, candidate prognostic markers for NSCLC in never smokers, with eQTL analysis suggesting a potential biological mechanism for a subset of these observed associations. CXCR2 in non-small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53-mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC. Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in 52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was determined in 70 human NSCLC cell lines. Invasion and metastasis were decreased in CXCR2 knockdown clones in vitro and in vivo. SB225002 decreased invasion in vitro. In lung adenocarcinomas, CXCR2 expression in tumor cells was associated with smoking and poor prognosis. CXCR2 axis gene expression profiles in human NSCLC cell lines and lung adenocarcinomas defined a cluster driven by CXCL5 and associated with smoking, poor prognosis and RAS pathway activation. Expression of CXCL5 was regulated by promoter methylation. The CXCR2 axis may be an important target in smoking-related lung adenocarcinoma. lung cancer; prognosis; metastasis; CXCR2; chemokine Gene expression alterations in response to cigarette smoke have been characterized in normal-appearing bronchial epithelium of healthy smokers and it has been suggested that adjacent histologically normal tissue display tumor-associated molecular abnormalities. We sought to delineate the spatial and temporal molecular lung field of injury in smoker early stage non-small cell lung cancer (NSCLC) patients (n=19) who were accrued into a surveillance clinical trial for annual follow-up and bronchoscopies within one year after definitive surgery. Bronchial brushings and biopsies were obtained from six different sites in the lung at the time of inclusion in the study and at 12, 24 and 36 months after the first time point. Affymetrix Human Gene 1.0 ST arrays were used for whole-transcript expression profiling of airways (n=391). Microarray analysis identified gene features (n=1165) that were non-uniform by site and differentially expressed between airways adjacent to tumors relative to more distant samples as well as those (n=1395) that were significantly altered with time up to three years. In addition, gene-interaction networks mediated by PI3K and ERK1/2 were modulated in adjacent compared to contralateral airways and the latter network with time. Furthermore, phosphorylated AKT and ERK1/2 immunohistochemical expression were significantly increased with time (nuclear pAKT, p=0.03; cytoplasmic pAKT, p<0.0001; pERK1/2, p=0.02) and elevated in adjacent compared to more distant airways (nuclear pAKT, p=0.04; pERK1/2, p=0.03). This study highlights spatial and temporal cancer-associated expression alterations in the molecular field of injury of early stage NSCLC patients after definitive surgery that warrant further validation in independent studies. Early stage NSCLC; gene expression profiling; lung airway epithelium; chemoprevention Most patients with non–small cell lung cancer (NSCLC) have responded poorly to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We investigated the involvement of insulin-like growth factor 1 receptor (IGF-1R) signaling in primary resistance to EGFR TKIs and the molecular determinants of resistance to IGF-1R TKIs. Phosphorylated IGF-1R/insulin receptor (pIGF-1R/IR) was immunohistochemically evaluated in a NSCLC tissue microarray. We analyzed the antitumor effects of an IGF-1R TKI (PQIP or OSI-906), either alone or in combination with a small-molecular inhibitor (PD98059 or U0126) or with siRNA targeting K-Ras or MAPK/extracellular signal-regulated kinase kinase (MEK), in vitro and in vivo in NSCLC cells with variable histologic features and EGFR or K-Ras mutations. pIGF-1R/IR expression in NSCLC specimens was associated with a history of tobacco smoking, squamous cell carcinoma histology, mutant (mut) K-Ras, and wild-type (wt) EGFR, all of which have been strongly associated with poor response to EGFR TKIs. IGF-1R TKIs exhibited significant antitumor activity in NSCLC cells with wt EGFR and wt K-Ras but not in those with mutations in these genes. Introduction of mut K-Ras attenuated the effects of IGF-1R TKIs on NSCLC cells expressing wt K-Ras. Conversely, inactivation of MEK restored sensitivity to IGF-TKIs in cells carrying mut K-Ras. The mutation status of both EGFR and K-Ras could be predictive markers of response to IGF-1R TKIs. Also, MEK antagonism can abrogate primary resistance of NSCLC cells to IGF-1R TKIs. EGFR; K-Ras; IGF-1R; lung cancer; TKI The development of second primary tumors (SPT) or recurrence alters prognosis for curatively-treated head and neck squamous cell carcinoma (HNSCC) patients. 13-cis-retnoic acid (13-cRA) has been tested as a chemoprevention agent in clinical trials with mixed results. Therefore, we investigated if genetic variants in the PI3K/PTEN/AKT/MTOR pathway could serve as biomarkers to identify which patients are at high risk of an SPT/recurrence while also predicting response to 13-cRA chemoprevention. A total of 137 pathway SNPs were genotyped in 440 patients from the Retinoid Head and Neck Second Primary Trial and assessed for SPT/recurrence risk and response to 13-cRA. Risk models were created based on epidemiology, clinical, and genetic data. Twenty-two genetic loci were associated with increased SPT/recurrence risk with six also being associated with a significant benefit following chemoprevention. Combined analysis of these high-risk/high-benefit loci identified a significant (P = 1.54×10−4) dose-response relationship for SPT/recurrence risk, with patients carrying 4–5 high-risk genotypes having a 3.76-fold (95%CI:1.87–7.57) increase in risk in the placebo group (n=215). Patients carrying 4–5 high-risk loci showed the most benefit from 13-cRA chemoprevention with a 73% reduction in SPT/recurrence (95%CI:0.13–0.58) compared to those with the same number of high-risk genotypes who were randomized to receive placebo. Incorporation of these loci into a risk model significantly improved the discriminatory ability over models with epidemiology, clinical, and previously identified genetic variables. These results demonstrate that loci within this important pathway could identify individuals with a high-risk/high-benefit profile and are a step towards personalized chemoprevention for HNSCC patients. TAS-106, a RNA polymerase inhibitor, was studied in solid tumors with potential clinical benefit and reasonable tolerability. We conducted a multicenter, international phase II trial of TAS-106 in salvage metastatic or recurrent head and neck squamous cell cancer (HNSCC) and nasopharyngeal cancer (NPC) patients. TAS-106 monotherapy was given at 6.5 mg/m2 over 24-h continuous infusion every 3 weeks. Translational studies for blood and tissue were included. Twenty-seven enrolled patients experienced the most common drug-related adverse events of neutropenia, fatigue, non-neutropenic fever, injection site reaction, and skin rash/dermatitis. The greater than or equal to grade 3 adverse events included neutropenia (14.8%), febrile neutropenia (7.4%), pneumonia (7.4%), and peripheral neuropathy (3.7%). The overall response rate was 0% in both subgroups; five HNSCC patients had stable disease (median duration 99 days) and four NPC patients had stable disease (median duration of 92.5 days). Median progression-free survival (PFS) for HNSCC patients was 52 days (95% CI 43.0–99.0 days) and 48 days (95% CI 41.0–83.0 days) for NPC. Median overall survival (OS) for HNSCC patients was 175 days (95% CI 92.0–234.0 days) and 280 days (95% CI 107.0–462.0 days) for NPC. The TAS-106 plasma levels were equivalent between Asian and Caucasian patients. There was no significant correlation of tumor UCK2 protein expression levels to TAS-106 efficacy. TAS-106 was reasonably tolerated in patients with platinum-failure HNSCC and NPC. The administration schedule of 24-h continuous infusion prevented neurologic toxicity, but had myelosuppression as its main toxicity. There was no anti-tumor efficacy seen with TAS-106 monotherapy. Future studies will focus on TAS-106 combinations and mechanisms of drug resistance. Head and neck squamous cell carcinoma; nasopharyngeal cancer; TAS-106 The purpose of this study was to characterize insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) expression in patients with non-small cell lung cancer (NSCLC). A total of 459 patients who underwent curative resection of NSCLC were studied (median follow-up duration, 4.01 years). Expression of the IR and IGF-1R protein in tumor specimens was assessed immunohistochemically using tissue microarrays. The cytoplasmic IR score was higher in patients with adenocarcinoma (ADC) than in those with squamous cell carcinoma (SCC) whereas cytoplasmic IGF-1R score was higher in patients with SCC than those with ADC. Neither IR nor IGF-1R expression was associated with sex, smoking history, or clinical stage. Patients with positive IR or IGF-1R expression levels had poor recurrence-free (RFS) (3.8 vs. 3.3 years; 3.8 vs. 2.0 years, respectively), but similar overall survival (OS). Patients with high expression levels of IR and IGF-1R had shorter RFS and OS compared to those with low levels of IR and/or IGF-1R expression. Finally, a multivariate analysis revealed the impact of IR, but not of IGF-1R, as an independent predictive marker of NSCLC survival: hazard ratio (HR) for OS, 1.005 (95% confidence interval [CI], 1.001 – 1.010], HR for RFS, 1.005 (95% CI, 1.001 – 1.009), when IR score was tested as a continuous variable. Overexpression of IR predicts a poor survival among patients with NSCLC, especially those with SCC. These results might serve as future guidance to the clinical trials involving IR or IGR-1R targeting agents. Carcinoma; Non-Small-Cell Lung; Receptor; Insulin; Receptor; IGF Type 1; Prognosis; Survival Tumor cell proliferation requires both growth signals and sufficient cellular bioenergetics.The AMP-activated kinase (AMPK) pathway appears dominant over the oncogenic signaling pathway suppressing cell proliferation. This study investigated the preclinical efficacy of targeting the tumor bioenergetic pathway using a glycolysis inhibitor 2-deoxy glucose (2DG) and AMPK agonists, AICAR and metformin. We evaluated the in vitro anti-tumor activity of 2DG, metformin or AICAR alone, and 2DG in combination either with metformin or AICAR. We examined in vivo efficacy using xenograft mouse models. 2DG alone was not sufficient to promote tumor cell death, reflecting the limited efficacy demonstrated in clinical trials. A combined use of 2DG and AICAR also failed to induce cell death. However, 2DG and metformin led to significant cell death associated with decrease in cellular ATP, prolonged activation of AMPK, and sustained autophagy. Gene expression analysis and functional assays revealed that the selective AMPK agonist AICAR augments mitochondrial energy transduction (OXPHOS) while metformin compromises OXPHOS. Importantly, forced energy restoration with methylpyruvate reversed the cell death induced by 2DG and metformin, suggesting a critical role of energetic deprivation in the underlying mechanism of cell death. The combination of 2DG and metformin inhibited tumor growth in mouse xenograft models. Deprivation of tumor bioenergetics by dual inhibition of energy pathways might be an effective novel therapeutic approach for a broad spectrum of human tumors. Tumor bioenergetics; Targeted therapy; Cancer energy metabolic pathway Lung cancer is the leading cause of cancer death, developing over prolonged periods through genetic and epigenetic changes induced and exacerbated by tobacco exposure. Many epigenetic changes including DNA methylation and histone methylation and acetylation are reversible, and agents that can modulate these aberrations are a potentially effective approach to cancer chemoprevention. Combined epigenetic-targeting agents have gained interest for their potential to increase efficacy and lower toxicity. The present study applied recently developed statistical methods to validate the combined effects of the demethylating agent 5-aza-2-deoxycytidine (5-AZA-CdR, or AZA, or decitabine) and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, or vorinostat). This validation compared AZA alone with SAHA alone and with their combinations (at later or earlier time points and in varying doses) for inhibiting the growth of cell lines of an in vitro lung carcinogenesis system. This system comprises isogenic premalignant and malignant cells that are immortalized (earlier premalignant), transformed (later premalignant), and tumorigenic human bronchial epithelial (HBE) cells (immortalized BEAS-2B and its derivatives 1799 [immortalized], 1198 [transformed], and 1170-I [tumorigenic]). AZA alone and SAHA alone produced a limited (< 50%) inhibition of cell growth, whereas combined AZA and SAHA inhibited cell growth more than did either agent alone, reaching 90% inhibition under some conditions. Results of drug-interaction analyses in the Emax model and semiparametric model supported the conclusion that the drug combinations exert synergistic effects, i.e., beyond additivity in the Loewe model. The present results demonstrate the applicability of our novel statistical methodology for quantitatively assessing drug synergy across a wide range of doses of agents with complex dose-response profiles, a methodology with great potential for advancing the development of chemopreventive combinations. lung cancer; epigenetics; vorinostat; decitabine; premalignant; epithelial cells Retinoids have shown antiproliferative and chemopreventive activity. We analyzed data from a randomized, placebo-controlled chemoprevention trial to determine whether a 3-month treatment with either 9-cis-retinoic acid (RA) or 13-cis-RA and α-tocopherol reduced Ki-67, a proliferation biomarker, in the bronchial epithelium. Former smokers (n = 225) were randomly assigned to receive 3 months of daily oral 9-cis-RA (100 mg), 13-cis-RA (1 mg/kg) and α-tocopherol (1200 IU), or placebo. Bronchoscopic biopsy specimens obtained before and after treatment were immunohistochemically assessed for changes in the Ki-67 proliferative index (i.e., percentage of cells with Ki-67–positive nuclear staining) in the basal and parabasal layers of the bronchial epithelium. Per-subject and per–biopsy site analyses were conducted. Multicovariable analyses, including a mixed-effects model and a generalized estimating equations model, were used to investigate the treatment effect (Ki-67 labeling index and percentage of bronchial epithelial biopsy sites with a Ki-67 index ≥ 5%) with adjustment for multiple covariates, such as smoking history and metaplasia. Coefficient estimates and 95% confidence intervals (CIs) were obtained from the models. All statistical tests were two-sided. In per-subject analyses, Ki-67 labeling in the basal layer was not changed by any treatment; the percentage of subjects with a high Ki-67 labeling in the parabasal layer dropped statistically significantly after treatment with 13-cis-RA and α-tocopherol treatment (P = .04) compared with placebo, but the drop was not statistically significant after 9-cis-RA treatment (P = .17). A similar effect was observed in the parabasal layer in a per-site analysis; the percentage of sites with high Ki-67 labeling dropped statistically significantly after 9-cis-RA treatment (coefficient estimate = −0.72, 95% CI = −1.24 to −0.20; P = .007) compared with placebo, and after 13-cis-RA and α-tocopherol treatment (coefficient estimate = −0.66, 95% CI = −1.15 to −0.17; P = .008). In per-subject analyses, treatment with 13-cis-RA and α-tocopherol, compared with placebo, was statistically significantly associated with reduced bronchial epithelial cell proliferation; treatment with 9-cis-RA was not. In per-site analyses, statistically significant associations were obtained with both treatments. Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection or prevention strategies are urgently needed to increase survival. Hyperplasia is the first morphologic change that occurs in the bronchial epithelium during lung cancer development, followed by squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor. The current study was designed to determine the molecular mechanisms that control bronchial epithelium hyperplasia. Using primary normal human tracheobronchial epithelial (NHTBE) cells cultured using the 3-dimensional organotypic method, we found that the epidermal growth factor receptor (EGFR) ligands EGF, transforming growth factor-alpha, and amphiregulin induced hyperplasia, as determined by cell proliferation and multilayered epithelium formation. We also found that EGF induced increased cyclin D1 expression, which plays a critical role in bronchial hyperplasia; this overexpression was mediated by activating the mitogen-activated protein kinase pathway but not the phosphoinositide 3-kinase/Akt signaling pathway. Erlotinib, an EGFR tyrosine kinase inhibitor, and U0126, a MEK inhibitor, completely inhibited EGF-induced hyperplasia. Furthermore, a promoter analysis revealed that the activator protein-1 transcription factor regulates EGF-induced cyclin D1 overexpression. Activator protein-1 depletion using siRNA targeting its c-Jun component completely abrogated EGF-induced cyclin D1 expression. In conclusion, we demonstrated that bronchial hyperplasia can be modeled in vitro using primary NHTBE cells maintained in a 3-dimensional (3-D) organotypic culture. EGFR and MEK inhibitors completely blocked EGF-induced bronchial hyperplasia, suggesting that they have a chemopreventive role. NHBE; bronchial hyperplasia; dysplasia; erlotinib; MEK inhibitor To compare the characteristics of HER receptors and their ligands deregulation between primary tumor and corresponding brain metastases of non-small cell lung carcinoma (NSCLC). Fifty five NSCLC primary tumors (PT) and corresponding brain metastases (BM) specimens were examined for the immunohistochemical expression of EGFR, phosphorylated (p)–EGFR, Her2, Her3, and p-Her3, and their ligands EGF, TGF-α, amphiregulin, epiregulin, betacellulin, heparin-binding EGFR-like growth factor, and neuregulins-1 and -2. Analysis of EGFR copy number using fluorescent in situ hybridization and mutation by PCR-based sequencing was also performed. Metastases showed significantly higher immunohistochemical expression of EGF (membrane, BM 66.0 vs. PT 48.5; P=0.027; and nucleus, BM 92.2 vs. 67.4; P=0.008), amphiregulin (nucleus, BM 53.7 vs. PT 33.7; P=0.019), p-EGFR (membrane, BM 161.5 vs. PT 76.0; P<0.0001; and cytoplasm, BM 101.5 vs. PT 55.9; P=0.014), and p-Her3 (membrane, BM 25.0 vs. PT 3.7; P=0.001) than primary tumors (PT) did. Primary tumors showed significantly higher expression of cytoplasmic TGF–α (PT 149.8 vs. BM 111.3; P=0.008) and neuregulin-1 (PT 158.5 vs. BM 122.8; P=0.006). In adenocarcinomas, a similar high frequency of EGFR copy number gain (high polysomy and amplification) was detected in primary (65%) and brain metastasis (63%) sites. However, adenocarcinoma metastases (30%) showed higher frequency of EGFR amplification than corresponding primary tumors (10%). Patients whose primary tumors showed EGFR amplification tended to develop brain metastases at an earlier time points. Our findings suggest that NSCLC brain metastases have some significant differences in HER family receptors-related abnormalities from primary lung tumors. Interindividual variation in genetic background may influence the response to chemotherapy and overall survival for patients with advanced-stage non–small cell lung cancer (NSCLC). To identify genetic variants associated with poor overall survival in these patients, we conducted a genome-wide scan of 307 260 single-nucleotide polymorphisms (SNPs) in 327 advanced-stage NSCLC patients who received platinum-based chemotherapy with or without radiation at the University of Texas MD Anderson Cancer Center (the discovery population). A fast-track replication was performed for 315 patients from the Mayo Clinic followed by a second validation at the University of Pittsburgh in 420 patients enrolled in the Spanish Lung Cancer Group PLATAX clinical trial. A pooled analysis combining the Mayo Clinic and PLATAX populations or all three populations was also used to validate the results. We assessed the association of each SNP with overall survival by multivariable Cox proportional hazard regression analysis. All statistical tests were two-sided. SNP rs1878022 in the chemokine-like receptor 1 (CMKLR1) was statistically significantly associated with poor overall survival in the MD Anderson discovery population (hazard ratio [HR] of death = 1.59, 95% confidence interval [CI] = 1.32 to 1.92, P = 1.42 × 10−6), in the PLATAX clinical trial (HR of death = 1.23, 95% CI = 1.00 to 1.51, P = .05), in the pooled Mayo Clinic and PLATAX validation (HR of death = 1.22, 95% CI = 1.06 to 1.40, P = .005), and in pooled analysis of all three populations (HR of death = 1.33, 95% CI = 1.19 to 1.48, P = 5.13 × 10−7). Carrying a variant genotype of rs10937823 was associated with decreased overall survival (HR of death = 1.82, 95% CI = 1.42 to 2.33, P = 1.73 × 10−6) in the pooled MD Anderson and Mayo Clinic populations but not in the PLATAX trial patient population (HR of death = 0.96, 95% CI = 0.69 to 1.35). These results have the potential to contribute to the future development of personalized chemotherapy treatments for individual NSCLC patients. Emerging evidence suggests that aberrant expression of oncogenes contributes to development of lung malignancy. The thyroid transcription factor 1 (TITF-1) gene functions as a lineage survival gene abnormally expressed in a significant fraction of NSCLCs, in particular lung adenocarcinomas. To better characterize TITF-1 abnormality: patterns in NSCLC, we studied TITF-1’s gene copy number using fluorescent in situ hybridization (FISH) and quantitative PCR, as well as its protein expression by immunohistochemistry analysis in a tissue microarray comprised of surgically resected NSCLC (N=321) including 204 adenocarcinomas and 117 squamous cell carcinomas (SCCs). TITF-1 copy number and protein expression were correlated with patients’ clinicopathologic characteristics, and in a subset of adenocarcinomas with EGFR and KRAS mutation status. We found that increased TITF-1 protein expression was prevalent in lung adenocarcinomas only and was significantly associated with female gender (p<0.001), never smokers (p=0.004), presence of EGFR mutations (p=0.05) and better overall survival (all stages, p=0.0478. stages I and II, p=0.002). TITF-1 copy number gain (CBG) was detected by FISH analysis in both adenocarcinomas (18.9%; high CNG, 8.3%) and SCCs (20.1%; high CNG, 3.0%), and correlated significantly with the protein product (p=0.004) and presence of KRAS mutations (p=0.008) in lung adenocarcinomas. Moreover, multivariate analysis revealed that TITF-1 copy number gain was an independent predictor of poor survival of NSCLC (p=0.039). Our integrative study demonstrates that the protein versus genomic expression patterns of TITF-1 have opposing roles in lung cancer prognosis and may occur preferentially in different subsets of NSCLC patients with distinct oncogene mutations. NSCLC; TITF-1; gene copy gain; lineage-specific oncogenes

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Volume 19, Number 7—July 2013 Verona Integron–encoded Metallo-β-Lactamase 1 in Enterobacteria, Ontario, Canada To the Editor: Among Enterobacteriaceae, Verona integron–encoded metallo-β-lactamase 1 (VIM-1) has been found only in Klebsiella pneumoniae in North America (1). We report 4 VIM-1–producing Enterobacteriaceae isolated from 4 patients at 3 hospitals in Ontario, Canada. Patient 1, a 61-year-old man, was initially hospitalized in Italy for presumed pneumonia and was treated with levofloxacin during his 6-month stay in Italy. Upon returning to Ontario, Canada, he was admitted to hospital 1 in August 2010 because of diabetic ketoacidosis and began empiric treatment with metronidazole and gentamicin. Urine cultures were positive for a carbapenem-resistant Escherichia coli (strain GN531). Two days later, the patient had a fever and a blood culture was positive for E. coli (strain GN532), which was also resistant to carbapenems. During his hospitalization, the patient was isolated and received droplet precaution because of his travel history until he was discharged home. Patient 2, a 76-year-old man, was admitted to hospital 2 in May 2011 because of a recurrent urinary tract infection (urine was positive for E. coli). The patient was given ciprofloxacin. On day 49, a carbapenem-sensitive Enterobacter cloacae was isolated from urine. On day 61, a carbapenem-resistant E. cloacae was isolated from urine culture (strain GN719). Contact precautions were used until the patient was discharged to a long-term care facility on day 80. Patient 3, an 81-year-old man, was admitted to hospital 2 (November 2011) 2 months after patient 2 was discharged. Urine culture at admission was positive for a carbapenem-resistant E. cloacae (strain GN825). The patient was given ceftriaxone and metronidazole and then given ertapenem. The patient died on day 110. Patients 2 and 3 had no hospital room in common during their admissions and both received contact precautions for methicillin-resistant Staphylococcus aureus before isolation of the carbapenem-resistant isolates. Patient 4, a 90-year-old woman, was admitted to hospital 3 in November 2011 because of nausea, vomiting, and diarrhea. In the preceding 6-month period, she had recurrent Clostridium difficile–associated diarrhea and a urinary tract infection. At admission, a carbapenem-susceptible Proteus spp. was isolated from a urine culture. The patient was given a 3-day course of ciprofloxacin and vancomycin. On day 17, a carbapenem-resistant E. cloacae was isolated from urine (strain GN738). Because this organism was also isolated from a rectal swab specimen, it was assumed that the urine sample might be contaminated by her feces. Therefore, the patient did not receive additional treatment other than that for recurrent C. difficile–associated diarrhea. Patients 2, 3, and 4 had no history of travel outside Canada. All 5 isolates were submitted for reference purposes to the Public Health Ontario Laboratories. Pulsed-field gel electrophoresis showed that E. coli GN531 and GN532 were indistinguishable (GN531 was selected for further studies), and the 3 E. cloacae isolates had similar fingerprint patterns. All strains displayed synergy in presence of meropenem disks plus dipicolinic acid, which is indicative of metallo-β-lactamase inhibition (2). The 4 clinical strains displayed a multidrug resistance phenotype, and were susceptible only to tigecycline and colistin (Table). PCR and sequencing identified blaVIM-1 in all isolates (Table). Multilocus sequence typing classified E. coli GN531 as sequence type (ST) 131 (6), the epidemic strain that spreads blaCTX-M-15 worldwide (7). E. coli ST131 with similar phenotypic and genetic features was described in Florence, Italy, in 2009 (8). Because E. coli GN531 was isolated from patient 1, who had received heath care in Italy before being hospitalized in Ontario, this patient might have been exposed to this strain in Italy. A similar scenario was reported in the first case of VIM-1–producing K. pneumoniae in the United States, which was isolated from a patient who received health care in Greece (1). The presence of a metallo-β-lactamase in E. coli ST131 is of great concern because it increases the potential for dissemination of drug-resistance genes. An IncN plasmid (5) harboring blaVIM-1 was transferred from GN531 to E. coli by conjugation (Table). The blaCTX-M-15 gene was not co-transferred, which indicated that it was located on another plasmid or the chromosome of the clinical isolate. After several attempts, no transconjugants derived from E. cloacae were obtained. E. coli TOP10 (Life Technologies, Carlsbad, CA, USA) was transformed with VIM-1 plasmids obtained from E. cloacae GN719 and GN825 (T-719 and T-825, respectively). E. coli transformation with plasmid extracts from E. cloacae GN738 was unsuccessful. Pulsed-field gel electrophoresis with S1 nuclease (9) and Southern blot analysis identified VIM-1-containing plasmids; estimated sizes were 65 kb (E. coli GN531), 50 kb (E. cloacae GN738), and 30 kb (E. cloacae GN719 and GN825). In conclusion, VIM-1 was found among Enterobacteriaceae from 3 geographically distant nosocomial units in Ontario, Canada. Although E. cloacae strains were clonally related, there were no clear epidemiologic links between these patients, suggesting that the clone or resistance gene maybe circulating in the province on a greater scale than believed. Emergence of E. coli ST131, a pandemic multidrug-resistant clone that causes predominantly community-onset infections (7), and produces simultaneously CTX-M-15 and VIM-1, could be a serious threat for the dissemination of these drug-resistance elements. We thank Prasad Rawte, Stephen Lo, and Heather Siebert for providing technical support. - Centers for Disease Control and Prevention. Update: detection of a Verona integron-encoded metallo-β-lactamase in Klebsiella pneumoniae—United States, 2010. MMWR Morb Mortal Wkly Rep. 2010;59:1212 . - Giske CG, Gezelius L, Samuelsen Ø, Warner M, Sundsfjord A, Woodford N. A sensitive and specific phenotypic assay for detection of metallo-β-lactamases and KPC in Klebsiella pneumoniae with the use of meropenem disks supplemented with aminophenylboronic acid, dipicolinic acid and cloxacillin. Clin Microbiol Infect. 2011;17:552–6 . - Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 20th Informational supplement M100–S20. Wayne (PA): The Institute; 2010. - Tijet N, Alexander DC, Richardson D, Lastovetska O, Low DE, Patel SN, New Delhi metallo-β-lactamase, Ontario, Canada. Emerg Infect Dis. 2011;17:306–7 . - Carattoli A, Bertini A, Villa L, Falbo V, Hopkins KL, Threlfall EJ. Identification of plasmids by PCR-based replicon typing. J Microbiol Methods. 2005;63:219–28. - Wirth T, Falush D, Lan R, Colles F, Mensa P, Wieler LH, Sex and virulence in Escherichia coli: an evolutionary perspective. Mol Microbiol. 2006;60:1136–51. - Rogers BA, Sidjabat HE, Paterson DL. Escherichia coli O25b-ST131: a pandemic, multiresistant, community-associated strain. J Antimicrob Chemother. 2011;66:1–14. - Mantengoli E, Luzzaro F, Pecile P, Cecconi D, Cavallo A, Attala L, Escherichia coli ST131 producing extended-spectrum β-lactamases plus VIM-1 carbapenemase: further narrowing of treatment options. Clin Infect Dis. 2011;52:690–1. - Barton BM, Harding GP, Zuccarelli AJ. A general method for detecting and sizing large plasmids. Anal Biochem. 1995;226:235–40. - Table. VIM-1–producing Escherichia coli and Enterobacter cloacae clinical isolates, derivative transconjugants, and transformants, Ontario, Canada Suggested citation for this article: Tijet N, Macmullin G, Lastovetska O, Vermeiren C, Wenzel P, Stacey-Works T, et al. Verona integron–encoded metallo-β-lactamase 1 in Enterobacteria, Ontario, Canada [letter]. Emerg Infect Dis [Internet]. 2013 Jul [date cited]. http://dx.doi.org/10.3201/eid1907.121294 Please use the form below to submit correspondence to the authors or contact them at the following address: Roberto G. Melano, Ontario Agency for Health Protection and Promotion, Public Health Laboratory Branch, 81 Resources Rd, Toronto, Ontario M9P 3T1, Canada Comment submitted successfully, thank you for your feedback. The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above. - Page created: May 24, 2013 - Page last updated: May 24, 2013 - Page last reviewed: May 24, 2013 - Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Office of the Director (OD)

Mayfair, United Kingdom (PressExposure) March 02, 2009 -- Elemis, the pioneering British spa and skin care brand, has unveiled its new Tri-Enzyme Resurfacing Gel Mask, which is due for release in April 2009. Elemis has recognised the problem of the skin's cell renewal process declining as people age. In 2006, after three years of research, Elemis launched a skin care programme that facilitated natural cell renewal of the dead skin cells to reveal a fresher, more radiant skin. This range was the Tri-Enzyme Programme which won several beauty awards after its launch including being voted the CEW Best New Skincare range 2007. Following on from this success is Elemis' latest innovation; the new Tri-Enzyme Resurfacing Gel Mask. This new product is a highly active gel based mask that combines the Elemis-patented Tri-Enzyme Technology with anti ageing Tetra Peptide, Amazonian Acerola Cherry, White Truffle, Great Burdock, Erysiumum and amino acids to encourage effective resurfacing of the skin's surface. Elemis Tri-Enzyme Technology adapts to the individual's micro flora and skin condition, an important factor given that everyone's skin is different. When the skin's acid mantle drops below 4.5pH, enzymatic action decreases dramatically, resulting in rapid ageing. Elemis Tri-Enzyme Technology uses the synergy of Organic Acids with micro-encapsulated enzymes to support the micro flora enabling safe and highly effective skin resurfacing. Noella Gabriel, Elemis' Director of Product and Treatment Development, said: "After years of research we wanted to bring clients a resurfacing gel mask that is an active system to 'take home'. Sadly, in the last few years, we have constantly been confronted with customers suffering with damaged skin from too harsh and abrasive treatments which have left their skin unsafely thin on the surface, very sensitive and in need of TLC. At Elemis we are proud to be able to offer a safe, yet powerful resurfacing programme that works naturally with the skin's natural resources. It is our promise that we only create products that adapt to the individual's skin as everyone's skin is different. This Gel Mask gives skin a remarkable, visible radiance." The Try-Enzyme Programme includes a resurfacing homecare regime designed to address concerns including fine lines and wrinkles, acne and superficial scarring and uneven pigmentation.

Google Buzz new feature seeks to integrate all other communication methods, mainly through Gmail, into a social networking model. This could render sites like Facebook and MySpace obsolete, but only in that it could allow people to monitor a variety of feeds from one single hub. This centralization is of incredible interest to iPhone and other smart phone users as the mobile device is increasingly becoming a force on integration with other technological and communicative modes. Google has already begun bringing many of their services to the iPhone, and almost every other online communication service ranging from instant message to full social networking sites have been brought into normal iPhone functioning. Google Buzz is, essentially, as social networking tool. It allows you to use a variety of media types, just as in other social networking sites, to communicate in a more back and forth format. None of this is new to users of sites like YouTube, Twitter, or Flickr, but that is not what is stated to be revolutionary about Google Buzz. Instead it is the integration that has been a central aspect of Google's business model. All of these features are being added into Gmail so that you can have a single location for all networking communication. Along with this is the integration of other sites like Twitter, Blogger, Picasa, Google Reader, YouTube, and others. Because of this integration it presents itself as a more complete opponent to Facebook, which is now the social networking standard. What Google Buzz really means for the base Google company is synergy. Since you can now integrate all your email contacts with your phone contacts through Google there seems to be no reason to not do the same with your social networking friends as well. Sites like Facebook have been trying to combat this by making their iPhone applications tie into the phone call functions easily, but if people already have large contact lists inside their email account this may act as an atom bomb. The other question around this is if it is really enticing enough to warrant people completely shifting services all together. The features of Google Buzz are not surprising, but this is also the first eruption of a social networking service after mobile platforms have become a standard place for social networking. This means that to truly integrate into the culture Google has to make Google Buzz available in a unique format that will make it easy to use from your iPhone or other smart phone. Google has made big waves about how it was going to integrate the features of the iPhone into this, but this has mainly been about the use of Maps and GPS features. This will help with the locator once you first log into Google Buzz. To get Google Buzz on your iPhone you can go through a relatively simple process set up through the Google website. Go to http://www.google.com/mobile/buzz/ and find at the right hand side of the web page there will be a Sent to Phone button. This will allow you to send a text message with the buzz.google.com link to your iPhone. Just enter in your phone number and hit send, which will almost instantly appear as a text message on your iPhone. Select the link and this will take you to Google in the Buzz tab. It will ask to use your general location, which it will then select a news feed for you out of Google Buzz users in your area. This is going to be adjacent to your own selected feeds, which really just works as Twitter does. The directions to activate Google Buzz from your iPhone are not difficult, but you may be wondering why you would have to go through Safari for a service like this. FaceBook, MySpace, YouTube, and a variety of Twitter applications have already made their way onto the iPhone. Every one of these services is made accessible on the iPhone through a curtailed application because even the most iPhone friendly web service is difficult through Safari. Seeing as media is going to be a central part of using Google Buzz it is unclear how Google attempts to remedy the lack of video support and slow photo load times that come through Safari. If Google really wants the Buzz to resonate with smart phone users it will have to develop a comparable application that did what Google Earth did and make it simple and easy to use right from the touch screen. It is likely that Google Buzz will develop even further and add more and more features as months turn into years, but it is going to be no good if mobile devices are not kept front and center of this.

Key Specifications Table |Species Reactivity||Key Applications||Host||Format||Antibody Type| |H, M||IP, WB||Rb||Purified||Polyclonal Antibody| |Presentation||Protein A Purified immunoglobulin in 0.1M Tris-glycine, pH 7.4, 0.15M NaCl, and 0.05% sodium azide.| |Application||Anti-LAT Antibody detects level of LAT & has been published & validated for use in IP & WB.| |Safety Information according to GHS| |Storage and Shipping Information| |Storage Conditions||Stable for 1 year at 2-8°C from date of receipt. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.| |Material Size||400 µg| |Anti-LAT (rabbit polyclonal IgG) - 2189948||2189948| |Anti-LAT (rabbit polyclonal IgG) - 2227257||2227257| |Anti-LAT (rabbit polyclonal IgG) - 2243497||2243497| |Anti-LAT (rabbit polyclonal IgG) - 2322513||2322513| |Anti-LAT - 16842||16842| |Anti-LAT - 18080||18080| |Anti-LAT - 19158||19158| |Anti-LAT - 2043523||2043523| |Anti-LAT - 22622||22622| |Anti-LAT - DAM1522874||DAM1522874| References | 26 Available | See All References |Reference overview||Application||Pub Med ID| |Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. | Roncagalli, R; Hauri, S; Fiore, F; Liang, Y; Chen, Z; Sansoni, A; Kanduri, K; Joly, R; Malzac, A; Lähdesmäki, H; Lahesmaa, R; Yamasaki, S; Saito, T; Malissen, M; Aebersold, R; Gstaiger, M; Malissen, B Nature immunology 15 384-92 2014 T cell antigen receptor (TCR)-mediated activation of T cells requires the interaction of dozens of proteins. Here we used quantitative mass spectrometry and activated primary CD4(+) T cells from mice in which a tag for affinity purification was knocked into several genes to determine the composition and dynamics of multiprotein complexes that formed around the kinase Zap70 and the adaptors Lat and SLP-76. Most of the 112 high-confidence time-resolved protein interactions we observed were previously unknown. The surface receptor CD6 was able to initiate its own signaling pathway by recruiting SLP-76 and the guanine nucleotide-exchange factor Vav1 regardless of the presence of Lat. Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub that contributes to the diversification of TCR signaling. |Assessment of caspase mediated degradation of linker for activation of T cells (LAT) at a single cell level. | Kłossowicz, Mikołaj, et al. J. Immunol. Methods, 389: 9-17 (2013) 2013 Caspase/Granzyme B mediated protein degradation is involved in elimination of activated T cell receptor (TCR) signaling molecules during processes of thymocyte selection and maintenance of peripheral homeostasis of T cells. Key components of TCR signaling cassette including LAT undergo biological inactivation in response to pro-apoptotic or anergy inducing environmental stimuli. Although available Western immunoblotting-based techniques are appropriate for detection of protein degradation in bulk populations of target cells, quantitative assessment of this process at a single cell level requires a different approach. Here we report on a novel, flow cytometry-based method for assessment of LAT integrity. This method exploits a loss of an anti-LAT antibody epitope recognition following proteolytic degradation of C-terminal domain of the LAT. We show that the LAT degradation precedes phosphatidylserine translocation to the outer leaflet of the plasma membrane and thus may constitute an early marker of T cell apoptosis. When used in conjunction with multi-parameter flow cytometry, our method revealed that FoxP3(+)CD4(+)CD8(low) thymocytes i.e. precursors of thymus derived CD4(+) regulatory T cells, in contrast to Foxp3(-)CD4(+)CD8(low) thymocytes are resistant to LAT degradation in response to CD3ε crosslinking. This finding can be used as an additional marker for T regulatory cell lineage. |Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells. | Kim, HS; Long, EO Science signaling 5 ra49 2012 The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require synergistic signals from specific pairs of co-activation receptors, such as CD314 (also known as NKG2D) and CD244 (2B4), which bind to distinct ligands present on target cells. These signals are required to overcome inhibition mediated by the E3 ubiquitin ligase c-Cbl of the guanine nucleotide exchange factor Vav1, which promotes activation of NK cells. Here, we showed that the adaptor protein SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons) was required for this synergy and that distinct tyrosine residues in SLP-76 were phosphorylated by each member of a pair of synergistic receptors. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76 enabled binding of SLP-76 to Vav1. Selective phosphorylation of SLP-76 at these residues was restricted to receptors that stimulated ligand-dependent target cell killing; antibody-dependent stimulation of the Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 mutant proteins showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that combined phosphorylation of separate tyrosine residues in SLP-76 forms the basis of synergistic NK cell activation. |Phospholipase Cγ2 plays a role in TCR signal transduction and T cell selection. | Fu, G; Chen, Y; Schuman, J; Wang, D; Wen, R Journal of immunology (Baltimore, Md. : 1950) 189 2326-32 2012 One of the important signaling events following TCR engagement is activation of phospholipase Cγ (PLCγ). PLCγ has two isoforms, PLCγ1 and PLCγ2. It is known that PLCγ1 is important for TCR signaling and TCR-mediated T cell selection and functions, whereas PLCγ2 is critical for BCR signal transduction and BCR-mediated B cell maturation and functions. In this study, we report that PLCγ2 was expressed in primary T cells, and became associated with linker for activated T cells and Src homology 2-domain containing leukocyte protein of 76 kDa and activated upon TCR stimulation. PLCγ1/PLCγ2 double-deficient T cells displayed further block from CD4 and CD8 double-positive to single-positive transition compared with PLCγ1 single-deficient T cells. TCR-mediated proliferation was further impaired in PLCγ1/PLCγ2 double-deficient T cells compared with PLCγ1 single-deficient T cells. TCR-mediated signal transduction, including Ca²⁺ mobilization and Erk activation, was further impaired in PLCγ1/PLCγ2 double-deficient relative to PLCγ1 single-deficient T cells. In addition, in HY TCR transgenic mouse model, thymic positive and negative selections were reduced in PLCγ1 heterozygous- and PLCγ2 homozygous-deficient (PLCγ1⁺/⁻PLCγ2⁻/⁻) relative to wild-type, PLCγ2 single-deficient (PLCγ2⁻/⁻), or PLCγ1 heterozygous-deficient (PLCγ1⁺/⁻) mice. Taken together, these data demonstrate that PLCγ2 participates in TCR signal transduction and plays a role in T cell selection. |OX40 complexes with phosphoinositide 3-kinase and protein kinase B (PKB) to augment TCR-dependent PKB signaling. | So, T; Choi, H; Croft, M Journal of immunology (Baltimore, Md. : 1950) 186 3547-55 2011 T lymphocyte activation requires signal 1 from the TCR and signal 2 from costimulatory receptors. For long-lasting immunity, growth and survival signals imparted through the Akt/protein kinase B (PKB) pathway in activated or effector T cells are important, and these can be strongly influenced by signaling from OX40 (CD134), a member of the TNFR superfamily. In the absence of OX40, T cells do not expand efficiently to Ag, and memory formation is impaired. How most costimulatory receptors integrate their signals with those from Ag through the TCR is not clear, including whether OX40 directly recruits PKB or molecules that regulate PKB. We show that OX40 after ligation by OX40L assembled a signaling complex that contained the adapter TNFR-associated factor 2 as well as PKB and its upstream activator phosphoinositide 3-kinase (PI3K). Recruitment of PKB and PI3K were dependent on TNFR-associated factor 2 and on translocation of OX40 into detergent-insoluble membrane lipid microdomains but independent of TCR engagement. However, OX40 only resulted in strong phosphorylation and functional activation of the PI3K-PKB pathway when Ag was recognized. Therefore, OX40 primarily functions to augment PKB signaling in T cells by enhancing the amount of PI3K and PKB available to the TCR. This highlights a quantitative role of this TNFR family second signal to supplement signal 1. |Beta-catenin inhibits T cell activation by selective interference with linker for activation of T cells-phospholipase C-γ1 phosphorylation. | Driessens, G; Zheng, Y; Locke, F; Cannon, JL; Gounari, F; Gajewski, TF Journal of immunology (Baltimore, Md. : 1950) 186 784-90 2011 Despite the defined function of the β-catenin pathway in thymocytes, its functional role in peripheral T cells is poorly understood. We report that in a mouse model, β-catenin protein is constitutively degraded in peripheral T cells. Introduction of stabilized β-catenin into primary T cells inhibited proliferation and cytokine secretion after TCR stimulation and blunted effector cell differentiation. Functional and biochemical studies revealed that β-catenin selectively inhibited linker for activation of T cells phosphorylation on tyrosine 136, which was associated with defective phospholipase C-γ1 phosphorylation and calcium signaling but normal ERK activation. Our findings indicate that β-catenin negatively regulates T cell activation by a previously undescribed mechanism and suggest that conditions under which β-catenin might be inducibly stabilized in vivo would be inhibitory for T cell-based immunity. |β2 integrin induces TCRζ-Syk-phospholipase C-γ phosphorylation and paxillin-dependent granule polarization in human NK cells. | March, ME; Long, EO Journal of immunology (Baltimore, Md. : 1950) 186 2998-3005 2011 Cytotoxic lymphocytes kill target cells through polarized release of the content of lytic granules at the immunological synapse. In human NK cells, signals for granule polarization and for degranulation can be uncoupled: Binding of β(2) integrin LFA-1 to ICAM is sufficient to induce polarization but not degranulation, whereas CD16 binding to IgG triggers unpolarized degranulation. In this study, we investigated the basis for this difference. IL-2-expanded human NK cells were stimulated by incubation with plate-bound ligands of LFA-1 (ICAM-1) and CD16 (human IgG). Surprisingly, LFA-1 elicited signals similar to those induced by CD16, including tyrosine phosphorylation of the TCR ζ-chain, tyrosine kinase Syk, and phospholipase C-γ. Whereas CD16 activated Ca(2+) mobilization and LAT phosphorylation, LFA-1 did not, but induced strong Pyk2 and paxillin phosphorylation. LFA-1-dependent granule polarization was blocked by inhibition of Syk, phospholipase C-γ, and protein kinase C, as well as by paxillin knockdown. Therefore, common signals triggered by CD16 and LFA-1 bifurcate to provide independent control of Ca(2+)-dependent degranulation and paxillin-dependent granule polarization. |T-cell receptor microclusters critical for T-cell activation are formed independently of lipid raft clustering. | Hashimoto-Tane, A; Yokosuka, T; Ishihara, C; Sakuma, M; Kobayashi, W; Saito, T Molecular and cellular biology 30 3421-9 2010 We studied the function of lipid rafts in generation and signaling of T-cell receptor microclusters (TCR-MCs) and central supramolecular activation clusters (cSMACs) at immunological synapse (IS). It has been suggested that lipid raft accumulation creates a platform for recruitment of signaling molecules upon T-cell activation. However, several lipid raft probes did not accumulate at TCR-MCs or cSMACs even with costimulation and the fluorescence resonance energy transfer (FRET) between TCR or LAT and lipid raft probes was not induced at TCR-MCs under the condition of positive induction of FRET between CD3 zeta and ZAP-70. The analysis of LAT mutants revealed that raft association is essential for the membrane localization but dispensable for TCR-MC formation. Careful analysis of the accumulation of raft probes in the cell interface revealed that their accumulation occurred after cSMAC formation, probably due to membrane ruffling and/or endocytosis. These results suggest that lipid rafts control protein translocation to the membrane but are not involved in the clustering of raft-associated molecules and therefore that the lipid rafts do not serve as a platform for T-cell activation. |Vitamin D controls T cell antigen receptor signaling and activation of human T cells. | von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C Nat Immunol 11 344-9. Epub 2010 Mar 7. 2010 Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Here we show that naive human T cells had very low expression of PLC-gamma1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering led to an upregulation of approximately 75-fold in PLC-gamma1 expression, which correlated with greater TCR responsiveness. Induction of PLC-gamma1 was dependent on vitamin D and expression of the vitamin D receptor (VDR). Naive T cells did not express VDR, but VDR expression was induced by TCR signaling via the alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38 leads to successive induction of VDR and PLC-gamma1, which are required for subsequent classical TCR signaling and T cell activation. |Targeting of the small GTPase Rap2b, but not Rap1b, to lipid rafts is promoted by palmitoylation at Cys176 and Cys177 and is required for efficient protein activation in human platelets. | Ilaria Canobbio, Piera Trionfini, Gianni F Guidetti, Cesare Balduini, Mauro Torti, Ilaria Canobbio, Piera Trionfini, Gianni F Guidetti, Cesare Balduini, Mauro Torti Cellular signalling 20 1662-70 2008 Rap1b and Rap2b are the only members of the Rap family of GTPases expressed in circulating human platelets. Rap1b is involved in the inside-out activation of integrins, while the role of Rap2b is still poorly understood. In this work, we investigated the localization of Rap proteins to specific microdomains of plasma membrane called lipid rafts, implicated in signal transduction. We found that Rap1b was not associated to lipid rafts in resting platelets, and did not translocate to these microdomains in stimulated cells. By contrast, about 20% of Rap2b constitutively associated to lipid rafts, and this percentage did not increase upon platelet stimulation. Rap2b interaction with lipid rafts also occurred in transfected HEK293T cell. Upon metabolic labelling with [(3)H]palmitate, incorporation of the label into Rap2b was observed. Palmitoylation of Rap2b did not occur when Cys176 or Cys177 were mutated to serine, or when the C-terminal CAAX motif was deleted. Contrary to CAAX deletion, Cys176 and Cys177 substitution did not alter the membrane localization of Rap2b, however, relocation of the mutants within lipid rafts was completely prevented. In intact platelets, disruption of Rap2b interaction with lipid rafts obtained by cholesterol depletion caused a significant inhibition of aggregation. Importantly, agonist-induced activation of Rap2b was concomitantly severely impaired. These results demonstrate that Rap2b, but not the more abundant Rap1b, is associated to lipid rafts in human platelets. This interaction is supported by palmitoylation of Rap2b, and is important for a complete agonist-induced activation of this GTPase. |Caspase-8 and c-FLIPL associate in lipid rafts with NF-kappaB adaptors during T cell activation. | Misra, RS; Russell, JQ; Koenig, A; Hinshaw-Makepeace, JA; Wen, R; Wang, D; Huo, H; Littman, DR; Ferch, U; Ruland, J; Thome, M; Budd, RC The Journal of biological chemistry 282 19365-74 2007 Humans and mice lacking functional caspase-8 in T cells manifest a profound immunodeficiency syndrome due to defective T cell antigen receptor (TCR)-induced NF-kappaB signaling and proliferation. It is unknown how caspase-8 is activated following T cell stimulation, and what is the caspase-8 substrate(s) that is necessary to initiate T cell cycling. We observe that following TCR ligation, a small portion of total cellular caspase-8 and c-FLIP(L) rapidly migrate to lipid rafts where they associate in an active caspase complex. Activation of caspase-8 in lipid rafts is followed by rapid cleavage of c-FLIP(L) at a known caspase-8 cleavage site. The active caspase.c-FLIP complex forms in the absence of Fas (CD95/APO1) and associates with the NF-kappaB signaling molecules RIP1, TRAF2, and TRAF6, as well as upstream NF-kappaB regulators PKC theta, CARMA1, Bcl-10, and MALT1, which connect to the TCR. The lack of caspase-8 results in the absence of MALT1 and Bcl-10 in the active caspase complex. Consistent with this observation, inhibition of caspase activity attenuates NF-kappaB activation. The current findings define a link among TCR, caspases, and the NF-kappaB pathway that occurs in a sequestered lipid raft environment in T cells. |Persistence of cooperatively stabilized signaling clusters drives T-cell activation. | Bunnell, SC; Singer, AL; Hong, DI; Jacque, BH; Jordan, MS; Seminario, MC; Barr, VA; Koretzky, GA; Samelson, LE Molecular and cellular biology 26 7155-66 2006 Antigen recognition triggers the recruitment of the critical adaptor protein SLP-76 to small macromolecular clusters nucleated by the T-cell receptor (TCR). These structures develop rapidly, in parallel with TCR-induced increases in tyrosine phosphorylation and cytosolic calcium, and are likely to contribute to TCR-proximal signaling. Previously, we demonstrated that these SLP-76-containing clusters segregate from the TCR and move towards the center of the contact interface. Neither the function of these clusters nor the structural requirements governing their persistence have been examined extensively. Here we demonstrate that defects in cluster assembly and persistence are associated with defects in T-cell activation in the absence of Lck, ZAP-70, or LAT. Clusters persist normally in the absence of phospholipase C-gamma1, indicating that in the absence of a critical effector, these structures are insufficient to drive T-cell activation. Furthermore, we show that the critical adaptors LAT and Gads localize with SLP-76 in persistent clusters. Mutational analyses of LAT, Gads, and SLP-76 indicated that multiple domains within each of these proteins contribute to cluster persistence. These data indicate that multivalent cooperative interactions stabilize these persistent signaling clusters, which may correspond to the functional complexes predicted by kinetic proofreading models of T-cell activation.Full Text Article |DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production. | Caparrós, E; Munoz, P; Sierra-Filardi, E; Serrano-Gómez, D; Puig-Kröger, A; Rodríguez-Fernández, JL; Mellado, M; Sancho, J; Zubiaur, M; Corbí, AL Blood 107 3950-8 2006 The generation of pathogen-specific immune responses is dependent on the signaling capabilities of pathogen-recognition receptors. DC-SIGN is a C-type lectin that mediates capture and internalization of viral, bacterial, and fungal pathogens by myeloid dendritic cells. DC-SIGN-interacting pathogens are thought to modulate dendritic cell maturation by interfering with intracellular signaling from Toll-like receptor molecules. We report that engagement of DC-SIGN by specific antibodies does not promote dendritic cell maturation but induces ERK1/2 and Akt phosphorylation without concomitant p38MAPK activation. DC-SIGN ligation also triggers PLCgamma phosphorylation and transient increases in intracellular calcium in dendritic cells. In agreement with its signaling capabilities, a fraction of DC-SIGN molecules partitions within lipid raft-enriched membrane fractions both in DC-SIGN-transfected and dendritic cells. Moreover, DC-SIGN in dendritic cells coprecipitates with the tyrosine kinases Lyn and Syk. The relevance of the DC-SIGN-initiated signals was demonstrated in monocyte-derived dendritic cells, as DC-SIGN cross-linking synergizes with TNF-alpha for IL-10 release and enhances the production of LPS-induced IL-10. These results demonstrate that DC-SIGN-triggered intracellular signals modulate dendritic cell maturation. Since pathogens stimulate Th2 responses via preferential activation of ERK1/2, these results provide a molecular explanation for the ability of DC-SIGN-interacting pathogens to preferentially evoke Th2-type immune responses. |The ubiquitously expressed Csk adaptor protein Cbp is dispensable for embryogenesis and T-cell development and function. | Dobenecker, MW; Schmedt, C; Okada, M; Tarakhovsky, A Molecular and cellular biology 25 10533-42 2005 Regulation of Src family kinase (SFK) activity is indispensable for a functional immune system and embryogenesis. The activity of SFKs is inhibited by the presence of the carboxy-terminal Src kinase (Csk) at the cell membrane. Thus, recruitment of cytosolic Csk to the membrane-associated SFKs is crucial for its regulatory function. Previous studies utilizing in vitro and transgenic models suggested that the Csk-binding protein (Cbp), also known as phosphoprotein associated with glycosphingolipid microdomains (PAG), is the membrane adaptor for Csk. However, loss-of-function genetic evidence to support this notion was lacking. Herein, we demonstrate that the targeted disruption of the cbp gene in mice has no effect on embryogenesis, thymic development, or T-cell functions in vivo. Moreover, recruitment of Csk to the specialized membrane compartment of "lipid rafts" is not impaired by Cbp deficiency. Our results indicate that Cbp is dispensable for the recruitment of Csk to the membrane and that another Csk adaptor, yet to be discovered, compensates for the loss of Cbp.Full Text Article |CD45 signals outside of lipid rafts to promote ERK activation, synaptic raft clustering, and IL-2 production. | Min Zhang, Miriana Moran, June Round, Teresa A Low, Viresh P Patel, Tamar Tomassian, Joseph D Hernandez, M Carrie Miceli Journal of immunology (Baltimore, Md. : 1950) 174 1479-90 2005 CD45 is dynamically repositioned within lipid rafts and the immune synapse during T cell activation, although the molecular consequences of CD45 repositioning remain unclear. In this study we examine the role of CD45 membrane compartmentalization in regulating murine T cell activation. We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. We propose that these dual CD45 activities ensure that only robust TCR signals proceed, whereas signals meeting threshold requirements are potentiated. Our findings highlight membrane compartmentalization as a key regulator of CD45 function and elucidate a novel signal transduction pathway by which raft-excluded CD45 positively regulates T cell activation. |T cell receptor zeta reconstitution fails to restore responses of T cells rendered hyporesponsive by tumor necrosis factor alpha. | Clark, JM; Annenkov, AE; Panesar, M; Isomäki, P; Chernajovsky, Y; Cope, AP Proceedings of the National Academy of Sciences of the United States of America 101 1696-701 2004 Expression and function of the antigen T cell receptor (TCR) play a central role in regulating immune responsiveness. Accordingly, targeting the expression of TCRalphabeta or its associated CD3 subunits profoundly influences T cell development and adaptive immunity. Down-regulation of the invariant TCRzeta chain has been documented in a wide variety of chronic inflammatory and infectious diseases, and is thought to contribute to the paradoxical immune suppression observed in these diseases. Previously, we reported that prolonged exposure of T cell hybridoma clones to tumor necrosis factor alpha (TNF) induces nondeletional and reversible hyporesponsiveness to TCR engagement, associated with down-regulation of TCRzeta chain expression, impaired TCR/CD3 complex assembly, and attenuation of TCR-induced membrane proximal tyrosine phosphorylation. Here, we have tested whether receptor specific T cell responses are rescued in TNF-treated T cell hybridomas by retroviral-mediated expression of zeta-chimeric (C2zeta) receptors or wild-type TCRzeta. Expression of C2zeta receptors at the cell surface is relatively refractory to chronic TNF stimulation. However, C2zeta receptor function depends on association with endogenous TCRzeta chains, whose expression is down-regulated by TNF, and so C2 receptor specific responses are attenuated in TNF-treated T cells. Unexpectedly, overexpression of wild-type TCRzeta maintains cell surface TCR/CD3 complex expression but fails to rescue receptor proximal signaling in TNF-treated T cells, suggesting the existence of hitherto unrecognized mechanisms through which TNF regulates T cell responsiveness. We provide additional evidence that TNF also uncouples distal TCR signaling pathways independently of its effects on TCRzeta expression. |Proteome analysis reveals caspase activation in hyporesponsive CD4 T lymphocytes induced in vivo by the oral administration of antigen | Kaji, T., et al J Biol Chem, 278:27836-43 (2003) 2003 |T cell receptor-mediated signal transduction controlled by the beta chain transmembrane domain: apoptosis-deficient cells display unbalanced mitogen-activated protein kinases activities upon T cell receptor engagement. | Teixeiro, Emma, et al. J. Biol. Chem., 277: 3993-4002 (2002) 2002 The bases that support the versatility of the T cell receptor (TCR) to generate distinct T cell responses remain unclear. We have previously shown that mutant cells in the transmembrane domain of TCRbeta chain are impaired in TCR-induced apoptosis but are not affected in other functions. Here we describe the biochemical mechanisms by which this mutant receptor supports some T cell responses but fails to induce apoptosis. Extracellular signal-regulated protein kinase (ERK) is activated at higher and more sustained levels in TCRbeta-mutated than in wild type cells. Conversely, activation of both c-Jun N-terminal kinase and p38 mitogen-activated protein kinase is severely reduced in mutant cells. By attempting to link this unbalanced induction to altered upstream events, we found that ZAP-70 is normally activated. However, although SLP-76 phosphorylation is normally induced, TCR engagement of mutant cells results in lower tyrosine phosphorylation of LAT but in higher tyrosine phosphorylation of Vav than in wild type cells. The results suggest that an altered signaling cascade leading to an imbalance in mitogen-activated protein kinase activities is involved in the selective impairment of apoptosis in these mutant cells. Furthermore, they also provide new insights in the contribution of TCR to decipher the signals that mediate apoptosis distinctly from proliferation. |Effect of redox balance alterations on cellular localization of LAT and downstream T-cell receptor signaling pathways. | Gringhuis, SI; Papendrecht-van der Voort, EA; Leow, A; Nivine Levarht, EW; Breedveld, FC; Verweij, CL Molecular and cellular biology 22 400-11 2002 The integral membrane protein linker for activation of T cells (LAT) is a central adapter protein in the T-cell receptor (TCR)-mediated signaling pathways. The cellular localization of LAT is extremely sensitive to intracellular redox balance alterations. Reduced intracellular levels of the antioxidant glutathione (GSH), a hallmark of chronic oxidative stress, resulted in the membrane displacement of LAT, abrogated TCR-mediated signaling and consequently hyporesponsiveness of T lymphocytes. The membrane displacement of LAT is accompanied by a considerable difference in the mobility of LAT upon native and nonreducing denaturing polyacrylamide gel electrophoresis analysis, a finding indicative of a conformational change. Targeted mutation of redox-sensitive cysteine residues within LAT created LAT mutants which remain membrane anchored under conditions of chronic oxidative stress. The expression of redox-insensitive LAT mutants allows for restoration of TCR-mediated signal transduction, whereas CD28-mediated signaling pathways remained impaired. These results are indicative that the membrane displacement of LAT as a result of redox balance alterations is a consequence of a conformational change interfering with the insertion of LAT into the plasma membrane. Conclusively, the data suggest a role for LAT as a crucial intermediate in the sensitivity of TCR signaling and hence T lymphocytes toward chronic oxidative stress.Full Text Article |Dynamic recruitment of human CD2 into lipid rafts. Linkage to T cell signal transduction | Yang, H. and Reinherz, E. L. J Biol Chem, 276:18775-85 (2001) 2001 |High resolution mapping of mast cell membranes reveals primary and secondary domains of Fc(epsilon)RI and LAT. | Wilson, B S, et al. J. Cell Biol., 154: 645-58 (2001) 2001 In mast cells, cross-linking the high-affinity IgE receptor (Fc(epsilon)RI) initiates the Lyn-mediated phosphorylation of receptor ITAMs, forming phospho-ITAM binding sites for Syk. Previous immunogold labeling of membrane sheets showed that resting Fc(epsilon)RI colocalize loosely with Lyn, whereas cross-linked Fc(epsilon)RI redistribute into specialized domains (osmiophilic patches) that exclude Lyn, accumulate Syk, and are often bordered by coated pits. Here, the distribution of Fc(epsilon)RI beta is mapped relative to linker for activation of T cells (LAT), Grb2-binding protein 2 (Gab2), two PLCgamma isoforms, and the p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase), all implicated in the remodeling of membrane inositol phospholipids. Before activation, PLCgamma1 and Gab2 are not strongly membrane associated, LAT occurs in small membrane clusters separate from receptor, and PLCgamma2, that coprecipitates with LAT, occurs in clusters and along cytoskeletal cables. After activation, PLCgamma2, Gab2, and a portion of p85 colocalize with Fc(epsilon)RI beta in osmiophilic patches. LAT clusters enlarge within 30 s of receptor activation, forming elongated complexes that can intersect osmiophilic patches without mixing. PLCgamma1 and another portion of p85 associate preferentially with activated LAT. Supporting multiple distributions of PI3-kinase, Fc(epsilon)RI cross-linking increases PI3-kinase activity in anti-LAT, anti-Fc(epsilon)RIbeta, and anti-Gab2 immune complexes. We propose that activated mast cells propagate signals from primary domains organized around Fc(epsilon)RIbeta and from secondary domains, including one organized around LAT. |Selective accumulation of raft-associated membrane protein LAT in T cell receptor signaling assemblies | Harder, T. and Kuhn, M. J Cell Biol, 151:199-208 (2000) 2000 |Displacement of linker for activation of T cells from the plasma membrane due to redox balance alterations results in hyporesponsiveness of synovial fluid T lymphocytes in rheumatoid arthritis. | S I Gringhuis, A Leow, E A Papendrecht-Van Der Voort, P H Remans, F C Breedveld, C L Verweij Journal of immunology (Baltimore, Md. : 1950) 164 2170-9 2000 The T lymphocytes that reside in the synovium of the inflamed joints in patients with rheumatoid arthritis display severe hyporesponsiveness upon antigenic stimulation, which is probably due to their constant subjection to high levels of oxidative stress. Here we report that the synovial fluid T lymphocytes exert severely impaired phosphorylation of the adaptor protein linker for activation of T cells (LAT), a crucial component of the TCR-mediated signaling pathways. In healthy T lymphocytes, LAT is a membrane-bound protein and becomes phosphorylated by zeta-associated protein of 70 kDa (ZAP-70) upon TCR engagement. The molecular basis underlying the deficient phosphorylation of LAT and consequently the hyporesponsiveness of the synovial fluid T lymphocytes lies in the membrane displacement of LAT. We demonstrate that the subcellular localization of LAT is sensitive to changes in the intracellular levels of the antioxidant glutathione. The membrane anchorage of LAT, and consequently the phosphorylation of LAT and the cellular activation of the synovial fluid T lymphocytes upon TCR engagement, is restored in synovial fluid T lymphocytes after supplementation of the intracellular glutathione levels with N-acetyl-l -cysteine. These data suggest a role for the membrane displacement of LAT in the hyporesponsiveness of the synovial fluid T lymphocytes as a consequence of oxidative stress. |TCR activation inhibits chemotaxis toward stromal cell-derived factor-1: evidence for reciprocal regulation between CXCR4 and the TCR. | J W Peacock, F R Jirik Journal of immunology (Baltimore, Md. : 1950) 162 215-23 1999 Stromal cell-derived factor-1 (SDF-1), a C-X-C family chemokine, is a potent T lymphocyte chemoattractant. We investigated the effects of T cell activation on the chemotactic response to SDF-1. Anti-CD3 Ab stimulation of either Jurkat T cells or murine peripheral CD4+ T lymphocytes produced a dramatic inhibition of SDF-1-induced chemotaxis. In contrast, the SDF-1 responses of Jurkat clones with deficiencies in key TCR signaling components (Lck, CD45, and TCR-beta), were only marginally reduced by anti-CD3 stimulation. Similar to PMA treatment, which abolished both CXCR4 receptor expression and the chemotactic response of Jurkat cells to SDF-1, anti-CD3 Ab treatment reduced cell surface expression of CXCR4 to 65% of the control value, an effect that was blocked by protein kinase C inhibitors. Our data suggest that initial T cell activation events inhibit the response of Jurkat T cells to CXCR4 stimulation. In contrast, SDF-1 treatment resulted in a reduction of tyrosine phosphorylation of the TCR downstream effectors, ZAP-70, SLP-76, and LAT (linker for activation of T cells), suggesting that this chemokine potentially regulates the threshold for T cell activation. |LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. | Zhang, W, et al. Cell, 92: 83-92 (1998) 1998 Despite extensive study, several of the major components involved in T cell receptor-mediated signaling remain unidentified. Here we report the cloning of the cDNA for a highly tyrosine-phosphorylated 36-38 kDa protein, previously characterized by its association with Grb2, phospholipase C-gamma1, and the p85 subunit of phosphoinositide 3-kinase. Deduced amino acid sequence identifies a novel integral membrane protein containing multiple potential tyrosine phosphorylation sites. We show that this protein is phosphorylated by ZAP-70/Syk protein tyrosine kinases leading to recruitment of multiple signaling molecules. Its function is demonstrated by inhibition of T cell activation following overexpression of a mutant form lacking critical tyrosine residues. Therefore, we propose to name the molecule LAT-linker for activation of T cells. |Activating and inhibitory mutations in adjacent tyrosines in the kinase domain of ZAP-70. | Wange, R L, et al. J. Biol. Chem., 270: 18730-3 (1995) 1995 ZAP-70 is an 70-kDa protein tyrosine kinase, expressed exclusively in T cells and NK cells, and plays a critical role in mediating T cell activation in response to T cell receptor engagement. The strong correlation between tyrosine phosphorylation of ZAP-70 and its acquisition of increased kinase activity suggests that is is positively regulated by tyrosine phosphorylation. Previously, we identified tyrosines 492 and 493 of ZAP-70 as being sites of in vivo phosphorylation in response to T cell receptor engagement. To determine the role of phosphorylation in regulating ZAP-70 activity, we mutated each of these tyrosines individually to phenylalanine. When expressed in COS cells, Y493F-mutated ZAP-70 demonstrated normal basal kinase activity, but, unlike wild type ZAP-70, could not be activated by tyrosine phosphorylation induced by incubation with pervanadate or by co-expression of constitutively activated Lck. This suggests that Tyr-493 phosphorylation is required for the tyrosine phosphorylation-induced activation of ZAP-70. The Y492F mutation resulted in 4-fold higher basal kinase activity, which could be stimulated further by tyrosine phosphorylation. These results reveal that critical tyrosine residues in the kinase domain of ZAP-70 are important in regulation of its catalytic activity.

Everyone knows comparing individual players is fun. But it’s roster fit that’s crucial in determining how effective one player is within a particular team context — and whether that player helps drive success for that team. With those kinds of fit issues in mind, here’s a look at six front-line combinations whose success or failure will have a huge impact on the futures of their respective franchise: Tiago Splitter–Tim Duncan, San Antonio Spurs The importance of this duo, once seldom-used, is simple: The Spurs may need them for a crucial stretch here and there if they want to win the title, particularly if their playoff path includes one of the Western Conference’s bigger front lines — Memphis, Utah, and both Los Angeles teams. It has taken three years of very gradual development, but the Spurs are finally scoring when their two center types share the floor together; San Antonio this season has scored a mammoth 111.9 points per 100 possessions in 127 Splitter-Duncan minutes, a mark that would lead the league by a long shot. A year ago, San Antonio’s league-best offense scored at a bottom-five rate in just 129 Splitter-Duncan minutes, per NBA.com The Spurs with Splitter-Duncan were actually playing stingier defense and holding steady on the boards before the Thunder slaughtered these groups in 13 minutes Monday night. Those 13 minutes brought both the Splitter-Duncan points allowed and defensive rebounding numbers below San Antonio’s overall averages, which shows how small these early sample sizes really are. Still: That these lineups have scored so well is encouraging. The Splitter-Duncan Spurs don’t shoot nearly as many 3s as San Antonio normally does, and that can cramp the team’s spacing a bit. But the team as a whole is adjusting with more varied play calling, whip-smart passing from both bigs, and the developing chemistry between them. They move on opposite north-south planes, so that if Duncan sets a high screen on the left side and rolls to the hoop, Splitter will move up from the right block toward the foul line — flashing for a possible catch and high-low chance with Duncan. The two will sometimes screen for each other, including some Splitter pin-down picks designed to free Duncan for a mid-range jumper, and the coaching staff is smart about having one of them doing something to occupy the defense on the weak side when the other sets a pick for Tony Parker on the ball. The assist rate for these groups is way up, as it is for San Antonio as a whole: The Spurs assisted on about a league-average percentage of their baskets last season, but they’re neck and neck with Chicago for the top spot this season. All this tic-tac-toe passing hasn’t led to a jump in turnovers for Splitter-Duncan lineups, and these big groups are actually fouling less than the always foul-averse Spurs overall. The Splitter-Duncan sample size is still small, and the results are all over the place once you zoom out to five-man units involving the pair. Spacing will be an issue on some nights, and quick power forwards can be a problem behind the arc and on rapid-fire duck-ins down low. But the early trends are encouraging. The Splitter-Duncan front line, and all five highlighted below, are really about seeing whether NBA teams can survive — and even thrive — offensively without the beloved stretch power forward with a shooting range to 20 feet and beyond. Greg Monroe–Andre Drummond, Detroit Pistons This might be the only reason Detroit fans are watching the team, even if it leaves them angry the front line of the future isn’t playing more. Monroe and Drummond have logged only 91 minutes together so far, and you can kind of understand Lawrence Frank’s reluctance. Detroit’s offense, already in the league’s bottom 10, drops off by about five points per 100 possessions — a huge number — when the two bigs share the floor. But the defense improves by about the same amount — the equivalent of jumping from about 20th to fifth overall. Detroit is one of the worst defensive rebounding teams in the league, but when Monroe-Drummond (Mummond?) take the floor, they grab everything in sight, rebounding at a league-best rate on both ends. Drummond is raw, and Detroit struggles to space the floor on offense as it is. Monroe is a minus defender, and the pair are in the very early stages of developing a defensive chemistry — of learning when to switch on the fly, how to time those rotations, and when to help elsewhere. And Drummond plays with a restraint that makes it look as if he’s afraid to unleash his full athleticism, lest he accidentally injure teammates or fans in the first 10 rows. He’s a freak, and once he finds the right balance between freakishness and control, he could develop into a devastating player — and a perfect back-line complement to the ground-bound Monroe on defense. As it is, he’s still figuring out what to do with himself when Monroe works with the ball at the elbow or rolls to the rim on pick-and-rolls. He needs to learn how and when to cut off of Monroe so as not to clog things up; there’s a reason Frank uses Charlie Villanueva as a floor-spacing power forward to break things up. Here’s hoping Detroit falls hopelessly out of it, so we can see more of these two. Taj Gibson–Joakim Noah, Chicago Bulls A.k.a. the “Can we amnesty Carlos Boozer?” duet. Gibson is shooting just 43 percent, including a miserable sub-20 percent figure on mid-range jumpers, and the main question about this pairing was always going to be whether Chicago could score enough to justify cutting Boozer’s minutes — or cutting him altogether, via the amnesty provision. Chicago scored at a league-best rate with the Noah-Gibson duo last season, but most of those 311 minutes came with Derrick Rose running the point. In 282 minutes already this season, Chicago’s 24th-ranked offense is scoring at just about the same subpar rate with Gibson-Noah as it is overall. That’s not great news, but it’s not bad news, either; the Bulls are staying afloat, and with Boozer shooting 47 percent and barely getting to the line, the points are coming at the same rate regardless of who plays. What happens when Rose gets back? And the defense. Holy hell, the defense. Chicago is holding teams to 84.2 points per 100 possessions with the Gibson-Noah front line, a number 12 points stingier than Memphis’s league-leading figure. Gibson and Noah are all extended arms and fast feet, able to cover more ground in Tom Thibodeau’s aggressive schemes than two people should be able to manage. They rebound everything and force turnovers at a scary rate. The chemistry still needs to grow on offense, where Gibson typically hangs around the right side as Noah facilitates from the left elbow or sets a ball screen. The Bulls will sometimes have Gibson space toward the right corner, but he hasn’t been able to hit from there. He’s not on Boozer’s level in terms of flashing to the paint and passing the ball, and the timing is sometimes off on Gibson’s darts to the middle. Here’s Gibson drawing a three-second violation as Noah, fresh off a pick-and-roll, struggles to find a passing lane: And here’s Gibson trying to be a scorer but driving right into a Noah cut: They can make up for this by destroying the offensive glass and outrunning opponents in transition, where Noah’s ballhandling is a huge asset. The Bulls will face a huge tax bill next season if they keep Boozer, and they could have cap room in the summer of 2014 if they amnesty him. Has the Gibson-Noah combo shown enough? Ed Davis–Jonas Valanciunas, Toronto Raptors Your new starting Toronto frontcourt, though Dwane Casey has seldom trusted either to finish close games. These guys are skinny, active, long, fast, and inexperienced; and they produce the kind of interior defense you’d expect when you mix all those ingredients. Valanciunas is prone to overhelping, and his hyperactivity can get him out of balance now and then against skilled post brutes. The Raptors are giving up points at a league-average rate when these two play, an improvement from their bottom-five overall mark, per NBA.com. The questions come on the other side, where Toronto’s offense has fallen off a cliff; the Raps have scored just 93.3 points per 100 possessions in Valanciunas-Davis time, right around Washington’s league-worst mark. (My god, has Washington’s offense been horrid.) Davis and Valanciunas are not jump-shooters, and the lane can get very cramped when they play together — a problem that wouldn’t be quite as serious if Toronto’s perimeter players were healthy. Casey has tried to manufacture that spacing by having them set up as opposite elbows, with one working as the hub of the offense — as screener or passer — while the other works with a shooter on the weak side. This marks a huge expansion in duties for each guy, and Davis has shown more aggression sliding into post position on the left block as Valanciunas rolls down the right side on a pick-and-roll;1 Davis has a nice turnaround lefty hook, and though the results have been uneven, he’s on a roll right now and has already taken half as many post-up shots as he attempted all of last season, per Synergy Sports. He’s in the top-30 overall in PER and taking a more active part in Toronto’s offense. All good signs, even if both Davis and Valanciunas need to work on avoiding near-collisions in the paint. Al Jefferson–Derrick Favors, Utah Jazz Jefferson and Paul Millsap will both be free agents this summer, and with Favors and Enes Kanter onboard, it makes sense for Utah to pick just one — especially since the Jazz can re-sign one and still have max-level cap room leftover.2 But which one? The same choice could apply at the trade deadline, should Utah decide to move one outgoing free agent for assets it could use this season or in the future. Favors has played many more minutes with Jefferson than with Millsap, with the idea that his shot-blocking and quickness could cover up Jefferson’s plodding pick-and-roll defense. It worked last season, when the Jazz were much stingier with this pairing, but on the surface, it hasn’t done the trick this season; the Jazz are surrendering an untenable 112.2 points per 100 possessions — far worse than the league’s worst defense. Opponents are lighting up these groups with a 40 percent-plus mark from deep, and they are earning even more foul shots than the always foul-prone Jazz give up overall. The offense is worse, too, with Favors struggling at times to figure out how to be of use during Jefferson’s post-ups on the left block. His mid-range jumper is unreliable, though he has shown an ability to flash into the lane, catch, and make little 10-footers. The timing on those cuts can sometimes be off, especially since Utah’s wings, especially Gordon Hayward, also like to cut to the hoop around Jefferson post-ups. Favors still hasn’t polished his timing when he catches near the foul line and has a step or two to take before arriving at the rim; he reminds me of a less experienced Serge Ibaka in that way. Still: Favors is an explosive athlete and decent pick-and-roll screener, and this setup worked last season. More encouraging: Opponents have done most of the scoring damage when Jefferson and Favors play with Millsap in ultra-big lineups; the two most-used such groups have both allowed more than 125 points per 100 possessions. Remove Millsap, and Utah is defending at an acceptable level with just the other two bigs. Downside: The offense has dipped far below the league’s average without Millsap’s jack-of-all-trades game. The jury’s out on whether Favors-Jefferson will be the foundation of a functional, well-spaced offense this season. But how much does this season matter for Utah, assuming they at least make the playoffs? Brook Lopez–Reggie Evans, Brooklyn Nets This appears to be Brooklyn’s new starting big-man combo, with Kris Humphries losing favor with Avery Johnson and the Nets concerned about their defense — ranked 18th in points allowed per possession. They’ve been even worse than that when Lopez pairs with Humphries and/or Deron Williams; only Brooklyn’s bench has kept it from being one of the two or three worst defensive teams in the league. Solution: Bring the wackiest ingredient on that bench into the starting lineup. Even two years ago, it would have been strange to think of Evans as some sort of defensive specialist. He’s always been an elite rebounder, but his hyperactivity hurt as much it helped on defense. He would often lunge himself far out of position while flying around the floor. He’s more controlled today, but still mobile, and the Nets are betting that mobility can stabilize Brooklyn’s defense. The more ground Evans can cover, the less Lopez must negotiate. Lopez has been a much stronger presence at the rim this season, but he’s still slow in rotating and inconsistent in guarding the pick-and-roll.3 Things are working so far, though Lopez and Evans have logged only 90 minutes together, per NBA.com. The Nets have allowed just 92.4 points per 100 possessions in those minutes, a massive drop-off from their overall number and a stingier mark than the league’s best defenses give up. Evans’s communication skills have also helped. The cost has come on offense, but it has not been huge: The Nets have scored 101.3 points per 100 possessions with Lopez-Evans, a league-average mark, even if it represents a step back from Brooklyn’s top-10 overall number (103.8). Evans has essentially zero offensive skills beyond rebounding and setting picks, and his man will rove all over to disrupt more dangerous stuff.4 When Evans’s guy drifts into help mode, that often leaves the other big-man defender to “zone up” between Evans and Lopez in an attempt to cover both guys. Lopez must take advantage of those moments by flashing into open space for short-range catch-and-shoot chances, as he did several times during Brooklyn’s loss Saturday at Chicago: Even if Evans is no longer the starter, Johnson will likely lean on the Lopez–Evans pairing for meaningful minutes — including in crunch time. It’s hard to start such a one-dimensional player, but the other four starting Nets are all serious scoring threats. Maybe this can work. 10 Things I Like and Don’t Like 1. The Kings’ Transition Defense Oof. Only five teams have given up more fast-break points per game, and the Kings rank in the bottom half of the league in points allowed per possession on those chances. All their wings, especially Marcus Thornton, have a tendency to watch shots when opponents are a step into their run-outs, and Thornton compounds things with some ill-timed crashing of the offensive glass. DeMarcus Cousins running back on defense is a totally different player than Cousins sprinting from defense to offense, to the point that it’s almost embarrassing. This has been a recurring problem for the Kings, a team that just can’t seem to get any better. 2. The Kings’ Purple Road Uniforms One of the sweetest road unis in the league and one that emphasizes a color few teams feature. Their black roadies are nice, too, but these babies stand out. 3. Ian Eagle and the Nets’ Broadcasting Team Eagle’s Seinfield riff on Joe Johnson’s Friday-night buzzer-beater (“That was real, and that was spectactular!”) got a lot of attention, but Eagle is good for a few laugh-out-loud lines every game — including some deadpan stuff at his own expense. In Brooklyn’s home loss to Minnesota in November, Eagle introduced the audience to Greg Stiemsma by noting Stiemsma is not much of a jump-shooter. Before Eagle even finished his sentence, Stiemsma launched a jumper that went in. Eagle cut himself off without missing a beat: “And I take it back.” After another Stiemsma jumper, Eagle began waxing about Stiemsma’s “sweet stroke,” as if it were the stuff of legend. The rest of the team — Greg Anthony, Jim Spanarkel, Ryan Ruocco, Mike Fratello, and Sarah Kustok — are all informative and even-handed. The Nets might have the league’s best all-around broadcasting experience, refreshingly free of homerism. 4. Miami’s PA Announcer His name is Michael Baiamonte, and he is apparently a very nice man. Judging from my Twitter feed, Miami’s fans — his target audience — seem to like him. But some of his calls after Miami baskets, especially those by Chris Bosssssssssshhhhhhhhhhh and Dwyyyyaaaaaaaaaaane Waaaaaaaaaaaaaade, take so long, they are still going on when an opponent scores on the other end. God forbid Wade hits “for threeeeeeeeeeeeeeeeeee.” There is a middle ground between extreme showmanship and boring in-arena entertainment, right? 5. Gordon Hayward’s Stalled Pick-and-Roll Game Hayward last season had a tendency to go nowhere on his wing pick-and-rolls, and to turn the ball over when he tried to do something more aggressive. Nothing has changed this season. Hayward has shot just 8-of-29 on pick-and-rolls, and he has turned over the ball on a whopping 24 percent of all such plays he’s tried, according to Synergy. The rest feature a lot of dribbling and very little north-south progress. Hayward has the superficial look of a decent pick-and-roll option, and the Jazz are surely hoping for more. 6. Rudy Gay’s Vaguely Jordanian Isolation Plays I should dislike them, since they are low-percentage shots, but damn if there isn’t something athletically hypnotic about Rudy Gay’s turnaround jumpers from the post. The motion is just so fluid, and those long arms reach so high in the air the shot is basically unblockable. That’s especially true because Gay seems to do the Michael Jordan thing where he’s still hanging at the apex of his jump when the defender begins falling back toward the floor. Not many shots look more impressive. 7. Stretching Greg Monroe Monroe has always been a skilled high-post passer, but this season Detroit is asking him to do more by stepping up the pace of some sets that feature Monroe at the elbow. One favorite: Detroit will run a pick-and-roll on one side of the floor using the non-Monroe big man — usually Jason Maxiell — to set the screen and roll to the hoop. As Maxiell rolls, Monroe will flash from the baseline up to the elbow on the opposite side of the floor, catch a pass from Detroit’s point guard, and fire an immediate bounce pass to Maxiell near the hoop. It’s Lawrence Frank’s way of using Monroe as a pick-and-roll middle man, doing the work Brandon Knight isn’t ready to do consistently. Good stuff. 8. Kevin Seraphin’s Allergy to Free Throws Seraphin is an intriguing prospect, but the Wiz have to teach this guy to draw some contact. Seraphin has used 25.4 percent of Washington possessions while on the floor via a shot, drawn foul, or turnover. He has attempted 16.6 field goals and just 1.2 free throws per 36 minutes. He is 10-of-17 from the line, total. If he keeps this up, he has a shot to make some NBA history. Only one player has ever played 1,000 minutes in a season, used 25 percent or more of his team’s possessions, and attempted fewer than 1.5 free throws per 36 minutes: Eddie House on the 2005-06 Suns. 9. Andre Iguodala’s Knee Brace It’s yellow-gold, the same color as the trim on Denver’s powder-blue road uniforms. Iguodala’s not the first Nugget player to use accessories in that color, but the lack of originality doesn’t change the fact that it looks good. When all the games start to blend together over the winter, every little idiosyncratic touch helps. 10. Ryan Anderson Threat Level I could do an entire post on the creative ways Monty Williams gets Ryan Anderson open looks in the half-court, but this is more fun. Anderson is now the league’s premier long-range bomber, tossing up a ridiculous eight 3s per game and making a just-as-ridiculous 43.5 percent of them. Teams are absolutely terrified of leaving him open; Ray Allen may be the only player who inspires the same level of fear even before the ball has reached his hands. The best is in semi-transition, when defenses are scrambling to find the right matchups and Anderson is sprinting to an open spot somewhere behind the 3-point arc. There is a wonderful slice of time when the defense — coaches, players, trainers, fans behind the bench, people watching on TV — all realize where the ball is about to be passed, and that it is too late to do anything about it. It is the NBA’s new silent scream.

Bears General Manager Phil Emery took an hour Tuesday to explain the inner workings of the Chicago Bears to the media. But it took him just one season to fire Lovie Smith after nine years as coach of the Chicago Bears. "To get to be a championship team, to win it, we have to be in it more often," Emery explained, noting the Bears made just one trip to the playoffs in six seasons. Emery said the decision was based on Smith's entire body of work. He said that while the playoffs are important, making a deep run consistently is what was missing. "As a professional sports team and as a historic charter member of the greatest sports league in this world, the NFL, our number one goal always has to be to win championships, and to win championships we must be in contention on a consistent basis and to be in contention we have to be in the playoffs on a consistent basis," said Emery. Emery approached Bears Chairman George McCaskey and team President Ted Phillips who told him the firing of Smith was his call. It was an emotional decision felt in the front office. "It was very difficult. Our family has high regard for Lovie," McCaskey said. "He's been high character all the way through. He's represented the Bears very well." McCaskey said Smith didn't just teach Bears players how to play football, he taught them how to be men. Phillips said Smith felt he let the Bears owners down. "There was a sense of appreciation that he had nine years to get the job done," Phillips explained. "And I know that he failed in bringing a championship to the McCaskey family and that was a genuine feeling." Who will be next to try and follow in the footsteps of George Halas? That too will be Emery's call. The GM will conduct interviews and present the finalists to McCaskey and Phillips for a group decision. "I'm looking for a person that has excellence in his role; a leader. Someone who is highly organized and thorough in their approach" Emery said. College ranks or the NFL, Emery will leave no stone unturned. It's all about the synergy ... and the playoffs. "We want to win now. We want to be in that championship now. We want to win that championship now," he said.

Thank you for visiting the Truth Be Told blog. Click here for our website with videos and information on programs. Find out how to volunteer, donate, and attend a graduation. by Lindsey Lane In January 2016, I travelled to the Gatesville Prison with Carol Waid to be a facilitator in training for Truth Be Told’s Talk To Me Writing Class. I was familiar with the prison system as I had gone behind the fence as a journalist and novelist, but this time, with TBT, I would be in service to the women of the Lane Murray Unit by helping them tell their stories. (In the classroom next to ours, Christina Wisdom and Julie Wylie were facilitating the Talk To Me Speaking class.) Because I was completely new to TBT, Carol asked me to experience the class as a newcomer, like the women did: Doing the homework, telling my story, sharing my life. At first, I felt like I didn’t belong. I’m outside the fence. I have freedom. But I am also a woman an a mother and, just as I was hungry to hear their stories, they were eager for mine. We wanted to connect. We wanted to understand one another. We wanted to share. We wanted to heal through telling the truth about our lives, however different they are. One of the most beautiful parts of the Talk To Me Writing and Speaking classes comes near the end of the eight weeks. Our homework is to write one or two sentences about each member of our class and how we see them. It is an opportunity to reflect on how each person has revealed their hearts over the last eight weeks. This is what I said about one class member named LaVerne: I can imagine coming to Miss LaVerne’s home (that’s what I would call her: Miss LaVerne) and drinking slightly sweet tea with a hint of lavender, I think. I try to get her to tell me what the secret ingredient is but Miss LaVerne only smiles. We talk about the weather and other sweet things, “The Blessings,” she calls them. Miss LaVerne knows there is plenty of meanness in the world but she likes to talk about “the blessings that bind us.” After the Speaking and Writing classes were complete, we joined the two communities together. In the first eight weeks we were looking into our pasts and focusing on how we got to our levels of incarceration. The next six weeks is called Discovery – discovering the women we want to become. Near the end of Discovery we began planning our graduation. Each of us would share something we created as a result of being in the classes. LaVerne was stumped about what to contribute. Someone in the class suggested she write a poem. LaVerne said, “Can it be about lavender? I like what you said about lavender.” Here is what she wrote and shared with us at graduation on May 26, 2016. by LaVerne F. True happiness only comes from fearing God and keeping His commandments. Our happiness depends upon the habit of mind that we cultivate. I say let’s practice happy thinking. Every Day. Again I say let’s practice happy thinking every day. Let’s cultivate the merry heart. Let’s develop the happiness habit, and I believe life will become a continual feast for us. Lavender, to most people, is a color. To me, Lavender is beautiful and fragrant, and it is widely known as an essential oil that brings about calming and restful energy as well as evoking a feeling of happiness…Lavender, again I say Lavender. As a result of experiencing this work, I signed up to return to the Lane Murray Unit with Carol Waid to co-facilitate Living Deeper and Freer, which is a continuation of TTM Writing and Speaking classes. Twelve women from the original twenty-eight (some were released, some were transferred to other prisons, and others went to the faith-based dorm) continued on with us. We are a tightly woven community committed to exploring how to live deeper and freer on both sides of the fence. There is so much beauty behind the fence. Truth Be Told allows the women to become more than the crime that put them there. And the next time you smell Lavender, think of LaVerne and cultivate the happiness habit. Please join us Thursday, October 27th, as we Celebrate and Witness stories of women who, through vulnerability and self-awareness, have transformed their lives. The evening will be emceed by Shayla Rivera, and Austin’s own Sara Hickman will give a special performance as we honor Nathalie Sorrell, Co-Founder of TBT, and the many women who transformed their lives by participating in the behind and beyond bars programs. Come and join us as we honor the impact of Truth Be Told’s Work! When: October 27, 2016, 6pm – 9pm Where: Asian American Center – 8401 Cameron Rd., Austin, Texas 78754 (open in Google Maps) Have you ever asked the question, “Do I matter?” These thoughts roamed fiercely through Shana, a participant in our class at the Lane Murray Facility. Shana joined the Talk to Me Speaking class in 2013 and is currently participating in her 5th class with us. She has been a Mentor for 3 of these classes and through these last 2 ½ years she has grown more comfortable with a deep knowing that she matters. Here is her poem: by Shana H., Mentor Way back when, in Yesteryear I lost all the things I held dear Full of hate and lies and fear Pushed all back, not one came near Holding both my fists real tight I’d scream, I’d yell “Can’t break me, not tonight!” I ran from you and I ran from me My pain running deep But you never would see So all alone, I was running scared Didn’t realize people still cared Little did I know the things we all shared Low self-esteem, low self-worth thinking I’m nobody, ever since birth After all was said and done Thinking my wrecked life was no fun Took a life to save my own Could not understand Could never have known; The torn part of my heart inside That fought so hard, had also died Received a term behind bars No more moon, no more stars How do I live inside this place? I cannot stand my very own face something I’ve not seen before Right over there, on the board, by the door I know that signing up is What I need to do Change my life and Become brand new It’s Good. It’s Real. It’s Bold! Yep, you guessed, it’s Truth Be Told How awesome it is to know it’s true I can change and so can you! Give it a chance and you will see Forgiveness, love and community Growing strong with new friends here Showing me what’s real Teaching me what’s dear I can live in the now Not scared and alone Not stuck anymore in Written by Leigh Camp I attended Truth Be Told’s most recent graduation as a respectful witness. It was my second time to be a respectful witness with Truth Be Told, and my second time in a prison, ever. Both events took place at Lockhart Correctional Facility. When I went to the first graduation, the prison had just undergone a management change and was in the process of receiving a major facelift. At this second graduation, the improvements were markedly visible — inspirational quotes cover the freshly painted walls, creating a warmer, more cared-for environment than the prison I’d entered on my first visit. Lockdown lifted just in time. The prison had been in lockdown the past few days. Lockdown is a “surprise” routine procedure that happens a couple times a year. During lockdown, the inmates have to remain in their cells (except to shower) while the officers search the entire facility for contraband. We’d been in limbo about whether or not the event would take place for a couple of days. As co-founder Carol Waid pointed out via email, it was a great exercise in experiencing some of the uncertainty and lack of agency the women who attend TBT classes face every day. We received word from the warden around 1 p.m. — Lockdown was over and graduation was a go! Settling in and making introductions. About twenty-five witnesses attended the graduation with me. We waited for the graduating classes in a room usually used during visitation hours. Katie Ford, a longtime TBT volunteer who taught one of the graduating classes, instructed us to leave empty chairs between us so that the women could sit with us in the audience. That way we’d all be in it together, experiencing the moment as one group. The woman who sat next to me told me that she was nervous. Because of lockdown, she and her reading partner hadn’t had as much chance to practice. Her partner walked in about then and sat down in the chair in front of me. “Can you copy this out?” she asked my neighbor. “Yes, now, I want us to both have a copy to read from! Please.” It was clear they were close friends. The woman sitting next to me just rolled her eyes, grabbed the sheet of paper, and started writing. When she was done, I asked her if she’d known her friend long. “Oh, yes. We’re both diabetics, so we go to a lot of stuff together.” Katie announced it was time to start and the sound of conversation was replaced by a silence filled with a combination of anticipation and nervous energy that was palpable. The pair in front of me were fifth on the list, but the time passed quickly and before they knew it they were up! I patted my neighbor on the back as she walked by. “You’ll do great!” And they did. Theirs was a side-by-side titled “Letting Go.” In it they alluded to the painful experiences they had endured that eventually led them to prison, and described the freedom they had found by accepting those realities and moving past them, into the present. Other stories had titles like “Live Day by Day,” “Shy No More,” “Fear,” “End of the Road,” and “Phoenix Rising.” Each described the women’s personal journeys of reflection and growth through creative expression and connecting with their fellow inmates in a way that was vulnerable, and inherently not how relationships in prison typically work. I was in turn moved, saddened, and strengthened. One woman chose to sing her story, taking the mic and belting it out with true feeling that I’m certain reverberated in each of our beings. The audience punctuated the end of every reading with resounding applause and the women returned to their seats with sounds of “good job!” “well done!” “way to go!” echoing in their ears. At the conclusion of the stories, the women lined up to receive their certificates. Every one of the women had completed all sixteen-weeks worth of classes, along with extensive coursework after hours. That coursework included the very difficult task of self reflection, digging up painful past experiences, examining them, and acknowledging them while not letting them define the course of what happens next. To graduate was truly an achievement, and the pride showed in their eyes as they returned to their seats with their certificates in hand. At the end of the graduation, the respectful witnesses are invited to share how the women’s stories have affected them. We circle up, and one volunteer stands in the middle of the circle at a time and talks into the mic. We took turns talking about how touched and humbled we felt by the women’s stories and commended them on the bravery required to share such deeply personal emotions and experiences. Once it was our turn to be on the mic, we experienced some of the same jitters and butterflies the women had had to overcome as part of their graduation ceremony. It takes guts to speak to a crowd of strangers. If, as volunteers, we didn’t fully realize it while the women were performing, we were made aware of it while we ourselves were the focus of so many eyes. What they gave to me. The graduation ceremony is for women who have made a commitment to complete a course that’s not only difficult, but darn near impossible. They’re asked to be open fully with one another, to expose their deepest fears, lowest moments, greatest hopes…all in an environment that’s constantly telling them to let no one in, to keep their heads down and their guard up. As a respectful witness, my job was just to listen to the product of their journeys and demonstrate my support of their efforts to become the greatest version of themselves. But in doing only that, I gained so much that I feel guilty it may not have been a fully even trade. Meeting these women and hearing their stories gave me a deep appreciation for everything I take for granted. We’ve all made mistakes. We are imperfect people. The difference between their mistakes and my mistakes is that mine have not yet taken away my freedom. On the drive back, I thought about how nice it was that I could drive from Lockhart to Austin, listening to whatever I chose, and arrive at my apartment, and take a bath or read a book or do laundry or do all three without asking anyone’s permission. And all of those ordinary things became extraordinary to me. I was both humbled and inspired by the women who graduated. Humbled by their bravery, and inspired to dig deep into my own story and come out more whole on the other side. Interested in being a respectful witness? If you would like to attend a Truth Be Told graduation as a respectful witness, please contact Carol Waid at firstname.lastname@example.org. Please stop for a moment to ask the following 3 questions: Who has or is currently impacting you? What has or currently is impacting you? Who have you impacted or are currently impacting? The concept of impact seems to be at the forefront of our nation. Thus, I thought it was fitting to write my first blog on it. Impact as a verb, is defined, according to Merriam-Webster dictionary as “having a strong effect on someone or something” or “to hit (something) with great force.” How true the definition is; at least for me. The synergy I experienced during my first 3 weeks with Truth-Be-Told (TBT) was meaningful and eye-opening! I was deeply honored and humbled to listen to the stories of both incarcerated and formerly incarcerated women. I was touched by their willingness to share openly with a complete stranger. They are acutely aware of the stigma, negativity, and judgment associated with incarceration. I witnessed their courage, strength, resilience, creativity, and talents in addition to their pain and sorrow. They owned the decisions they made that led to their sentences and began making amends with their pasts while sharing hopes for their futures. I also witnessed their gratitude and respect for the program facilitators who played a pivotal role in guiding them to speak their truths and reclaim who they are as women and human beings. Support both behind and beyond bars is pivotal for the women. They learn to trust and rely on each other. Successes are celebrated and challenges especially with re-entry are shared. The women possess a determination to succeed even when they experience frustration, disappointment, and struggles. I learned some will experience re-incarceration while others persevere like the graduate of the TBT program whose college graduation I attended. This is the impact TBT has on them and the impact they have on us. On October 27th, TBT will hold its fundraiser. During this event we will be honoring co-founder Nathalie Sorrell for her instrumental, profound, and continual impact on the organization. Her desire to actively minister to women created the momentum that established TBT with her co-founders Carol Waid and Suzanne Armistead. The impact created, I believe, will resonate in the responses given if you ask individuals who served as respectful witnesses at graduations, the staff at the facilities in which the programs are held, and the program participants, themselves. A friend posted to Facebook a photo that had a male wearing a graduation gown and cap holding a sign that read “California spends $9,100 per year to educate me.” Standing beside him is a female wearing an orange jumpsuit holding her sign that reads “California spends $62,300 per year to lock me up.” I wonder how much Texas spends on education and incarceration. According to TDCJ, as of March 2016, TX facilities are comprised of 11,631 (8.1%) female inmates. I wonder what the overall impact would be if the focus centered on education, empowerment, and successful re-entry for the incarcerated population. TBT has begun this work and seeks allies and supporters in continuing the impact. In closing, please consider how you would like to be involved with TBT. Do you enjoy writing and want to be a blog member? Do you enjoy interacting with others in group formats and want to be a program facilitator? Do you enjoy serving on boards and want to be a board member? Do you enjoy sharing information and want to help bring awareness to TBT in our communities? Do you enjoy fundraising, marketing, and/or social media and want to help in these areas? Do you want to give? Do you know others who have the talents, desires, and passion to be involved? Your involvement, in whatever form, will be impactful. Thus, I invite you in joining TBT in creating a long-lasting and meaningful impact on the women we serve and the communities in which we are members. I may be reached at email@example.com. Don’t forget to follow us on both Facebook and twitter @TruthBeToldnews. “Loving ourselves through the process of owning our story is the bravest thing we will ever do.” ~ Brené Brown Thank you for being a part of our Truth Be Told family! Your commitment to our work enables us to change the lives of incarcerated women, their families and their communities. We thank you for your generous contribution and encourage you to read the powerful statement of one of our graduates, so you can feel first-hand how your support impacts these women. by Donna Norman Almost five years ago, I was lost and broken. I was facing my freedom, and it was coming fast. I was so hurt and so angry with everyone and everything, but most of all myself. The choices I made cost me my freedom and the loss of everything that meant anything to me – including and most importantly, my children. I wasn’t ready for my freedom or to face the memories I had to go home to, memories I ran from for seven years. What if I made the same mistakes? What was my purpose going to be now? What did I really have to live for anymore? Then I saw the posters for the Truth Be Told class. I even knew some of the people who had taken the previous class. Everyone loved it and talked about how it made them feel. I didn’t want to open up to strangers, but I was still facing going home with no answers and a broken heart. I thought that this might be my last chance, so I signed up. I was touched by how loving the women of Truth Be Told were; I just wasn’t ready to let them in. I was in Ms. Nathalie’s class, so I had to give a speech on my story. I was dreading it and even thought about dropping out, but that would leave me with my broken heart. I asked myself, “What did I really have to lose by telling my story?” So I started working on it, piece by piece. Surprisingly, I started understanding myself by looking in from a third party perspective. Then the day came for my speech. Ms Nathalie brought some Toastmasters in to critique our speeches, and one of them happened to be her husband [Jim Walsh]. I wasn’t comfortable with a man being there while I was so vulnerable, but I had already come this far. I stood up and started telling my story, although it took every piece of strength I had. Ms. Nathalie’s husband then had the honor of judging my speech, but I feared he was really judging me. I could feel the defiance boiling up inside me, not wanting to hear a man tell me I’m not good enough after hearing me talk about all the other men who have hurt me in every way possible. But to my utter disbelief, he stood up in front of me, looked me dead in my eyes, and apologized for everything those other men had done. Hearing that touched me deep down in my soul. The wall I built so strong to keep everyone else out shattered and the tears wouldn’t stop. I wasn’t being judged… I was being heard. That was when the healing began. Truth Be Told gave me my life back. They helped me understand why I made the decisions I made, not blaming others but understanding them. They helped me change my thinking and be a better, stronger person. I have been home for four years now. I use the tools I learned from Truth Be Told in my everyday life. Although things are hard at times, I haven’t failed or given up, because of what the women of Truth Be Told have given me…my truth. We are a true community of women. In my times of weakness I reach out to them, and they never let me down. I keep my three-year quilt close. Anytime that I need to feel supported I wrap it around me and I see all their smiling faces. The world needs more selfless people like the facilitators with Truth Be Told. They are my angels. Thank you so much, Donna, for sharing your beautiful story, and thank you, Jim Walsh, for being the kind and loving man that you are. Readers, we thought you might want to see a poster that Truth Be Told used to invite women in prison to learn about and sign up for Talk To Me classes. Have you ever wondered what it’s like to experience a Truth Be Told class? In April, Truth Be Told volunteer facilitators Katie Ford and Ginger McGilvray will host a day-long workshop inspired by the Talk to Me classes they lead in prison on behalf of Truth Be Told. Body Stories, a workshop in authentic movement and expressive writing, is slated for Saturday, April 16, from 10 am to 3 pm, at the Still Waters Retreat Center. A portion of the workshop’s proceeds will be donated to Truth Be Told. “We hosted the first Body Stories workshop in August last year, and the experience was downright magical for me,” says Katie. “It’s my dream to bring the restorative work we experience behind bars through Truth Be Told out here in the free world. Body Stories is part of that dream. One thing I’ve come to understand is that you don’t have to be incarcerated to benefit from doing this kind of work. Being human is the only prerequisite.” Body Stories offers four hours of guided practice in authentic movement and expressive writing. Each participant will receive a plantation paper journal and a pen. A healthy lunch will be served midday. “We’re limiting this workshop to 20 participants to ensure quality instruction and depth of practice,” Katie says. “I encourage anyone who desires time for reflection and creativity in a beautiful, rural setting to join us. It’s an opportunity to invest in yourself while supporting a great organization.”

Prime Minister Narendra Modi has asked the health ministry to set up mechanisms to link both Centre and State governments’ numerous health care schemes and to ensure more accountability for doctors and health officials in the public sector. “In order to achieve the desired goal of health for all, there is a need to substantially improve the efficiency of existing mechanisms and schemes,” the prime minister said while chairing a meeting on healthcare. Giving the example of insurance, he called for establishing synergy in all schemes for the health sector being run by the central and state governments. Reviewing the progress of key health indicators such as under-five mortality rate and Maternal Mortality Ratio, Modi asked for specific identification of worst-performing districts, and even within them, particular blocks which required maximum attention. He said these areas should be targeted in a two-pronged approach — prioritized health intervention and appropriate social interventions — to dispel local beliefs and customs that may be hindering progress. Espousing innovative methods of creating health awareness, the prime minister said animation films should be shown to women in health centres immediately post-delivery, to promote good health and nutrition habits. He said simple technology interventions such as SMS should be used to reach ASHA workers across the country on a real-time basis. Modi said the effects of ‘Swachhta Abhiyan’ (clean India initiative) should also become visible in hospitals and public health facilities across the country. The prime minister also asked for a comprehensive audit of all medical equipment in public health facilities. Describing Yoga as one of the most-effective preventive health mechanisms, he asked the health ministry to draw up plans for International Yoga Day on June 21. Expressing acute concern about the prevalence of diseases like encephalitis, especially among children, he asked officials to prepare a roadmap to tackle such diseases, just like natural disasters and other national calamities are tackled. Modi also called for institutionalizing a comprehensive database, containing individual health records, which could be eventually linked to the Aadhar system.

Insulin resistance (IR) and central obesity at midlife are associated with cognitive decline and greater risk for developing Alzheimer's disease (AD). Converging evidence suggests amyloid and neural injury mediate this effect. Yet, the impact of IR and central obesity on the brain remains poorly understood in humans, especially at the preclinical stage of the disease. The objective of Project 2 is to determine the effect of IR and central obesity on longitudinal brain and cognitive change in people at risk for AD. Our overall hypothesis is that central obesity and IR affect multiple pathways which ultimately contribute to a critical burden of neural pathology manifesting as cognitive decline. Our hypothesis is based on our own pilot data (presented herein) showing that central obesity and IR affect amyloid deposition, gray matter atrophy, glucose metabolism, and memory function. To carry out our objective and test our hypothesis, we propose 3 Specific Aims: 1) Determine the extent to which IR and central obesity are linked with midlife beta amyloid, 2) determine the effect of IR and central obesity on neural health in late-midlife, and 3) determine the mediating effect of amyloid and neural injury on memory function. We will achieve these aims by enrolling 100 participants from the Wisconsin ADRC IMPACT cohort into Project 2. The IMPACT cohort is an asymptomatic group of middle-aged adults enriched on risk for AD. We will utilize existing data and samples, in addition to prospectively collected MRI (T1- weighted), CSF (to be assayed for P-Tau, A?42, sAPP-?, and insulin) cognitive, laboratory and clinical data; culminating in at least three time points. Half of the participants in Project 2 will be enrolled into a PET sub- study and will undergo [F18]FDG-PET, and [F18]Florbetapir imaging at two time points. Following completion of this study, we will have a) determined the extent to which IR and central obesity affect the ?-secretase pathway of APP cleavage, and longitudinal amyloid deposition, b) determined the effect of IR and central obesity on longitudinal brain amyloidosis as indexed by [F18]Florbetapir, c) determined the effect of IR and central obesity on structural neural injury and glucose uptake, d) determined whether glucose hypometabolism is due to neural injury or central hypoinsulinemia, and e) determined the extent to which amyloid and neural injury mediate the relationship between IR, central obesity, and hippocampal-based memory decline. The proposed research is fully integrated with the resources and expertise at the Wisconsin ADRC. This project depends on the Clinical Core (IMPACT cohort) and the Neuropathology Core (fluid sample management), and will utilize other resources including services provided by the Neuroimaging Core and the Data Management and Statistics Core. Synergy with the Wisconsin ADRC ensures the strong feasibility of the proposed research. The metabolic abnormalities to be studied in Project 2 affect more than half of all older adults, while also being established AD risk factors that have the potential to be modified. Understanding the mechanisms that impact trajectories of brain and cognitive aging is expected to lead to strategies that delay and prevent AD. PROJECT 2 - PUBLIC HEALTH RELEVANCE / NARRATIVE Recent years have seen an alarming increase in the number of Americans who are obese and insulin resistant, two risk factors for pathological aging and cognitive decline. Understanding the effects of metabolic risk factors on brain health in midlife will fill a critical gap in knowledge concerning pathological brain changes that could be prevented in a large sector of the American population. |Willette, Auriel A; Johnson, Sterling C; Birdsill, Alex C et al. (2015) Insulin resistance predicts brain amyloid deposition in late middle-aged adults. Alzheimers Dement 11:504-510.e1| |Joshi, Gururaj; Gan, Kok Ann; Johnson, Delinda A et al. (2015) Increased Alzheimer's disease-like pathology in the APP/ PS1?E9 mouse model lacking Nrf2 through modulation of autophagy. Neurobiol Aging 36:664-79| |Engelman, Corinne D; Koscik, Rebecca L; Jonaitis, Erin M et al. (2014) Investigation of triggering receptor expressed on myeloid cells 2 variant in the Wisconsin Registry for Alzheimer's Prevention. Neurobiol Aging 35:1252-4| |Kim, Hyunwoo J; Adluru, Nagesh; Bendlin, Barbara B et al. (2014) Canonical Correlation Analysis on Riemannian Manifolds and Its Applications. Comput Vis ECCV 8690:251-267| |Hoy, Andrew R; Koay, Cheng Guan; Kecskemeti, Steven R et al. (2014) Optimization of a free water elimination two-compartment model for diffusion tensor imaging. Neuroimage 103:323-33| |Okonkwo, Ozioma C; Oh, Jennifer M; Koscik, Rebecca et al. (2014) Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer's disease. J Int Neuropsychol Soc 20:422-33| |Mielke, Michelle M; Haughey, Norman J; Bandaru, Veera V R et al. (2014) Cerebrospinal fluid sphingolipids, ?-amyloid, and tau in adults at risk for Alzheimer's disease. Neurobiol Aging 35:2486-94| |Fischer, Barbara L; Gleason, Carey E; Gangnon, Ronald E et al. (2014) Declining cognition and falls: role of risky performance of everyday mobility activities. Phys Ther 94:355-62| |Johnson, Sterling C; Christian, Bradley T; Okonkwo, Ozioma C et al. (2014) Amyloid burden and neural function in people at risk for Alzheimer's Disease. Neurobiol Aging 35:576-84| |Okonkwo, Ozioma C; Schultz, Stephanie A; Oh, Jennifer M et al. (2014) Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology 83:1753-60| Showing the most recent 10 out of 46 publications

Lawrenceville Police Benevolent Fund endows GGC criminal justice scholarship The Lawrenceville Police Benevolent Fund (LPBF) has established an endowed scholarship for Georgia Gwinnett College students pursuing bachelor degrees in criminal justice. Representatives of the Lawrenceville Police Department (LPD) recently visited with GGC leaders to celebrate the completion of a $50,000 fundraising project to support the Lawrenceville Police Scholarship. “GGC is uniquely positioned to provide our future officers with a first-rate education,” said Captain Jeff Smith of the LPD. “We are very proud to establish the Lawrenceville Police Scholarship at Georgia Gwinnett. Together, the Lawrenceville Police Benevolent Fund and GGC will be able to ensure that Lawrenceville has one of the best prepared and best educated local police forces in the country.” Plans for the scholarship began in 2009, when LPD and GGC recognized that they shared a synergy. The college was in the process of introducing a criminal justice degree, while the LPD was renewing its emphasis on the importance of education to its employees. The two organizations began working together to establish a scholarship fund for criminal justice majors. Initial contributions for the scholarship fund came from the Lawrenceville Police Benevolent Fund’s highly successful event, “A Run to Remember,” which honored the heroes of 9/11/01 and drew hundreds of participants each year. The run evolved into a successful partnership with Rock ‘n Ribville, which led to completion of the endowment in three years. “We have been pleased to have the Lawrenceville Police Department’s support of our scholarship program from the very beginning,” said Lori Buckheister, associate vice president for Development at GGC. “With an endowed scholarship the funds raised remain in a managed account, and the account’s yearly interest is paid out as the scholarship. The benefit of endowments is that they provide permanent funding for their scholarships.” Due to the success of the LPBF’s fundraising efforts, the Lawrenceville Police Scholarship Fund will begin awarding scholarships to GGC students in fall 2014, ahead of its original schedule. “The close collaboration between GGC Police and the LPD has long been a valuable asset to Lawrenceville. Now, we are working together to support the future of our own law enforcement community,” said Randy Johnson, chief of the LPD. “The Lawrenceville Police Scholarship represents a concrete contribution to the safety and well-being of people living in Lawrenceville and Gwinnett County,” said Stas Preczewski, interim president. “We are grateful to the Lawrenceville Police Benevolent Fund for its tremendous effort in raising funds for this scholarship. Georgia Gwinnett College looks forward to honoring this commitment by educating some of the finest criminal justice graduates in the State of Georgia.” For more information about how to support the college, visit www.ggc.edu/give. # # #

It really is a case of what you are gaining. If you have not tried biwiring yet you arent missing anything. The effect of biwiring on your speakers in your system only has as much value as you place on it. I know a lot of people who did not like the result that came of biwiring their biwirable speakers-did not like having to run extra wire or the sound quality that resulted. I know a few people who own B&W speakers-as I do,who felt biwiring made their speaker sound over blown.I definately feel my speakers-B&W 602s2 and cdm1 nts, benefit from the additional wire. In both instances they sounded smoother and more detailed, as well as gaining a greater presence that was not apparent before. I am inclined to think it is a synergy issue. Biwiring aside, you first have to figure out what cable is going to work with your system. Then it might pay dividends to experiment. Also, Shorter is better, but I think it will pay to be realistic. Some speakers need space, and a longer run of speaker cable with offer a greater level of flexability. If your speakers are anywhere as placement sensitive as mine you will appreciate the extra length of cable.In the end, You may want to experiment with speaker placement and different cables before you make your purchase,and by then you will likely know whether you want to go the biwire route.

ROPEMAKER PLACE, LONDON Tuesday 01 Nov 2011 With its EMEA headquarters in London, the Macquarie Group expanded it’s operations and found themselves fragmented in different buildings. The new Ropemaker Place building offered the opportunity to consolidate their various businesses and 1,200 employees into one connected community. The typical segmentation that occurs in the stacking of multi-story office buildings presented an obstacle. In an effort to facilitate a clear and open connection between the corporate divisions, a new vertical opening in the form of an Atrium was carved out. Working between the existing structural steel bays, a six story organically shaped volume was created. Planned along the logical path of travel between different functions, a new continuous red staircase became the banner of connectivity, and is emphasized through its engagement with a large communal amenities floor and a guest relations/conference floor. Meeting pods, kitchen break out areas and communal spaces embellish the sides of the Atrium, bringing transparency and user interaction to the heart of Macquarie. The lowest two floors are devoted to Trading Rooms and their support functions, and form the base of the new organization, with client advisory businesses stacked above. Clients and visitors are directed to the top floor meeting areas and can interact with the businesses within the open Atrium volume. Through revealing its operations in this dramatic way, Macquarie has confidently introduced a much-needed transparency into the financial services market. Several sustainable initiatives are achieved, including significant decreases in energy consumption, waste and lift usage, and net carbon footprint reduction, in line with the top rated BREAAM building. The visible energy of people circulating and interacting in the transparent Atrium serves as the catalyst for drawing the different business units together and provides the synergy to collaborate with each other in new business ventures. The project was completed March 2011.

Quantum Blue - Sergey Galitskiy - Quantum of Solace - John Staluppi - Atlantic Auto Group - The yacht Quantum of Solace was built as Alfa III in 2001. She was acquired by Alexander Shnaider, founder of the Midland Group, who named her Midlandia. In 2008 she was purchased by John Staluppi who named her Quantum of Solace. He sold her again in 2011, and she is now named Elysium. US millionaire John Staluppi is the owner of the yacht Quantum of Solace. Staluppi is a successful car dealer and founder of the Atlantic Auto Group. Staluppi owns several other yachts all named Skyfall. See more hereunder. Portland Holdings - Queen K - Oleg Deripaska - Oleg Deripaska is the owner of the yacht Queen K. Deripaska is the CEO of Rusal, the largest aluminum company in the world. Rusal accounts for almost 9% of the world's primary aluminum output and 9% of the world’s aluminum production. In 2012 Rusal realized sales of $ 11 billion. Deripaska is one of the richest Russians, with an estimated net worth of US$ 4 billion. In 1998, Deripaska established Volnoe Delo, Russia's largest private charity foundation. The fund aims at developing education and science, preserving spiritual and cultural heritage, and improving standards in public health. Deripaska owns 25 percent of the Austrian construction company Strabag SE, owned by Hans- Quinta Essentia - Valentin Zavadnikov - Liquor: Synergy Group - The yacht Quinta Esstentia was built for Valentin Zavadnikov is shareholder of the Russian Synergy Group. Synergy is one of the leading and fastest- Abdullah al Futtaim - Al Futtaim Motors - Bill Duker - Built for Kenneth Rainin - Rainin Instrument Company (sold to Mettler Toledo) - Bill Duker is the owner of the yacht Rasselas. Rasselas was built for Kenneth Rainin, the founder of the Rainin Instrument Company. Initially Rainin distributed laboratory instruments and supplies. Later Rainin secured the rights to sell Pipetman, a line of laboratory pipettes, and through design improvements, built the Pipetman into the dominant brand of pipettes used in laboratories. In 2001 Mettler Toledo acquired Rainin Instrument Company for USD 290 million. Rainin’s yacht Rasselas was named after Samuel Johnson’s fictional character, The Prince of Abyssinia, who traveled throughout ancient Arabia in search of happiness. Kenneth Rainin passed away in 2007. The Kenneth Rainin Foundation is active in health, education and arts. Read more about Bill Duker hereunder at his sailing yacht Sybaris. Roberto Cavalli - Fashion Roberto Cavalli - Robert Cavalli Is an Italian Fashion designer. Roberto Cavalli has 130 sales points worldwide and realized a turnover of USD 200 million in 2010. The net worth of Roberto Cavalli is estimated at USD 500 million. Charles Butt - H.E. Butt - Charles Butt is the owner of the sailing yacht Rebecca. Charles Butt is the CEO of the grocery chain H.E. Butt, based in Texas. The company was founded in 1905 by Butt’s grandmother. Nowadays HEB is Texas’s largest privately held company, and the US’ 25th largest retailer. The company realizes annual sales of more than US$ 20 billion in 340 stores with 76,000 employees. The company donates 5% of the annual profits to charity. Charles Butt’ net worth is estimated at US$ 10.9 billion. His classic styled sailing yacht Rebecca was built at Pendennis Shipyard in 1999, to a German Frers design. The yacht frequently participates in regattas. Built as Boadicea for Reg Grundy - Reg Grundy Productions - Reg Grundy is an Australian media entrepreneur. He started as a radio sports commentator, and founded the production company Reg Grundy Organization in 1960. He produced successful shows as Sons and Daughters, Neighbours and The Restless Years. In 1995, he sold the Grundy Organization for USD 400 million to the media and publishing company Pearson PLC, now FremantleMedia. In 2008 the net worth of Reg Grundy was estimated at USD 850 million. Grundy named his yacht Boadicea after the queen of the Iceni Celts. Grundy sold the yacht Boadicea in 2009. The current owner of Reborn is French investor and politician Bernard Tapie. Tapie is famous for investing in the sports brand Adidas. In 1990 Bernard Tapie acquired 80% of Adidas for EUR 244 million, in 1991 he acquired an additional 15% for EUR 10 million. In 1992 he sold Adidas for approx. EUR 317 million to Credit Lyonnais. Tapie later claimed that he was swindled by Credit Lyonnais who resold the company to French investor Robert Louis Dreyfus for EUR 617 million. In a controversial court decision Tapie was awarded EUR 385 million in 2008. In 2013 French prosecutors charged Tapie with fraud in this case and seized assets worth several hundred million. It is unclear whether Tapie’s yacht Reborn was seized as well. Red Dragon - Baron Guy Ullens de Schooten Whettnall - Weight Watchers - Baron Guy Ullens de Schooten is the owner of the sailing yacht Red Dragon. He is heir to the Wittouck family fortune. The Wittouck family was owner of the Tiense Suikerraffinaderij, Belgium’s largest sugar producer. In 1989 the Tiense Suikerraffinadery was sold to the German company Südzucker for approx. EUR 950 million. Since then Baron Guy Ullens de Schooten and his family member Erik Wittouck founded Artal, a private investment vehicle based in Luxembourg. Artal’s investments include Eurobake, Europe's largest baking company, Pizza Hut Finance, operating more than 100 restaurants and Neuhaus, a chocolate manufacturer. Artal’s most successful investment is Weight Watchers, which was purchased from Heinz for USD 735 million in 1999 and which was floated on the NYSE stock market in 2001 with a USD 400 million profit. In 2007 Artal received another USD 540 million for shares Artal still owned in Weight Watchers. And in 2010 and 2011 Artal sold another 12 million shares for more than USD 1 billion. Baron Ullens de Schooten is an active philanthropist, donating to good causes through his Guy and Myriam Ullens Foundation. He is a leading art collector, who founded the Ullens Centre for Contemporary Art, based in Beijing it is the first private non- Reef Chief - James Dicke - Crown Equipment - James Dicke is the owner of the yacht Reef Chief. Mr. Dicke is CEO of Crown Equipment Corporation. Crown Equipment designs, manufactures, distributes, services and supports material handling products. Crown was founded in 1940 as a small one- Sheikh Ahmed Bin Rashid Al Maktoum - Sheikh Ahmed Bin Rashid Al Maktoum is the owner of the yacht Reem. Sheikh Ahmed is a brother of the Emir of Dubai Sheikh Mohammed bin Rashid Al Maktoum. Sheikh Ahmed is President of the Al Wasl Sports Club which one of the most successful sports clubs in the UAE. He is also active in Thoroughbred horse racing through the Godolpin Stables and is considered to be one of the biggest horse owners in the world. The yacht Reem was built at Trinity Yachts and delivered in 2013. The yacht features a total of 9 guest cabins. Dogukan Boyaci - Pruva Yachting - Dogukan Boyaci is the owner of the yacht Regina. The Boyaci family actually owns the Pruva Yachting company, builder of the yacht Regina. SuperYachtFan tried to find more information about the Boyaci family, but due to a lack of fluency in the Turkish language, was not able to find more information. Do you know more about the Boyaci family? Please do sent us a message. The sailing yacht Regina was featured as Chimera in the James Bond movie Skyfall. Regina is available for charter. Regina d'Italia - Stefano Gabbana - Dolce & Gabbana - Stefano Gabbana is the owner of the yacht Regina d’Italia. Gabbana founded the Italina fashion house Dolce and Gabbana together with Domenico Dolce. Established in 1985, today Dolce&Gabbana is one of the leading international groups in the fashion and luxury goods sector. The D&G Group designs, produces and distributes high- Jamie Coulter - Lone Star restaurant chain lonestarsteakhouse.com Jamie B. Coulter is the owner of the yacht Relentless. Coulter is Chairman and CEO of Coulter Enterprises, Inc., a private investment firm. He was founder of Lone Star Steakhouse & Saloon, Inc. In 2006 he sold the company for more than USD 100 million to a private equity investor. Lone Star operated more than 200 restaurants. Remember When - John Rosatti - Plaza Auto Group - John Rosatti the oner of the yacht Remember When. Rosatti is the founder of the Plaza Auto Mall in Brooklyn New York. Plaza Auto Mall was awarded as a Top 100 dealership by Wards Automotive. Plaza Auto Mall carried more than 15 different car brands. After his wife Bonni lost her life he sold a large part of the Plaza Auto Mall and moved to Florida with his children. Together with his close friend John Staluppi he founded Millenium Superyachts. Rosatti also set his focus on creating a restaurant franchise concept that has now become the fastest- Alexandr Tkachev - Governor of Krasnodar Krai - Alexandr Tkachev was the owner of the yacht Renegade. Tkachev is the Governor of Krasnodar, a federal subject of Russia. He is the owner of a large company named Agricultural Complex, which was founded by his father. Agrocomplex is Russia’s largest agricultural company, active in growing of crops, dairy products, meats, poultry, and bakery. Agrocomplex has 16,000 employees and 200,000 hectares of land. The yacht Renegade was sold and is now named Robusto. David V. Johnson - Real estate, Victor International Corp. - David V. Johnson is the owner of the yacht Resolute. David Johnson is the founder of the Victor International Corporation. Victor International is a U.S. real estate and resort developer. The company has created more than 40 developments, including Bay Harbor, Michigan, a USD 1 billion, 1,200 acre luxury resort community, Turtle Lake, a USD 400 million private community in Bloomfield Hills, Michigan and Oil Nut Bay. Oil Nut Bay is an island paradise resort community that features 88 home sites on 300 acres (121.4 hectares). David Johnson is active in philanthropy. In 1988, Johnson established The Victor Foundation, providing charitable contributions to foster programs for children, the physically challenged and young adults. Peter Sperling - Apollo Group - Peter Sperling is the owner of the yacht Reverie. Peter Sperling is the son of John Sperling, who founded the for- Roy E Carroll - The Carroll Companies - Richmond Lady - Don Davis - Richmond Yachts - Don Davis is the owner of the yacht Richmond Lady. In fact Ron Davis owns the Richmond boatyard itself. Davis is a successful restaurant entrepreneur, he owns the Great Texas Food Corporation which operates several restaurants, including the Ralph & Kacoo's restaurant chain, Cafe Del Rio, Brazos Cattle Company and the Cattle Company of Texas. Don Davis acquired the boat yard when the company ran into financial troubles, while building Davis’ yacht Cloud Nine, later named Penny Mae. Rising Sun - David Geffen - Geffen Records - Rising Sun is owned by David Geffen, founder of Geffen Records. RL Noor - Tarek Nour - Tarek Nour Communications - Tarek Nour is the owner of the yacht RL Noor. Tarek Nour is the CEO and shareholder of Tarek Nour Communications. Tarek Nour Communications (TNC) is Egypt's largest communications services groups. The group is active advertising, media, consultancy, Branding and PR Marketing. TNC was founded by Tarek Nour in 1976 when he started the first Egyptian advertisement agency. The group now includes the Egypt TV channel Al Kahera Wal Nas. Nour ‘s yacht RL Noor is built in Turkey by Bilgin Yachts. The yacht RL Noor is built out of mahogany, in Turkish wood building tradition. Jimmy John Liautaud - Jimmy John's Gourmet Sandwiches - Russ Weiner - Rockstar Energy - Russ Weiner is the owner of the motor yacht Rockstar. Weiner is the founder of Rockstar Energy, a leading energy drink brand in the US. In 2013 Rockstar was the 3rd largest energy drink in the US, with sales of more than US 800 million. Russ Weiner’s father is Michael Savage, the US radio host. Forbes estimates the net worth of Russ Weiner at USD 2.5 billion. The yacht Rockstar was built as Blind Date for investor Peter Hochfelder, founder of Brahman Capital. Victor Vargas - Banco Occidental de Descuento - Victor Vargas is the owner of the superyacht Ronin. Victor Vargas is the owner of Banco Occidental de Descuento, the fifth largest bank in Venezuela. As young man Vargas married into the one of Venezuela’s elite banking families: the Cisneros family. Vargas later became one of the country’s smartest en most successful bankers. In a Wall Street Journal interview Vargas said that he owns two yachts, three planes and six houses. Victor Vargas’ other yacht is the 2001 Feadship Sea Racer. Vargas purchased Ronin from Larry Ellison. Royal Romance – motor yacht – 92.5m (303ft) - Viktor Medvedchuk – net worth USD 460 million – Ukraine Rupert Murdoch - News Corporation - Rupert Murdoch is the owner of Rosehearty and Vertigo. Jeroen Piqueur - Optima Bank - Jeroen Piqueur is the owner of the superyacht Rubeccan. Piqueur is the founder of the Belgium based Optima Bank. Optima started in 1991 as a Financial Planning adviser and in a few years became market leader in Belgium. In 2011 Optima received a bank licence with the acquisition of the Ethias Bank. Optiver is the publisher of the financial magazine Capital Magazine. Jeroen Piqueur named his yacht Rubeccan after his two children: Ruben and Rebecca. Jeroen’s son Ruben Piqueur is the CEO of the real estate developer Optima Global Estate. Anthony Bakker - Anthony Bakker is the founder of Blackbaud Inc., a supplier of software and services specifically designed for nonprofit organizations. The company was founded in 1981, and now employs over 2,100 people. In 1999 Anthony Bakker sold a 60% stake for USD 155 million to San Francisco- Greg Meyer - Greg Meyer is the owner of the yacht Sahana. Meyer founded the Rental Management Group, active in the lease of office equipment, doing the finance for corporations such as Motorola, NEC, Toshiba and Panasonic. Meyer sold the company in 2004 to finance group Allco. In 2005 he founded EPAC Salary Solutions, providing novated car leases and salary packaging solutions. In 2011 Meyer sold APAC to RACV for AUS$ 23.7 million. Meyer is now active in real estate development, he owns the BASK Gili Meno Resort. His yacht Sahana was built in 2008 as Eendracht for Austal founder John Rothwell. She is available for charter. Saint Nicolas - Vassily Anisimov - Rossiyskiy Kredit Bank - Vasily Anisimov is the owner of the yacht Saint Nicolas. Anisimov founded the Coalco company in 1999. The Coalco company acquired shares in aluminum plants, mines, and factories. Vasily Anisimov was also co- Mohamed al Fayed - Hotel Ritz Paris - Mohamed al Fayed is the owner of the sailing yacht Sakara. Mohamed al Fayed is a succesfull businessman born in Egypt. He is known a s the owner of the Ritz Hotel in Paris and as the former owner of the Harrods Department Store in London. He sold Harrods in 2010 for USD 1.5 billion. His son Dodi al Fayed died in a car crash in Paris along with Diana, Princess of Wales. AL Fayed also owned the motor yacht Sokar, which he sold in 2014. Salperton IV - Barry Houghton - Barry Houghton is the owner of the yacht Salperton. Houghton is founder of Rainford, a mechanical and electromechanical components manufacturer. Rainford was sold to Reltec, a US electronics company for USD 134 million in 1996. Reltec itself was later sold to the Marconi Group, which collapsed in 2005. Barry Houghton named his sailing yacht Salperton after the village of Salperton in Gloucestershire (UK) where he owns a large estate. John Groenewoud - real estate - John Groenewoud is the owner of the yacht Salute. Groenewoud is a Dutch real estate developer. He and his family are the owners of the Groenewoud Vastgoed Group (Groenewoud Real estate group) now known as Built to Build. The Dutch magazine Quote estimates Groenewoud’s net worth at EUR 110 million or approx. USD 150 million. Groenewoud purchased the yacht Salute from Dutch retailer Eric Albada Jelgersma while the yacht was still in built at Perini Navi. Eric Albada Jelgersma became paralyzed after an 2005 injury on this 52 meter yacht Liberty II also built by Perini Navi. More Yacht Owners? Download the Full SuperYacht Owners Register for US$ 50

go 151 with severne sail i am a new windsurfer bought go 151, but beginner, i bought it with synergy 5.4 rig to start up. The question is since i would like to advance and try to plan can i use it with a 6.5 camber severne overdrive? or is something that no one will recommend. Thanks in advance.

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No LeBron James, no Dwyane Wade, no problem for the Miami Heat—at least so far. The defending NBA champions head into their Saturday evening clash with the Philadelphia 76ers at AmericanAirlines Arena possibly more confident than they've ever been. Following the end of the Heat's historic 27-game winning streak, they seem to have done an understandable thing: hit the pause button. James and Wade have missed each of the team's past three games with leg injuries and have been joined with a rotating cast of secondary characters, including Ray Allen and Mario Chalmers. With only Chris Bosh as the constant, Miami has somehow continued winning. The Heat took down the San Antonio Spurs last Sunday and the Charlotte Bobcats on Friday, losing only to the New York Knicks in a game Carmelo Anthony scored 50 points. Those victories have kept Miami in a firm lead for home-court advantage throughout the NBA playoffs—the only thing this Heat team has left to accomplish. While it's uncertain if Wade and/or James will return to the lineup on Saturday, the 76ers will look to make their return—or non-return—a living nightmare. Philadelphia has had a disappointing season from start to finish—spurred most prominently by Andrew Bynum's season-long absence—but has battled to a 6-4 record in its last 10 games. The Sixers are still mathematically eligible for the playoffs, but only in the sense you or I are "eligible" bachelors for Kate Upton. It isn't happening. That means all Doug Collins' squad has left is moral victories—like taking down the defending champs on their home floor. With that in mind, here is a complete breakdown of everything you need to know about Saturday night's clash. Start Time: Saturday, April 6 at 7:30 p.m. ET Location: AmericanAirlines Arena in Miami Team Records: Philadelphia 76ers (31-44), Miami Heat (59-16) TV Info: ESPN Live Stream: Watch ESPN 76ers Injury Report (Via CBS Sports) G Dorrell Wright, Elbow, Questionable C Andrew Bynum, Knee, Out for Season G Jason Richardson, Knee, Out for Season Heat Injury Report (Via CBS Sports) G Ray Allen, Ankle, Questionable G Dwyane Wade, Ankle, Questionable F LeBron James, Hamstring, Questionable Key Storyline: Will Wade and LeBron Finally Return to the Lineup? Poor Chris Bosh. He's the largely forgotten member of the Heat's Big Three. A guy who does more for the team than anyone will ever give him credit for—and he doesn't even get to join the Bench Friends Club on the "injury" report. Friday's game against the Bobcats marked three straight that LeBron James and Dwyane Wade have sat out due to injury, the former a hamstring and the latter an ankle ailment. The Heat are surprisingly 2-1 without Wade and James during this stretch. Their offense has imploded, scoring less than 90 points per night, but the Heat have played strong defense—particularly Sunday against San Antonio. It's been encouraging for Miami and troubling for the rest of the league that a roster that resembles Bosh's Toronto days can still compete on a nightly basis. Will you watch this game if LeBron James and Dwyane Wade don't play? Their 2-1 record also isn't going to make the Heat be in any hurry to bring James and Wade back—and understandably so. Miami has long locked up the No. 1 seed in the Eastern Conference and has a four-game lead in the loss column over Oklahoma City and San Antonio for home-court advantage in the NBA Finals should they get there. So why not get your two best players some rest, even if they're technically still healthy enough to be on the floor? It's a sound strategy. The Heat still have to make sure they don't keep their stars parked for too long, though, and Saturday is as good of time as any to bring them back. Miami is on national television for the second consecutive night, so the suits at ESPN are undoubtedly hoping that's the case. Friday saw a LeBron-and-Wade-less Heat square off against a Charlotte team with the NBA's worst record. Not exactly appointment television. And the Sixers' descent from preseason playoff favorite to lottery dweller doesn't make them all that intriguing by themselves either. Without James and Wade, the interest in this game from a mainstream level is going to hit the doldrums. This game will either mark the return of two of the five best basketball players in basketball...or it's not. That's really all this comes down to. X-Factor: Heat Transition Offense This will come as no surprise, but the Heat are a dreadful offensive club without Wade and James. They have scored no higher than 90 points in any of the past three games and have scored below their season 1.02 points per possession average in every game—including a paltry 0.92 Friday night versus Charlotte, per Synergy Sports. No duh. Of course Miami is worse offensively without two of the best offensive forces in the league. But what's notable and what will be key to Saturday night's contest is how the Heat's offense has changed without James and Wade leading the attack. By far the most notable switch has come in transition. According to Synergy Sports, the Heat have used 13.4 percent of their possessions—meaning where "used" means a possession ending in a field-goal attempt, turnover or free-throw attempts—in transition. They are unsurprisingly ascendant in the open court, scoring a league-best 1.22 points per possession. In the three games without Wade and James, Miami has been dreadful. The Heat are still using 10.8 percent of their possessions in transition, per Synergy Sports, but their effectiveness has cratered. They've created just 19 points in transition over the past three games, good for an appalling 0.61 points per possession. That's half of their season-long rate and would be the worst in the NBA by a country mile. Here is a little sampling of what Miami looks like in transition without its two stars. It's clear from the second Allen touches the ball that he doesn't want to be handling it. He's instantly looking for a ball-handler, likely Norris Cole, but Cole is already sprinting his way down the floor with no intention of bringing the ball up. So, instead, 37-year-old Allen comes barreling into the middle of San Antonio's defense and throws up a garish shot that goes off the rim. Instead, what Allen is initially looking to do on this play is what he has all season—sprint right to the half-court line, begin slowing his stride and setting up for an in-rhythm three-pointer from either the left corner or from either wing spot. Again, much of whether the Heat are able to be effective in transition Saturday comes down to the status of Wade and James. The Sixers have been strong defensively in transition sets all season, ranking seventh at 1.1 points per possession, but Miami has torched Philadelphia in the open court this season to the tune of a 16-of-23 shooting performance, per Synergy. Miami has cratered points over the past three games due to its lack of transition opportunities. If Wade and James stay out of the lineup, the Sixers may well win simply by getting to 91 points. Key Matchup: Evan Turner vs. Miami's Isolation Defense There's just one problem with the 91-point theory for Philly: The Sixers struggle to get there themselves. One of the worst and least-inventive clubs in the league, coach Doug Collins has taken a fair share of understandable criticism about the team's wretched offensive performance. All it takes is a quick look at the stat sheet to see why the Sixers struggle so badly. They rank in the bottom 10 in shots taken in the restricted area and no team in the league takes more mid-range jumpers—the most inefficient shot in basketball. When breaking it down into individual plays, Philadelphia is good at two things—posting up and isolation. Miami is a top-half team defensively in post-up situations, so the Sixers aren't going to be having any luck with that on Saturday even without Wade and James—sorry Spencer Hawes. That being said, the Sixers could have a ton of success running isolation plays against Miami. According to Synergy Sports, the Heat are the second-worst isolation team in the NBA, giving up 0.89 points per possession. That contrasts with Philadelphia's ninth-place ranking on the offensive end, where it scores 0.84 points per possession. (Miami is the league's best ISO team offensively.) The titular figures in the Sixers' isolation sets are (unsurprisingly) Jrue Holiday and Evan Turner. Two ball-dominant, dribble-heavy players, Turner and Holiday are responsible for about 63 percent of the Sixers' isolation finishes this season, per Synergy. While it's Holiday who uses a lion's share of the possessions—37.25 percent to be exact—it's Turner who is more effective. The third-year forward is averaging 0.92 points per possession, which is right around Miami's league-best rate overall. The reason Turner is so effective is his mid-range game. Turner came out of Ohio State breaking down people off the dribble and knocking down mid-range jumpers. That remains arguably his best feature in the NBA and will be critical for Philadelphia against Miami. Projected Starting Lineups PG: Jrue Holiday SG: Damien Wilkins SF: Evan Turner PF: Thaddeus Young C: Spencer Hawes PG: Mario Chalmers SG: Dwyane Wade/Ray Allen/Mike Miller SF: LeBron James/Rashard Lewis PF: Udonis Haslem C: Chris Bosh It's nearly impossible to pick a game when you don't know whether the contest's two best players are going to be in the lineup. So let's just work with what know—that Wade and James have missed the last three games—and assume the same for Saturday. As such, don't be expecting too much scoring when you tune into ESPN. The Heat have struggled to make real headway on that end as we covered, and the Sixers' dreadful offense isn't going to spring to life overnight—even with Turner taking on Miami's isolation defense. Bosh will likely see a ton of Thaddeus Young defensively, which also puts the Heat at a competitive disadvantage. Sixers win this game by sheer virtue of having all of their players, and the fact that Miami has to fold without the world's best player eventually. Score Prediction: Philadelphia 76ers 91, Miami Heat 88

Designer Trina Turk is inspired by the Golden State's multicultural mix, creativity, craftsmanship, architecture, and landscape--a synergy that permeates her contemporary, colorful aesthetic in home decor and fashion alike. Infused with bold signature prints and dynamic hues unique to each collection, her modern and optimistic creations meld the best of classic American design with a California confidence. 1830s French Louis Philippe large-scale giltwood mirror with gently rounded corners and beaded detail. A very early example with wood back and frame retaining the wooden nails used in early 19th century construction. Some loss to gesso with multiple layers ... Large-scale Regency-style overmantel mirror with Corinthian column side pilasters featuring carved capitals and fluted bases. The surface is painted in an antiqued sage green finish with gilded accents. Minimal age wear. French Louis XVI-style gilt mirror, circa 1900. Solid wood frame finished in a gold color, heavily carved with flowers, roses, scrolls, vases, leafs, and seashells. Fully reflective. Minor wear. Please note: It has two mirrors that join in the center ...

toronto,31st August-2014,(IANS): Older adults who stay active by volunteering are likely to receive a health… Mumbai(instahealthsolutions): Over the years the healthcare industry has seen progress in patient engagement facilities. The medical fraternity now believe that patient engagement is the most effective treatment the healthcare industry can provide today. The topic has created a buzz in the field of medicine. Many members of the medical community claim that patient management is the future of healthcare; but what exactly is patient engagement? We’ve all come across the term of customer engagement in the field of business, retail and so on. Patient engagement in the field of healthcare goes along the same lines. Engaging patients by utilizing better technology in Hospital Management Information System, initiates communication between the physician and the patient. This way the patient can learn about the ailments and the mode of treatment. These interactions lead to better informed patients and this enhances personal care. Physicians claim that patients respond better to treatment due to this synergy. This transparency has elevated the trust quotient among patients.They can now access their medical history, reports and their treatment details online. Hospital management systems that are linked to online portals for the convenience of patients are on the rise. Today, nearly everyone is pretty tech savvy. Therefore, new and better technology is being adopted by the healthcare industry. What are the advantages of patient engagement? With improved patient engagement facilities in the field of medicine, costs are cut down. The amount of paperwork required is reduced and with the healthcare going digital, errors can be reduced or eliminated. Scheduling appointments and payment methods all of these can be done cost effectively. Patient satisfaction is ensured. Patients find it very convenient to take care of all their medical needs online without really having to be physically present. With wearable fitness monitoring devices, doctors can monitor their patient’s vital statistics from any remote location. Ease in communication and further better health information management systems can help identify health patterns and prevent epidemic patterns. Do you want to ensure the best services for your patients in your healthcare facility? Insta Health solutions can help you enhance your patient engagement with their state-of-the-art hospital information systems. Better to know more, visit www.instahealthsolutions.com

Dashboard Series: Simple Content Marketing Calendar Mind Map The new year is almost here, so it’s time to start chalking up those resolutions. We can’t help you get to the gym more, but we can help you use MindManager to make your content marketing process more productive and efficient. You can get started with this Simple Marketing Editorial Calendar and start using it as a scalable dashboard for planning, scheduling, and tracking your content marketing. Eliminating Content Chaos Recent content marketing research conducted by the Content Marketing Institute shows that most content marketing programs suffer from a lack of direction and focus. A disorganized content marketing strategy is associated with a lack of confidence and satisfaction in content marketing efforts. This Simple Content Marketing Editorial Calendar provides a straightforward, scalable framework for you to replace chaos with certainty in your content marketing program. Here’s how it works: Replace chaos with synergy. Use the Simple Editorial Calendar to get a big picture view of your marketing. It helps you simplify content planning, maximize the quality of individual projects, and boost content productivity by re-purposing previously-addressed topics. Promote team-based content production. Identifying monthly themes and upcoming content needs in advance will boost efficiency and simplifies delegation—especially important when content creation involves a partnership between writing, design, and IT. Extend the life of your content. Use existing content as the building blocks of future projects. More and more published books and profitable video projects originate as blog posts. In a recent interview, when I asked David Meerman Scott how he could be substantially rewrite his New Rules of Marketing and PR every two years, he responded, “I’m always blogging.” The heart of the Simple Editorial Calendar is to select a theme for each month as far ahead of time as possible, and using the monthly themes as a framework for the majority of your content around that topic. Understanding the difference between themes and topics is the key to planning and implementing a better content marketing program. Although topics and themes are terms that are often used interchangeably, there are significant differences between them: Themes describe broad categories, or groups, of topics. Themes save you time by eliminating decisions and jumpstart your content marketing by providing a structure for deciding what to write about each week Topics refer to ideas and titles describing specific articles, blog posts, newsletters, podcasts, or videos. A topic typically addresses a specific approach, breakthrough, challenge, example, solution, or trend. Take it to the Next Level The next step is to break each project into the tasks needed to complete it, and use MindManager’s Resources feature to assign responsibility and Start Dates and Due Dates for each task. The tasks associated with blog posts, for example, require: - Choosing the title and preparing the first draft. - Reviewing the title and tweaking its search engine appeal. - Creating graphics to appear at top of the blog posts, as well as within each post. - Additional graphics must also be sized and formatted social media promotional use. - Revising and editing the first draft from a fresh perspective. - Posting the blog post. Turn the Editorial Calendar Into a Content Dashboard From this simple start, you can build additional features into your editorial calendar. You’ll be surprised at how much detail you can include without losing sight of the 12 content themes that will bind your content together. The more you explore the resources built into MindManager, the more you’ll grow to depend on your Simple Editorial Calendar as the hub of your content marketing. Download the template today and see for yourself!

A poignant book, tenderly written June 3, 2005 7:17 PM Subscribe Why's (Poignant) Guide to Ruby So you’ve got to know that synergy doesn’t actually mean synergy in this book. I can’t do normal synergy. No, in this book, synergy means cartoon foxes. What I’m saying is: this book will be starting off with an exorbitant amount of cartoon foxes. And I will be counting on you to turn them into synergy. Possibly the funniest computer programming book ever written. This thread has been archived and is closed to new comments

DETROIT — Mayoral candidate Benny Napoleon will soon be unveiling what he's called the "boldest neighborhood growth strategy that a mayoral candidate has ever presented." The announcement of his economic plan is scheuled for 6 p.m. Monday at Peace and Good Will Missionary Baptist Church at 20500 Moross in Detroit. The plan "creates three major developments in each sector of the city offering families a place to shop, eat and entertain; and ensures that Detroiters get the jobs to build and work at these establishments," Wayne County Sheriff Benny Napoleon wrote on his Instagram page Sunday. And on twitter Napoleon wrote: "We will build new public safety centers in every sector of our community for police/fire/ems to replace the crumbling buildings." Napoleon in August released his One Square Mile public safety initiative to place a community police officer in each of Detroit's more than 135 square miles. He said they would be the primary contact for residents not needing emergency assistance and would provide a direct link to the mayors office create synergy with other quality of life issues, like code enforcement, that are outside the Detroit Police Department's realm. A Detroit Free Press/WXYZ poll of 400 likely voters in the Nov. 5 general election, if accurate, revealed Napoleon has a long way to go if he wants to take the job from frontrunner Mike Duggan, former chief executive officer of the Detroit Medical Center. The poll, with a 4.9 percent margin of error, showed Duggan with a 2-1 lead, 49 percent to 25 percent. About 26 percent were undecided.

3 Simple Questions That Can Derail Your Reputation I think our businesses have synergy--maybe we could discuss over lunch? Asking for help is a good thing, but … there are times when reaching out can make you sound like an askhole. Yes, an askhole: a person who doesn't respect the value of other people's time, relationships or expertise. Askholes are takers--and they don't even realize (or care) that they're doing it. Before you open your mouth, consider the ways three common questions can derail your rep. Can I buy you a drink? When you ask someone to join you for coffee, drinks or a meal on the pretense of business, it's a pretty big request. It might seem a small favor--an hour or so of someone's time (and hey, you're buying!)--but here's what you're really asking: Would you take an hour away from cultivating your business to help me with mine? You're asking them to take time from their office, clients or projects. How to avoid being an askhole: Be clear with your expectations upfront. When making the initial request, state that you'd like to discuss X, Y and Z, and promise to take up no more than 30 minutes of their time. After the meeting, send your contact a $10 gift card to their favorite local coffeehouse as a thank you. Can you introduce me to …? Social media has made it pretty easy to see who's connected to whom. However, just because someone you know has a connection you need doesn't mean that you've earned the right to an introduction. An introduction is an even bigger deal than a drink or a meal--you're asking someone to trust you with a relationship they've cultivated and nurtured. How to avoid being an askhole: When you ask for an introduction, you obviously have an agenda. So make this type of request only from certain people in your network: those with whom you've already built a strong, reciprocal relationship. This way, they can refer you with gusto and can trust that you won't make them look like a jerk. Can I pick your brain? This may seem like a small request, but what you're asking for, really, is access to years of incredible successes, glorious failures and lessons learned--all for your benefit. You say "pick your brain"; they hear "unpaid consulting session." Unless you have a history of asking too much, your colleagues or mentor probably won't mind. But it's a pretty hefty request to throw at somebody you don't know very well. After all, would you ask your attorney for a quickie legal briefing in exchange for little more than a coffee? How to avoid being an askhole: If you want access to someone's how, you should be prepared to pay. Drinks and meals aren't fair pay for consulting. Anyone who is worth your request charges for their expertise and experience--and they can't pay for mortgages and college tuitions with lattes or martinis. Odds are you've made one or more of these askhole-type moves. We all have. What we need to do, however, is think about what it would feel like to be on the other end of the seemingly simple ask. This way, we can avoid becoming that guy who oversteps bounds and, instead, be that guy who's known as somebody who respects everyone's time and value. Not a bad rep to have.

24th September 1961: the Salone del Mobile makes its first appearance in Milan, brainchild of a small group of furniture makers, representative of the Federlegno trade organisation (now FederlegnoArredo), and organised by Cosmit for the promotion of exports of Italian furniture and furnishing accessories. Saturation of internal demand in the wake of the post-War reconstructions suggests exports as a possible outlet, but the small Italian manufacturers are in no position to tackle this on their own. A trade fair that would attract foreign interest seemed a viable opportunity. At the time there was still Mariano Comense’s standard-setting furniture Biennial, the selective Cantù Furniture Exhibition, the Pesaro Furniture Fair and the Permanent Exhibition of the Veneto Furniture Manufacturers’ Consortium in Padua, but these were all on very much a local scale. Milan, the financial capital of Italy, was identified as the most suitable location, and it had been playing host to the La Campionaria Fair since 1920. A Northern Italian delegation from the Italian Federation of Wood and Cork Industries, spearheaded by Tito Armellini approaches the 13 leading Italian furniture companies of the time, and thus the Italian Furniture Fair Promotion Committee is set up: Michele Barovero, Alessandro Besana, Franco Cassina, Piero Dal Vera, Vittorio Dassi, Angelo De Baggis, Mario Dosi, Aldo Falcioni, Angelo Marelli, Angelo Molteni, Silvano Montina, Mario Roncoroni and Vittorio Villa. The official press launch is held on 25th February 1961. The Promoting Committee has, in the meantime, appointed Alessandro Colli, then President of the Federation, as its Chairman. On 24th September that same year, the first edition of the Salone is launched in Pavilions 28 and 34 at the old La Campionaria Fair. The Salone del Mobile soon became synonymous with enduring success and assurance, a global benchmark for the Home Furnishing Sector. An invaluable tool for the industry as well as an on-going, quite extraordinary promotional vehicle. 1965 marked a year of change: the leading furniture sector companies such as Anonima Castelli, Arflex, Bernini, Boffi, Cantieri Carugati, Cassina, Cinova, Elam, Kartell, Mim, Molteni (just beginning to venture into modern furniture), Pierantonio Bonacina, Poltrona Frau, Poltronova, Rossi di Albizzate, Saporiti, Sormani, Stildomus and Tecno, are all featured together in Pavilion 30/3, creating a uniform commercial exhibition space, thanks to the forward thinking of Manlio Armellini, who takes over from his father Tito as Secretary General in 1974, and later as CEO until 2009. 1965 is also the year in which exhibitors begin to bring a great deal of attention to bear on the installations and Domus devotes its leader to the Salone. It is also the year in which the first Salone collateral event is held – a retrospective exhibition documenting furniture design in Italy. The Fair really takes off during the first 4 years, both in terms of visitor numbers and in terms of participation from Italian and foreign operators, achieving an immediate commercial response, establishing it not just as an observatory and showcase for the sector but also and especially as a driving force. Exports shoot up from 5,837,000,000 Lire in 1960 to almost 16,000,000,000 in 1964. 1967 and 1968 are boom time for the Salone, because of greater public interest and a burgeoning sense of homepride. Meanwhile, companies are busily engaged in technological research, especially in the fields of application of new materials. The Salone del Mobile very quickly proves to be an ideal marketing tool for what is a fairly pulverised sector (over 13 thousand firms with 205 thousand employees; a national distribution system hinging on 20 thousand outlets) with no other tools through which to channel its own overall potential. The figures speak for themselves: from 328 exhibitors occupying 11,860 square metres in 1961 to 2,720 at the 2011 edition, ranged over 210,500 square metres. Visitor numbers rise from an initial 12,100 to over 300,000 last year. Dizzying heights that have seen the Salone del Mobile become the undisputed showcase for the furnishing world. The Salone del Mobile, goes “international” in 1967 (only events that are assured of a substantial number of visitors, on top of the quality of their exhibits are allowed to style themselves “international”), and over the years another 6 exhibitions become strategically attached to it, extending and enhancing the specialist nature of the goods already on exhibit at the Salone itself, under the FederlegnoArredo system umbrella. 1974 marks the launch of Eurocucina, followed in 1976 by Euroluce, the former being the biennial International Kitchen Furniture Exhibition and the latter the biennial International Lighting Exhibition, which alternate in odd and even years respectively, forums where ideas, design, technology and innovation meet. EIMU, the exhibition devoted to the workspace is launched in 1982, renamed SaloneUfficio, the International Biennial Workspace Exhibition, in 2008. From this year on, Euroluce and SaloneUfficio are to be strategically located opposite each other, which will maximise the range of goods on offer, especially in the design and contract sectors, and respond to the steadily growing affinity between the worlds of work and lighting. The International Furnishing Accessories Exhibition is launched in 1989, rounding off the exhibitions devoted to domestic furnishing. Then in 1998, SaloneSatellite, the acclaimed launchpad for young creative talent and a benchmark for companies scouting for the trendsetters of the future, joins he ranks of exhibitions. Last but not least, in 2006 – the year in which the Salone leaves the old Fiera Campionaria exhibition centre (now known as Fiera Milano City) to move to the cutting edge Milan Fairgrounds at Rho, designed by Massimiliano Fuksas, the Salone Internazionale del Bagno (the International Bathroom Exhibition) makes its propitious debut on a biennial basis. It is now held in even years in tandem with EuroCucina, thus activating a total synergy in the sphere of technical issues and product development. The “Salone del Mobile.Milano” – is the umbrella name for all these events – therefore constitute a specialist yet heterogeneous trade fair, symbolising an all-encompassing way of working and interpreting modern industry. It is an exhibition system in its own right, in which large and small companies showcase their latest products, and it also provides an exceptional communication opportunity for all those operating within the sector. A single philosophy shared by organisers, exhibitors and visitors alike. The growth and success of the Salone, unlike many other international trade fairs, is bucking the trend as its waiting list continues to grow and its range of showcased goods continues to expand, in particular. The internationalisation process that first took the Milan Salone to New York and Moscow in 2005 with the Saloni WorldWide and in 2016 to Shanghai. In addition to the commercial fair, the Salone has featured collateral events, an international platform enjoying the “privilege of actuality,” that take stock of the state of art and the culture of design. The story begins in 1965, when – to underscore the presence of the new 30/3 Pavilion devoted to the most cutting edge design companies, which has proven one of the aces in the pack of the strictly trade event – the “Retrospective Exhibition on Furniture Design in Italy from 1945 to the Present” is held. A great many exhibitions since then have attempted to relate the genesis of the Italian productive identity and highlight its various aspects, telling the history of the great design Masters, or exploring the cross-cutting ties between marriages of design, art, fashion and food.

the underappreciated role of muscle in health and disease body fat distribution and risk of type diabetes in the general population: are there differences between men and women? the monica/kora augsburg cohort study long-term follow-up of cardiovascular disease risk factors in children after an obesity intervention effect of varying the ratio of nc to nc fatty acids by increasing the dietary intake of -linolenic acid eicosapentaenoic and docosahexaenoic acid or both on fibrino.. energy balance and the accuracy of reported energy intake in preadolescent children with cystic fibrosis effect of acute dietary standardization on the urinary plasma and salivary metabolomic profiles of healthy humans effects of nc fatty acids in subjects with type diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation an extract of black green and mulberry teas causes malabsorption of carbohydrate but not of triacylglycerol in healthy volunteers higher fasting plasma concentrations of glucagon-like peptide are associated with higher resting energy expenditure and fat oxidation rates in humans effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans effects of antiplatelet components of tomato extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans vitamin a supplementation in children with poor vitamin a and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron lignan and isoflavone excretion in relation to uterine fibroids: a case-control study of young to middle-aged women in the united states zinc supplementation does not affect growth morbidity or motor development of us term breastfed infants at c0 mo of age optimal vitamin d status and serum parathyroid hormone concentrations in african american women synergy between mannose-binding lectin gene polymorphisms and supplementation with vitamin a influences susceptibility to hiv infection in infants born to hiv-posit.. co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men patterns distribution and determinants of under- and overnutrition: a population-based study of women in india association between dietary glycemic index glycemic load and body mass index in the inter study: is underreporting a problem? viva la familia study: genetic and environmental contributions to childhood obesity and its comorbidities in the hispanic population predictors of nutrition counseling behaviors and attitudes in us medical students

Trying to find Raptors news this time of the year is akin to a polar bear hunting for seals in the middle of the summer, and if you know your polar bears, you’d know that’s very hard. Since the ice is all melted and watery, polar bears don’t have a platform to hunt for seals and can die of starvation. There’s no threat of starvation here because even if we don’t have actual Raptors news, we can rely on some I-only-care-about-this-because-there’s-nothing-else-going-on news, in the form of Chris Bosh insisting that he played hard and never gave up whilst in Toronto. I can believe that he thinks he played hard, but him saying that he “would have done anything to win” is a joke, if that were true he’d come back with a mask to play the Chicago game. Leaving opinion aside, I don’t even know why he’s even answering such questions to begin with, dignifying them with a response is a slight admission of guilt and he should realize that. Next time somebody questions him about his Toronto effort, he should simply point to the ridiculousness of the question and move on. It’s like when I go to lunch with co-workers and the money for the cheque is short, someone will ask, “Hey Arse, did you not put in enough?”. At that point, I don’t enter into a debate of whether I put my share of the money in, I just angrily retort, “What the *&^%? Don’t ask me dumb questions”. Case closed. It doesn’t matter how much money I had put in, the appearance of being greatly offended at the accusatory nature of the question has answered the question better than any response would have. Moving on to the other half of “The Killer Bees” (haha, Devlin, you salesman), Andrea Bargnani hasn’t been talked about much this summer. It’s because he’s in Europe playing with the Italian team, while others like Weems and DeRozan have been active in summer league and have paid a few visits to Toronto. If and when Jose Calderon is traded, Bargnani will become the top-paid Raptor and the spotlight on him will shine even brighter. This attention will be in sharp contrast to that received by the Young Guz (YGZ® – I will never use the phrase Young Gunz again). While greatness and expectations were thrust upon Bargnani the day he got drafted, YGZ® have gradually raised the expectations based on their play last year. Going into next year, the question of whose team it really is, will be answered. Either Bargnani will finally make an imprint on the team, thus forcing everyone to acknowledge that he is the man in Toronto, or YGZ® will pry the spotlight away. If successful, this could finally plant the idea in Bryan Colangelo’s mind that Bargnani might not be untouchable. The previous scenario assumes that the two parties won’t mix well, as was the case last season. It could turn out that Bargnani and YGZ® will form a great partnership and work like a well-oiled machine tuned to a perfect balance. As a fan, that’s what you hope for, but there’s a part of me that thinks that consolidating Bargnani and the YGZ® to function in the same team is going to be tough due to the polarizing style of their play. One of the ways a synergy can be achieved is through an equal distribution of offense. The 16.5 shot attempts freed up by Bosh’s departure will need to be accounted for. Supporters for the Bargnani cause will feel that a good chunk of that should go to the Italian, who hoisted up 14.3 FGAs per game last season. Others might suggest a more equitable distribution that sees the guards’ thirst for the ball be quenched, maybe DeRozan’s 6.6 attempts should increase to around 14 or so. After all, this is a guard-dominated league and there isn’t much point to having a “star” shooting guard that doesn’t shoot enough. The commonly held belief is that your best player “deserves” the most shots, and that may be true, but if you compare the Raptors’ FGAs/player with the rest of the NBA, you notice that our shot distribution was simply too Bargnani-Bosh heavy. The Raptors had only two players averaging more than 10FGAs per game: Bosh (16.5) and Bargnani (13.4). When you compare the difference between first and third (Hedo Turkoglu with 9.1), the difference is 7.4 shots – that’s a lot! Let’s look at other teams: You can see that even though the Raptors had the NBA’s 5th ranked offense, their shot distribution was skewed compared to pretty much every other team except Indiana where Granger dominated the shots, much like Bosh did in Toronto. The impact of a certain offensive style cannot be discounted on the defense; a team which shares the ball well on offense is likely to keep everyone happy and they’ll be willing to play more defense. Personally, I prefer organized team-ball than focusing your sets around one player, the offense in the latter gets boring and is much more liable to get shutdown during crunch time as defenses will focus on one players instead of worrying about multiple threat. Only one of the reasons why the first Raptors player to be seen on the “clutch stats” list is at #24. I’m not presenting these stats as solid proof of anything, merely killing the time and giving some ideas for discussion. I do however feel that these numbers need to straighten themselves out, the Raptors should have at least four players averaging 10 field-goal attempts a game: Bargnani, DeRozan, Johnson and one more. This would make for a much more balanced offense, better team spirit, and would motivate these guys to play better defense. Finally, thanks to everyone who contributed their stories yesterday, some really neat stuff.

“The essence that endures is more real than mere paint, but intangible..” For me, Aikido is not a watered down, collusional pretence of a dance. Not at all. It must never be forgotten that Aikido has its origins in valid battlefield combat jujutsu of the most virulent kind. Aikido’s forte lies in the fact that the aikijutsu arts continued to refine jujutsu and pare away the excrescences to reveal core principles that optimize efficiency, leverage and economy of motion to their best. And perhaps more. When practiced with martial integrity, that is, unmitigated honesty, Aikido purges mental clutter and entanglements, to produce clear thinking. This is a never ending process. Because it maintains an honest body-mind connection this produces a unique synergy that opens up a Way and enables clarity of perception. Why does it enable? Nature creates by overcoming challenges, not as in slapping paint on a canvas then expecting it to last. Nature is constantly reworking and changing. The essence that endures is more real than mere paint, but intangible. When you are going home from the dojo, where is ikkyo? Where is iriminage? Where are.. the things you just practiced? Much like a more dynamic form of sand art, everything changes and disappears into impermanency, yet the essence remains. Whilst invisible it is more real than the appearances that are swept away. What remains, albeit unseen by many, are the predispositions which are keys to all Creation. These open up an entirely different view to existence to enable an harmonious and debt free way to negotiate life. However this awakening attitude must be maintained vigilantly and constantly fine tuned for optimal performance, just like any engine. Daily training becomes the Way. “There is no enemy of love.. There is no time and space before Ueshiba of Aikido.. only the universe as it is..” Morihei Ueshiba

PDC Energy (NASDAQ:PDCE) has done alright since January of this year, even though concerns remain about the quality of the company's acreage and opportunity in the Utica. These shares have risen about 15% over that span - not bad relative to the group (as measured by the EPX), but inferior to other Wattenberg operators like Bonanza Creek Energy (NYSE:BCEI) and Synergy Resources (NYSEMKT:SYRG) and more diversified operators like Whiting (NYSE:WLL). While these shares still appear to be undervalued, concerns about rising unit LOEs, litigation, and inconsistent Utica drilling results may all remain as headwinds and/or risk factors for the shares. Wattenberg - Dialed In And Delivering PDC Energy is the third-largest... |FREE||SA PRO MEMBERS| |IDEA GENERATOR||X||Exclusive access to 10 PRO ideas every day| |INVESTING IDEAS LIBRARY||X||Exclusive access to PRO library of more than 15,000 ideas| |SECTOR EXPERT NETWORK||X||Exclusive access to all sector experts for direct consultation| |PERFORMANCE TRACKING||X||Track performance of all PRO stock ideas| |PROFESSIONAL TOOLS||X||Professional Idea Filters to zero-in based on industry, market cap and more|

The American electric automotive and energy storage company, Tesla Incorporated has announced that it has reached a deal to take over the solar energy company, SolarCity for a price of $2.6 Billion. According to the innovative Chief Executive Officer of Tesla, Elon Musk, the acquisition of SolarCity is meant to strengthen the balance sheet of the two companies, allowing them to build an integrated product that combines electric vehicle charging, solar power, energy storage, installation and servicing of the whole system, creating a renewable energy boom. The deal was agreed on Monday August 1st, 2016. Already, Mr Musk is serving as the chairman of SolarCity’s board. He also has family ties with the Chief Executive Officer of SolarCity, Lyndon Rive. Some critics of the takeover said a conflict of interest might have occurred during the negotiations stage, due to the close ties of Musk with SolarCity. Tesla is a public company, who trades on the National Association of Securities Dealers Automated Quotations under the symbol TSLA. But Musk revealed to Ars Technica that he had been rescued from the financial calculations, which determined the amount of stock Tesla paid for SolarCity. He said the solar company would be obligated to accept the best deal for its shareholders, even if that deal was not with Tesla. According to Musk, if the two companies do not merge, but decide to pursue their visions on producing renewable energy and how to store it, it would be very difficult. He said he strongly believes that the merger is the best option for the two companies to be able to create a renewable energy that could be stored at the same time. Musk also said Tesla’s quest to increase renewable energy production is due to the rising level of energy demand around the world. He said: “As transport becomes electric, as heating becomes electric, the demand for electricity is going to increase”. Mr Musk added that his company’s manufacturing experience will serve as an advantage to SolarCity’s shareholders, saying the deal is the best for them. Financial analysts say per the terms of the agreement, SolarCity now has 45 days to shop for a better offer before the two companies formally present their merger intentions to shareholders and the Securities and Exchange Commission of the United States. The Wall Street Journal reports that Tesla will buy SolarCity in an all-stock deal that would give 0.11 shares of Tesla stock to investors for every share of SolarCity stock they own. The Journal also confirms that the deal is worth $2.6 billion. Tesla later revealed more details of the deal in a press statement. The company said the merger could generate about $150 million in cost synergies in the first full year, after the deal closes. Cost synergy, in the context of company merger, is the savings in operating costs expected after the two companies have come together. Both executives of Tesla and SolarCity said in the statement that the expected synergies would come from decreased marketing expenses and the ability to leverage Tesla’s retail footprint by selling SolarCity panels in Tesla stores, as well as reducing the cost to service customers by consolidating service visits. Currently, SolarCity is in the process of building a $750 million solar panel factory in the city of Buffalo, New York. The factory is expected to be completed in 2017. Tesla is speeding up process to complete its Gigafactory in Neveda, which will be capable of delivering up to 150 gigawatt hours of battery storage per year. This project is expected to be completed in 2020. Already, Tesla has completed the manufacturing of batteries that are capable of storing energy for future use. Renewable energy advocates have praised the deal between the two companies, saying it has added momentum in the drive to obtain clean and cheap energy in the future. Thanks for taking the time to read this article. If you found this information helpful, please share it with your friends and family. Your support in our endeavor of sharing free information would be much appreciated.

Mirvish Gehry Toronto condos description Mirvish Gehry Toronto is a new condo project at 260 King Street West(King St W & Simcoe St) in Toronto, will be developed by Mirvish Productions and Projectcore Inc. Mirvish+Gehry Toronto Condos has 2 buildings with a total of 2000 units and 92 Storeys. From Mirvish/Gehry Toronto: A powerful creative synergy is set to transform Toronto’s iconic King Street arts and entertainment district. David Mirvish and Frank Gehry have joined forces to unveil a bold new vision for our Cultural Corridor, with the creation of a new public gallery, cultural and educational facilities, residential and business spaces. The inspired vision will see King Street evolve into a thriving, livable urban community, a great address to come home to and experience the finest in art, culture, design and life that Toronto has to offer. Mirvish+Gehry Toronto condos project summary PROJECT NAME: Mirvish Gehry Condos ADDRESS:260 King St W, Toronto PROJECT TYPE: Condominium DEVELOPER(S):Mirvish Productions and Projectcore Inc. ARCHITECT(S):Gehry International, Inc. NUMBER OF BUILDINGS:2 ESTIMATED COMPLETION DATE: TBA Mirvish+Gehry Toronto condos location map 260 King St W, Toronto

Top Trinidad and Tobago swimmer George Bovell says he is mentoring FINA World Youth silver medallist Dylan Carter even as he prepares for his Men’s 50m freestyle event at the 2014 Commonwealth Games in Glasgow, Scotland. The two-man T&T swim team starts its campaign from the first day of competition at the Tollcross Swimming Centre from Thursday to next Tuesday. Carter, the World Youth Men’s 50m butterfly silver medallist, will be swimming the 400m freestyle on Thursday and the 200m freestyle on Friday, while Bovell prepares for swimming’s blue riband event whose preliminaries are on Monday morning. Carter is also part of the national team for the Youth Olympics in Nanjing, China next month. In an Amateur Swimming Association of Trinidad and Tobago media release, Bovell said Carter reminds him of himself when he competed at the his first Olympics in Sydney 2000. “Dylan Carter is here with me, he is my roommate. His enthusiasm makes for a synergy between us. He is very receptive to the hard-gained insights I am passing on, well prepared and is looking great in the water. “I am excited to see him swim as he competes in the 200m and 400m freestyle events. Dylan (Carter) reminds me of myself when I first started representing T&T at the open international level under the mentorship of Sebastien Paddington. Now my role is reversed as I am the mentor to the next generation and I hope to help him break my 200m freestyle open record, which has stood for too long. I expect to see him in the finals, potentially on the podium, his competition is very stiff here and will be exciting to follow,” Bovell said. Bovell added that the calm , friendly atmosphere is about to give way to fierce and exciting rivalry in the different disciplines. “It is important to be aware of this and to remain relaxed, calm, and humble because nothing is certain and there is still much work to do. We should never become complacent and lose sight of our goals. The physiological aspect of my performance is perhaps the element of the equation that I have the most control over, it can very often make the biggest difference in affecting the outcome of stressful situations. This physiological tenacity is something that comes with experience gained from having been in similar situation many times before. I intend to exercise full control of it by practising deliberate thinking, and to achieve technical excellence in the multitude of small details that comprise the race regardless of how fresh and fast, or heavy and stiff my body may be feeling,” the 2004 Olympic bronze medallist said. Bovell , the 2013 World Championship Men’s 50m free bronze medallist said that though his form hasn’t been great coming into the Games, he has made adjustments to fine tune his preparation ahead of the 50m free. “The gold medal in the 50m freestyle is still far from my grasp. There is a lot of competition as this is the closest (most competitive) race in sport. I will admit that lately my form has not been as great as it needs to be. I came into this season inspired by my success last year and with this intensity I actually managed to become overtrained and too broken down and have gained some impressive endurance that has come at the expense of my speed. To counter this lately over the last two weeks, I have really dropped the volume and kept some of the intensity in my training in an attempt to let my body recover,” Bovell explained.

DSM partners with ERDA on engineering plastics and application research for the Indian electrical industry Royal DSM, the global Life Sciences and Materials Sciences company, announces that its subsidiary DSM India Pvt. Ltd, in Pune, has signed a Memorandum of Understanding (MoU) with ERDA, the Electrical Research & Development Association, covering basic research in the field of electrical applications. ERDA, a cooperative research institution created by the Indian electrical industry and utilities with support from the governments of India and the state of Gujarat, has its main office in Vadodara. The MoU covers various activities intended to help develop new eco-friendly sustainable engineering plastic solutions for the electrical industry. DSM has a strong record of development and production of engineering plastics for electrical applications, and is a leading global supplier of high performance polyamides and polyesters for the sector; ERDA has state-of-the-art test facilities dedicated to the electrical industry. Both organisations have a strong commitment to research with highly qualified people, and expect mutually beneficial collaboration across several disciplines. DSM and ERDA will cooperate in three areas in particular: firstly, they will engage in joint development projects on various topics of mutual interest, focusing on new innovations and studies that can have a positive impact on the environment, performance and affordability; secondly, technology testing programs will be established to prove that materials meet application requirements; and finally, exchange programs will be set up to enhance the capabilities and knowledge of both organisations. “A technical partnership between DSM, with its specialization in engineering plastic materials, and ERDA, with its competence in application engineering in the electrical engineering domain, forms an ideal launch pad to yield improved products in the market place,” says ERDA Director T.P. Govindan. “It is hoped that the synergy in the partnership will prove beneficial to both partners and society at large. We look forward to making the partnership a defining milestone for both of us.” At DSM, Rein Borggreve, Global Research & Technology Director for Engineering Plastics, highlights the group’s extensive network of partnerships with the best universities and institutes around the globe on a diverse series of topics, ranging from food ingredients to automotive. “We are very happy to enter into this new cooperation with ERDA, a leading institute in the field of electrical applications,” he says. “We are confident that it will lead to innovative solutions on performance and sustainability.” “DSM applies Bright Science to make people’s lives better, safer, easier and healthier. We continue to develop sustainable and innovative solutions that address key global challenges, based on our portfolio of high performance materials for many different markets and applications, and obviously the electrical sector is a very important area of interest for us.” Sanjay Jain, Business Director of DSM India’s Engineering Plastics Division, says: “The partnership with ERDA will further explore the use of engineering plastics beyond today’s frontiers in the Indian electrical industry by providing innovative sustainable solutions, further reinforcing the leadership and knowledge base that both parties have in the industry today.” DSM is a global leader in engineering plastics for the electrical industry, offering innovative and sustainable material solutions. It believes that the support provided by ERDA will help it in many ways, especially in developing the Indian switchgear market. The competencies of the two organisations are fully complementary and should lead to new, validated solutions specific for the Indian market. DSM regards the search for sustainable solutions as a key driver for success and profitability. In addition to reducing the environmental footprint of its own operations by reducing energy consumption and greenhouse gas emissions, it is also driving sustainability via the engineering plastics it produces and in the applications for which they are used. It has identified four key sustainability drivers for its engineering plastics business: a reduction in the carbon footprint of its materials and their applications; the elimination of substances of hazardous concern; recycling as a route to “cradle to cradle” solutions; and development of bio-based polymers that can perform in critical technical components. More information can be found at www.dsm.com/electrical-electronics.

Dragonair CEO Patrick Yeung, in the Dragonews Mar-Apr-2012 issue, acknowledged (Apr-2012) the challenges in the aviation sector. He stated, "amid this good news I am afraid that I do have to sound a cautionary note. As you are all aware, the aviation industry is highly volatile and we can very quickly feel the effects of situations and incidents that are beyond our control. While the economic outlook in Asia is encouraging, that in the US and Europe remains sluggish and this has a knock-on effect around the globe. We are especially beholden to rises in fuel prices, and this of course comprises a huge amount of our budget, along with inflation". [more - original PR] Dragonair: "We are also operating in an increasingly competitive atmosphere here in Hong Kong. One downside of an economically active environment means that everyone wants a share of the pie! And Hong Kong itself is facing competition from other destinations in Asia that are trying to capture business both within and outside the region....It is vital that we make the most of Dragonair’s competitive edge. The key to facing all these challenges is the synergy that comes from KA and CX working closely and effectively together. By strengthening this connection, we can maximise the KA network, fortify the HKG hub, capture more passengers and business, and hence grow further," Patrick Yeung, CEO. Source: Company statement, Apr-2012.

It's not scientists who find the first signs of life on Mars. It's wizards... In A Wizard of Mars, Kit and Nita find themselves caught up in the search for the answer to an age-old question: were there ever Martians, and if there were, what happened to them? As they work with an elite team of wizards who find a mysterious "message in a bottle" that holds the first hints to the secrets of the Red Planet's long-lost inhabitants, Kit's long-standing fascination with all things Martian initially seems like an advantage. But when the "bottle" is uncorked and life emerges once more to shake the Red Planet with its own perilous and baffling brand of magic, Kit unexpectedly becomes enmeshed in a terrible, age-old conflict -- turning him into both a possible key to its solution, and a tool that in the wrong hands shortly threatens the whole human race. Now he and Nita must fight to understand and master the strange and ancient synergy binding them to Mars and its last inhabitants… before the history that left Mars lifeless repeats itself on Earth.

Leeds-based marketing agency Think is celebrating its expansion into Dubai. Investment from ENG – one of the largest visual communications and multimedia solutions companies in the UAE – has given Think the opportunity to consolidate its global marketing offering. Less than three years after its foundation in 2005, Think now incorporates offices in Yorkshire, London, New York and the Middle East. After working with Think as its branding consultancy, ENG’s MD soon identified the potential to introduce a superior agency into the UAE market. With a strong synergy between the two brands and a desire to deliver unique solutions for clients, , part of ENG was born. The move has enabled THINK to establish individual departments dedicated to branding, marketing, design, PR and research, all of which can be offered internationally, managed under Global Strategy Director Michelle Edgar-Parsons. Paul Inman, Think MD says; ‘This is a hugely exciting time for us and from our HQ in Leeds we’re seeing our global ambitions realised. My priority has always been to find exceptionally talented people who genuinely love what they do and never stop searching for new ways to do it, and the relationship with ENG is testament to that. ‘We have always let our results do the talking and I believe the marketing industry in Dubai needs our fresh approach. While it has experienced a significant boom in the volume of agencies, the perception is that quantity is taking precedence over quality and strategic thinking is lacking. THINK has never been afraid of a challenge and we plan to expand our horizons into Egypt, China and India in the coming years. We will do this with zeal, intelligent insight, creativity and devotion.’ Think has already won several high-profile UAE accounts including a re-brand campaign for Dubai’s newest radio station Coast 103.2 fm and brand development for global property pioneer Ruwaad. Clever Thinking has arrived. For any further information please contact: Klara Zakis-Global PR Executive Work Mobile: 07918756287 Work Landline: 01924 456 404 And because we’re celebrating, we wanted to give you something to smile about too Enter our media-only competition to win a trip for you and one friend to Dubai. Visit http://holiday.thnk.co.uk from Thursday 13th, for details of how to win a bespoke holiday, designed with your passions in mind. If you like life with zeal, then enjoy the ride of your life on an extreme sports adventure. Totally devoted? Then devote some time to you with a pamper-perfect spa break. Consider yourself a cool customer? We’ll give you access to some of Dubai’s most exclusive hotspots. Or if you’re a fan of all things contemporary, you’ll be visiting the most exciting developments and shopping centres and seeing some of the world’s most iconic architecture. Check out 12ahead, our brand new platform covering the latest in cutting-edge digital marketing and creative technology from around the globe. 12ahead identifies emerging trends and helps you to understand how they can apply to modern-day companies. We believe 12ahead can put you and your business 12 months ahead of the competition. Sign up for a free trial today.

A toilet which doubles up as a goalkeeper? What a natural synergy! In Japan anyway. The Super Great Toilet Keeper is a collaborative invention of toilet maker TOTO and a sports lottery company called toto (same spelling, lower case). The toilet uses high speed motion cameras to detect the trajectory of the football. The toilet then very quickly tilts and fires out another ball to intercept the kicked football. It can react to balls shot at 160kph. The collaboration is intended to highlight both companies’ contribution to the environment, apparently. Watch veteran Japanese striker Tatsuhiko Kubo pit his wits against this clever lavatory.

The Choice of a Career They say, “Choose a job that you love and you will never have to work a single day in your life.” Such is the enjoyment one feels in working when the choice of what work to do, is a correct one. The average working span of an individual’s life spans about 50 years which is a formidable half a century. As such, it is an imperative that the choice of a career should be made with much deliberation and precision. In choosing a career, you may consider: • Doing things you would do for your wherewithal to earn a living. • Doing things that you love to do. • Your secret life and hence what you may want to do with a strong passion, eventually. In whatever way you shape your life, eventually what remains critical is your happiness. Your internal strengths, aptitudes, interests and desires need to be weighed with external opportunities that come your way at the job as also in the career that you will choose to pursue. The important thing here to be remembered is that a there is a difference between your job and career. While your job is something that you could be doing for a while, your career is a long term vision, the reason d’etre of your existence , your destiny, so that your life is rewarding and fulfilling. The first step in this entire process is to belong to an institute of higher learning which not only has relevant, basic infrastructure and technique but also can facilitate holistic growth. It should be able to provide knowledge, course-ware and pedagogy for its application, facilitating integration. A place where you learn-unlearn-relearn, for your todays and tomorrows. It is an imperative to also develop critical skills to be used at various levels. Primarily , the skills would be at the :- • Social Level- for personal and professional interactions. • Professional Level – for integrating theory with practice. • Technical Level – provide interface with technology at critical junctures. For a student of today’s world, there are many institutes available, and most of them will provide you with one or the other skills but very few will encourage you to develop all three skill platforms in synergy. During this learning phase, it is crucial that you, as a student are able to hone attitudes and imbibe soft skills so that you can perform effectively and efficiently from the start. Other skills that need to be learnt and internalized are: • Time and stress management- through prioritizing and scheduling work and study. • Accountability for your work and yourself. • Imbibing responsibility- response to ability. • Building a sense of self confidence and conscientiousness. • Developing clear thinking. • Building a positive attitude. While at your institute, you must be able to develop your network of relationships through school and its alumni, at various forums and at work during projects, apprenticeships and internships. An institute that provides for building relationships continuously over time is high on the opportunity platform. Nurturing self discovery – a process of internal rejuvenation and constant realization of your mission, is the essence of growth. This is achievable through introspection, experimentation and the cycle of experiential learning. Any institute which helps you with these fundamentals of life and career, helps you to grow over the years, grow continuously and is akin to a home where you want to be. If you can work your way towards a career that helps you build a future that is aspirational and happy, then it is going to be a very satisfying life at the end of the road. Prof. Ramola Kumar Dean, The Delhi School of Communication Prof. Kumar’s Profile: Prof. Ramola Kumar started her career at The Institute of Management Studies, Bikaner as the Head of Department in the year 1984. She moved in October 1985 to The Institute of Management Technology, (IMT) Ghaziabad as Professor, Marketing with additional responsibilities as Academic Coordinator-- for 4 yrs. In 1989, she shifted to IMT Delhi center as Chairperson, Evening Programme. She headed the center for 6 years and for a span of 5 years during the same period, she was the Marketing Course Coordinator at The Times School of Marketing. Presently, Prof. Ramola Kumar is the Dean, The Delhi School of Communication wherein she was instrumental in helping conceive and launch the programme in the year 1995. The Delhi School of Communication is one of the premier institutes in the country in mass media studies and integrated communications. Her areas of specialization include Marketing,Brand Management and communications. Prof. Kumar has been educated in the United States of America, Canada and India. She pursued her MBA from the University of Ottawa, Canada and was ranked 4th in the management programme.

Michael Kaiser, M.D. Mr. Chairman and members of the committee, my name is Michael Kaiser, I am a pediatrician and Acting Chief Medical Officer of the LSU Health Care Services Division, which consists of seven acute care hospitals and extensive outpatient clinics operated by the State of Louisiana. These include our rebuilt LSU Interim Hospital campus in New Orleans, which prior to Hurricane Katrina was a component hospital of what was legally known as the Medical Center of Louisiana-New Orleans and which was effectively destroyed by Hurricane Katrina. Similar to other local public hospitals across the country, this facility functioned as the core of the safety net for the uninsured and was the predominant site for the clinical training of physicians and other health care professionals. The now closed Charity Hospital (the other component facility of what was the Medical Center of Louisiana at New Orleans) sits across the street from the VA Hospital, which also suffered catastrophic damage in the storm. Following Katrina, nothing has occupied our time and attention more fully than the restoration of our public hospital and its clinics to serve the people of this region and the future health care professionals who train there. Of necessity, LSU has focused on both the present and the future. In the nearly two years since Katrina, we have moved from emergency facilities in tents to the opening of a small, interim hospital and a growing number of primary and specialty care clinics at several locations. Our capacity is not yet up to the level of need in the region, particularly in the availability of psychiatric services, some medical specialties and dispersed primary care clinics, but we have made significant progress. Other major additional steps will be taken in the months ahead. As we continue work to address immediate and critical needs in the community, LSU has kept a steady focus on the longer term. The region desperately needs not only additional health care resources, but also a way to develop and deploy those assets through a better, more efficient system than was possible before the storm. LSU has long worked toward fundamental improvements in its delivery system, such as through its award-winning disease management program, but the convergence of the need to rebuild and the heightened support today for both a reformed delivery model for care to the uninsured and for the financial and reimbursement reform necessary to make that new model possible, present realistic opportunities for our long-term agenda for change. The VA Collaboration The potential collaboration between the Department of Veterans Affairs (hereafter VA) and Louisiana’s state public hospital system is one propelled by unintended opportunity, but it is a core part of our strategic vision. We have a chance to jointly design and cooperatively operate a new facility that meets the needs of both institutions, and the patients they serve, while at the same time achieving significantly enhanced efficiency, cost savings and quality health care. The proposed collaboration is a logical step for reasons that extend beyond the destruction of Katrina. The adjacent VA and Louisiana-operated public hospitals have a long history of working together. Prior to the storm, the New Orleans VA purchased over $3 million a year in clinical and other services from LSU, including Cardiothoracic Surgery, Radiation Therapy, and Dermatology services. Many physicians worked at both the VA and the Medical Center of Louisiana at New Orleans facilities and many medical residents, from both LSU and Tulane Schools of Medicine, rotated to both hospitals. For the past 18 months, I have chaired the planning efforts with the VA. First, the Collaborative Opportunities Study Group, co-chaired with Mr. Michael Moreland, Director of the VA Hospital in Pittsburgh, looked at the possibility and feasibility of building together and sharing services. Once proved feasible, the Collaborative Opportunities Planning Group, co-chaired with Mr. Ed Tucker, Director of the DeBakey VA Hospital in Houston, has been studying what services should be shared and the details of building together. The COPG continues to meet weekly in order to present a final report to the Secretary by the end of September, 2007. The creation of a VA-LSU campus in downtown New Orleans will create benefits for both partners that exceed what either can accomplish separately in different locations. We have a rare opportunity to develop a whole that is greater than the sum of its parts. There are enormous benefits to the community of a downtown medical complex anchored by the VA-LSU collaboration, bolstered by the Tulane and LSU health science centers, and building on a Level I Trauma program and centers of excellence in orthopedics, neurosciences and other specialties. These benefits will redound specifically to the patients of the VA and LSU systems, as well as to a larger population. It is the synergy created by working together that will enhance the services available to all our patients. Where The Project Stands The Louisiana Legislature in its just completed 2007 Regular Session, approved capital outlay appropriations totaling $1,500,000,000 for the project ($74,500,000 in HB 765 of the 2007 Regular Session and $1,425,500,000 in HB 2 of the 2007 Regular Session). These appropriations overstated the financial requirements for the facility by $300,000,000 because the legislature failed to make an adjustment for $300,000,000 previously allocated for this project, but moved in the waning days of the legislative session to the Road Home Program. Adjusting for this error leaves $1,200,000,000 for the new academic medical center which matches the cost estimate for the facility contained in the business plan completed by the Adams Group, a national hospital consulting firm, and overwhelming approved by both houses of the Louisiana Legislature. This funding comes from multiple sources as follows: $74,500,000 is from the State General Fund that is available immediately for land acquisition, planning, and construction; $225,500,000 will come from the sale of general obligation bonds that will be issued by the state as the need for additional cash becomes available; and, the final tranche, $900,000,000 will come from the sale of revenue bonds that will be issued after the general fund and general obligation bond monies have been expended. The construction of the new academic medical center is being managed by the Office of Facilities Planning and Control which is an agency within the executive branch of Louisiana government. Acquisition of land identified for the new academic medical center and the VA facility is already underway with contracts having been issued to complete title and appraisal work. Once the VA firmly commits to building at the downtown site, the City of New Orleans and the State of Louisiana are prepared to immediately proceed with land acquisition for the VA. Both LSU and the VA have conducted independent architect selection processes and are ready to announce the winning firms. If the same firm is not selected by each partner, a previously developed plan to work together with separate architects will be implemented. From this point forward and given the preparation of both partners, the process of building a new hospital complex together can proceed as quickly as choosing to build separately. Significant groundwork has been laid for a long term, mutually beneficial collaboration, and we are poised to see it to completion. Thank you again for your interest and for this opportunity to share LSU’s perspective on these critical matters. Far from being an obstacle to health care reform as some have feared, the creation of a revitalized academic medical center complex in the city will be a catalyst for that reform. Particularly if LSU and the VA work together, it also will sustain a reformed system in the long run by supporting a viable, mission-driven system dedicated to improved access, the highest quality medical care and innovative health care education in a rebuilding community.

Phantoms Foundation Launched a Catalogue of Graphene Companies Worldwide (Nanowerk News) Phantoms Foundation is pleased to announce a catalogue of companies working on Graphene launched during the International Conference & Exhibition Graphene 2014 (Toulouse, France) back in May. The first edition features only companies working directly on the field. The second version (2015) to be launched during Graphene 2015 (10-13 March, 2015) will include all those who work hard in Universities, Research Centers, etc. This initiative comes as an open platform resource to attract global participant’s intent on sharing, exchanging and exploring new avenues of graphene-related scientific and commercial developments. The main goal is to have a source in hand where it would be possible in just one file have an overall view of which companies develop their work on the field. This catalogue gives an overview of the companies performing working on Graphene and will be a way to promote interaction and future partnerships. It will also serve mainly as a valuable source to investors, end-user companies, policymakers, etc. It will be a way to promote interaction, synergy and future collaborations for new ways of scientific and commercial developments related to graphene. At present, the records of 65 companies are featured on this first catalogue. The catalogue was available during Graphene 2014, the largest European event on the field, held between the 6 and the 9 of May. A PDF version is also online to download at: www.grapheneconf.com/companies_catalogue/ (registration required). About Phantoms Foundation This Non-Profit organization was established in 2002 (Madrid, Spain) in order to provide high level Management profile to National and European scientific projects. This association plays an important role in the 7th Framework Program as a platform for European funded projects to spread excellence amongst a wider audience, and to help in forming new networks and was involved in 11 European projects in the last 10 years either as coordinator (nanoICT CA) or partner. Phantoms Foundation is now a key actor in structuring and fostering European Excellence in “Nanoscience and Nanotechnology”, having a world leading position in organizing International conferences, training and dissemination activities in this field. Over the past years has been deeply involved in Graphene related activities. www.phantomsnet.net

Henry Tang backers set to form powerful Legco bloc Pro-business group Economic Synergy is apparently leading the race to court independent lawmakers to strengthen its clout in the new Legislative Council. The group may forge an alliance with four other legislators to create a bloc at least seven strong, which would make it the second-biggest political grouping in Legco. Economic Synergy has three representatives in Legco - Jeffrey Lam Kin-fung, Andrew Leung Kwan-yuen and Lau Wong-fat. All nominated Chief Executive Leung Chun-ying's rival Henry Tang Ying-yen in the race for the top job in March. Lam spearheaded the formation of the Business and Professional Alliance - a loose group of 12 pro-establishment lawmakers - last year. He said yesterday he had been discussing re-forming it, but refused to confirm whether it would involve his Legco neighbours Lo Wai-kwok, Christopher Cheung Wah-fung, Abraham Razack and Priscilla Leung Mei-fun. "We have agreed to sit together for a reason," Lam said. "[We] have similar thoughts." If the four agree to join, the bloc will command more votres than the Federation of Trade Unions, the Democratic Party and the Civic Party, all of which have six members in Legco. It might also mean that Economic Synergy wins the battle against a possible revival of the pro-Leung "Breakfast Group". The original Breakfast Group was dissolved in 2004. One of its members, Ng Leung-sing, who has been returned as a lawmaker after an eight-year hiatus, is said to have been trying to revive it, but it is believed he has only secured support from two other independents - Ma Fung-kwok and Martin Liao Cheung-kong.

Zen Flesh, Zen Bone: Von Schweikert Research VR-4 Generation II Speakers by Greg Weaver The Zen experience Zen might well be described as a form of monastic humanism, a spiritual directive for self-actualization or self-knowledge. Robust, earthy and energetic, when Indian Buddhism was first introduced into China in the first century AD, it reacted against the tendency of each of the competing Buddhist sects to favor one particular scripture, and in general, it opposed heavy reliance upon sacred texts. According to Buddhist tradition, men of lesser understanding might need the aid of words and scriptures. Zen Buddhism, however, in the highest sense, was wordless. Tradition says that once, as Buddha sat in his garden and turned a flower in his fingers, only one of his attending disciples, Kashyapa, in an instant had understood all that was meant by that act. This understanding brought a smile to Kashyapas face, so Buddha chose to transmit his enlightenment to him, wordless and directly. In symbolic tradition, this formal act of transmission has been preserved in Zen in various ways over centuries. What does all this have to do with a pair of loudspeakers? Read on. My time with the newest version of the VR-4 from Von Schweikert Research gave me cause to reflect upon my introduction to and subsequent grasp of Zen in the early 70s. At the dawn of my studies, there was plenty of hard work in the form of many tasks that had to be undertaken with little understanding or meaning. Then came loads of "practice," in the form of zazen, the ritual sitting associated with meditation, again undertaken with little understanding at first. With time, there came the glimmers of awareness as I learned patience and purpose. Finally, after some considerable duration, there came the joy and the revelation that I had struggled for and anticipated, allowing all the work and purpose to be seen in the proper perspective as I looked back upon the learning experience. So it was with the Von Schweikert Research VR-4 Generation II. They required much attention to placement when they first arrived, only gently revealing themselves to me as I slowly honed in on the more correct room placement. They also exhibited many changes of voice before allowing me to see their special vision. They were moved here, there and back again. They were paired with this amp and those cables. Once all the movement, run in and partnering had been accomplished and a final synergy attained, they took me on a unique trip to magical place--a musical satori, if you will. Undertaking the pilgrimage Transporting the Gen. IIs home is no easy task given their collective 270 pounds--without packing material! Thankfully they come in four boxes, making the toting and schlepping a bit easier. Equally as thankfully for me, UPS brought them right to my driveway, simplifying my chore considerably. To top it all off, I was fortunate enough to have the help of Casey McKee, Sales and Marketing Director of the Hales Design Group, who happened to be visiting me that afternoon, to get them into my listening room. Thanks Casey, I owe you one! Unpacking them revealed my audition set to be of an absolutely beautiful red-cherry finish, a finish to which no photos I have seen can do justice. You must see them to appreciate the lush color and satin-gloss finish. The significant other, who typically couldnt care less about my audio fetish, even took time out to remark on their beauty. That is saying something. Assembling the speakers is truly a snap. There is a rectangular wooden frame atop the woofer bases, bearing the VR logo on the front span, and providing for the exact placement and snug fit of the mid/tweeter modules. The huge woofer ports flare rather elegantly to 5.5" off the back of the module, eliminating any chance of turbulent air noise where they couple to the room. The woofer cabinets five-way binding posts reside in a 3"-by-5.5" recessed mounting plate near bottom of the unit. Once the mid/tweeter module is placed atop the woofer base, its input posts, also located on a 3"-by-5.5" recessed mount plate, reside some 34" off the floor on the uniquely sloped rear panel. With nearly a 30" difference between the two sets of input posts, get yourself some long jumpers if you intend to single-wire the speakers. Or, better yet, take the hint and biwire. Youll be glad you did! If you are interested in greater detail of the design and execution of the VR-4 Gen. II, see last months preview. The latest iteration of the first Virtual Reality speaker offered from Albert Von Schweikert retails for $3950, just $500 more than the original VR-4. My current analog front-end is the venerate Linn Sondek LP-12 (with my own modifications) fitted with a Magnepan Unitrac 1 carbon-fiber, uni-pivot-tracking tonearm tipped with the superlative Monster Cable Sigma Genesis 2000 moving-coil cartridge. Ones and zeros are generated by a Pioneer Elite PD-41 stable-platter transport and sent via coax to an Audio Alchemy DTI Pro 32, then on to an Audio Alchemy DDE v1.2 via I2S bus, both of which are powered by an Audio Alchemy Power Station 2. All the AA equipment sports the full Dusty Vawter treatment. Both front-ends feed my Threshold FET nine/e which then drives any one of a number of amplifiers which include the wonderful Pass Labs Aleph 2 and the Clayton S-40. All single-ended cables are either my home-brew SSTs or the astounding JPS Labs Superconductors. Digital cables include my home-brew "Silver Bit Transfer" or the SRM Max 1. Speaker cables are the Superconductors from JPS Labs, or the MI2 or AG1 from Alpha Core Goertz. Speakers include my beloved Acoustat 2+2 Medallions (with my own modifications) and, of course, the VR-4 Gen. IIs. My listening room is 11' 2"W x 18'L x 7' 6" T. Room taming is achieved through the use of both Cascade Audio Engineering products and my own home-brew room-taming devices. And lots of inner tubes and sandbags! Sitting Learning to be still Set up on the other hand proved that the more attention you pay to placement, the better the VR-4 Gen. II will reward its owner. After two or three hours of fussing, I settled on a fairly pleasing position with the tweeters some 60" from the front wall and 29" from the side walls. My listening position is 12' 1" from the front wall and on the centerline of the room. This was the position for most of the break-in period, but many refinements were made thereafter, allowing the speakers to come completely into their own. Though the VRs seem nearly impervious to placement in regard to their ability to recreate a realistic presentation, they are like most other speakers in regard to tonal balance and when placed properly: They literally come to life. Although it is next to impossible to set the VR-4 Generation IIs up so that they sound horrible, it does take some attention to get them to disappear completely and validate that "Virtual Reality" moniker. Final positioning came with vast experimentation. After exhaustive testing and listening in two other very different rooms (belonging to the Gallo-meister and HAL), as well as the implementation of KB Acoustics highly effective Visual Ears room-analysis software, certain patterns began to emerge. The final listening position in my room ended up with the tweeter 53" from the front wall and just 18" from the sides. While this may seem a rather extreme position in terms of relationship to the side wall, the resultant benefits in tonal balance and bass performance more than made up for the small loss in stage depth. Such proximity to the side walls will obviously mandate the use of materials to tame primary reflections. While such room-taming devices were already in place at Chez Weaver (the Cascade Audio Engineering Whisper Wedges), I must tell you that room tuning will be an essential part of getting the best from any speaker in any room, including the Gen. IIs. Once you have gotten the overall balance accurately dialed in through correct room placement, it is time to examine the benefits of the rear-firing tweeter. While often able to enhance the soundstage depth and focus, it could at times unduly brighten the overall timbral balance. So you may choose to simply bypass its use by leaving it completely attenuated. You will really have to experiment with this to appease your own tastes, but do experiment. It can offer a wide range of effects, especially in terms of image specificity and stage size. I have selected both a great tonal balance and stage recreation by using about one-fourth of the gain available to that rear tweeter from the pot on the rear of the panel. Practice - The steps to enlightenment Right out of the boxes, the Gen. IIs were a bit hard and somewhat bright, more or less to be expected. I just threw my Environments 1: Psychologically Ultimate Seashore disc [Atlantic 81764] into the old transport, engaged the repeat button and pushed play. Although many tout using specialized break-in discs or tracks, I have found over the years that this disc works as well or better at achieving the desired results. As a matter of fact, recorded seashore sounds are a favorite of renowned cable guru and set up man George Cardas, About a day later, I sat down in front of the VR-4 Gen. IIs with the intent of finishing some rough drafts. It didnt happen. I couldnt avert my attention from the music. I was literally unable to listen casually or to do anything else...like write, read, take a drink, or even scratch my chin. Im quite grateful that breathing is an autonomic reflex, otherwise I may have forgotten to do it. These speakers just drew me into the music entirely, even though they had yet to run in completely. It was now completely obvious that I was in the presence of a very special The first real character change that I noted, a slight reduction of the brightness, was logged at about 30 hours. After about 40 hours, the bass began to open up and sound more full and detailed. Things continued to change, sometimes quite drastically, for the first 100 hours or so. After that point, and up until about 300 hours, very minor nuances were noted, but the overall character had settled in and been determined at about that 100-hour mark. After full run-in of the speakers, detail was presented in proper scale and resolve, the woofers had loosened up enough to really start to convey true weight and bloom of instruments like cello and double bass, and the balance from lowest to highest octave had smoothed and poised. Hmmm, time to get serious. Cognition - Refining revelation There are a number of notable similarities between the original VR-4 and the Gen. II. Both designs use a single and critically chosen treated carbon-fiber driver to reproduce nearly four octaves of the music, the critical mid-band from 125Hz to 3.5kHz, which in my opinion is paramount to the smoothness and musical success of both incarnations of this speaker. Expanding on its triumphant predecessor, the Gen. II offers an apparent seamless integration of the many drivers. I know that last sentence is small, but the result of the effect I am describing is anything but insignificant, so you may want to read it again. The resultant level of coherence the VR-4 Gen. II offers is as seamless as I have ever heard from any dynamic loudspeaker. In this attribute, they come on par with my long-time reference, my modified Acoustat 2+2 Medallions, and best them in the lower registers. This is an achievement that will shame many well-known and MUCH HIGHER-PRICED loudspeakers. Bravo Albert and company! It also shares with the original an uncanny ability to provide a solidified image and coherent stage, which is where the VR (for Virtual Reality) in the nomenclature came from. The VR series recreate the phantom image and stage better than all but a few dynamic loudspeakers in my experience, ones that are many times the price of the VR-4 Gen. II. With the exception of a small hand full of electrostatic panels, I know of no speaker capable of delivering a more realistic My initial suspicion that the Gen. II would only slightly better the original VR-4 in areas other than aesthetics and foot print were rapidly dispelled. Cosmetically, the design of the new Gen. II, occupying less than 75% of the volume and only about 78% of the foot print of the original, provides the illusion that it is much smaller than it is. Its more diminutive stature is very seductive and has really refined the speakers overall appearance. Upon direct comparison to HALs original VR-4s, many vital sonic improvements became readily apparent as well. Namely, the Gen. II offered a much higher level of clarity and detail to upper midrange and high frequencies, greatly increased micro-dynamic and low-level resolution capability and faster, more articulate bass. The newly perceived speed and articulation to the lowest frequencies generated by the Gen. II are obviously attributes of the newly designed and executed woofer cabinet, with its latest labyrinth design and much larger and Albert is quick to point out that his new assistant engineer, Frank Derrigo, shares much of the credit for the Gen. II's success. Frank holds a Master's Degree from Clarkson in electrical engineering and has been working with Albert for about a year. Albert informed me that Frank spent over 200 hours evaluating different crossover parts and implementing small tweaks to the original global-axis-integration-network design, in addition to doing the fine-tuning on the new bass alignment. All I can say is that it was time well spent. The Generation II is easily a 50% betterment of the archetype. Making Bhodisattvas of us all I am still reveling in this newly found enunciation and integration. The speakers ability at resolving individual voices during complex dynamic passages is nothing short of astounding. The myriad of percussion instruments being played in the foreground of "Fair Game" from 1977s Crosby, Stills & Nash [Atlantic 19117-2] are easily outlined in their respective space, neatly and separately delineated. Try the opening of the "Malaguena" from Ravels Rapsodie espagnole [Classic/RCA LSC 2183-1] to see just what I mean. Or the cacophony that commences the first movement of Prokofievs Sythian Suite [Mercury 432 753-2], which is miraculously recreated in all its chaos, never stumbling or blurring. The driving "Metropolis Part 1" from Dream Theaters Images and Words [ATCO 92148-2] is some of the best-recorded material of its genre, and the VR-4 Gen. II is able to throw it all into perspective, then ride tight rein on the rigorously delineated stage. To paraphrase the 70s super group Yes and their song "Roundabout" from Fragile [Atlantic Import 050009], "Things come out of the stage and they stand there!" It is hard for me to believe that the Gen. II could best the original VR-4 in the area of micro dynamics and low-level resolution. That, in fact, was one of the VR-4s strong suits in my book. But the Gen. II easily surpasses its progenitor, proving to be supreme at this difficult task. About eight seconds into the opening of "Nanny Stick" by Andy Narrell from the Windham Hill Sampler The Boston Bass Disc [Windham Hill WD92-18], there is a struck cymbal which now just hung in space and time and decayed for what seemed like forever, fully 17 or 18 seconds. That decay was presented with a clarity and resolution Ive never heard before, even on my beloved electrostatic panels, long cherished for their ability to extract such low-level detail and micro-dynamic details. Listen to the subtle flavorings of the struck triangle in Steely Dans "Aja" from the same album [MFSL 1-033]. These delicate characteristics, often lost in the din of the rest of the complex arrangement by even the very best of loudspeakers, were wrested from the meticulously woven fabric of the composition. They were now seemingly given a life of their own just outside and behind the left speaker: distinct attack, glorious vibrancy and delicate decay. The muted time-keeping foot tapping of drummer Chris Layton from the superb Sony reissue of Stevie Ray Vaughans Couldnt Stand the Weather [Epic EK 64425] has never been better resolved. In the title track there are several breaks early in the cut where the band repeatedly stops and restarts. During these pauses, Laytons ever-so-low key foot tapping is so readily apparent and clearly outlined in space that you can almost tell what brand of shoes he is wearing. The musings of Ivan Morevec playing Beethovens Piano Concerto No. 4 in G Major [Via VAIA 1021] or Leonard Bernstein playing Chopins Fantaisie Impromptu [Sony SK 45818] are accomplished on a heightened emotive level, never leaving any doubts about the feelings or expressions being rendered. Piano keys, whether vigorously struck with their explosive attack or just brushed into a whisper, were presented with all the emotion and sensuality with which they were intended. Quiet hall noises, like creaking chairs, air-conditioner blowers, coughing audience members or closing doors are all revealed to be what they actually are rather than being offered up as some less-discriminate noise, in essence making the music that much more accessible. This attribute has the psycho-acoustic effect of allowing the subconscious to follow the flow of the music rather than be unintentionally and unwillingly distracted by the otherwise indefinable noise. In terms of low-level resolution and micro dynamics, the VR-4 Gen. II holds its own with any speaker in my several decades of experience, and in fact sets new standards in this price range. Lets talk about SLAM! You bass freaks out there are going to love this speaker. One note here, again about room placement: As with any full-range speaker, solid bass performance is ultimately dependent on room size, its resultant nodes and proper speaker placement therein. It is very easy to set the VR-4 Gen. II up in a manner that will provide less than impressive bass performance. Take your placement very seriously and you will be VERY well rewarded. Just throw on "The Invasion" from the Seven Years in Tibet Soundtrack [Mandalay/Sony SK 60271], "Tiger" from Paula Coles This Fire [Warner Brothers Imago 9 46646-2], or the "Maestoso: Allegro" from Saint-Sans Symphony No. 3 [RCA LSC 2341] and feel your room pressurize. The woofers, once broken in, are fast, articulate and go very deep. Response was only down 3dB at 25Hz and 10dB at 20Hz in my room. The use of two well-selected though relatively inexpensive 8" drivers over one larger (and slower) driver is well served. The fact that the speakers have delightful bass speed and extension simply serves the rest of the musical illusion by greatly enhancing the already pinpoint imaging and wonderfully spacious staging characteristics of the Gen. II. These are truly full-range speakers. While Im on the subject of deep bass, let me elaborate just a bit. While it is true that the low-frequency performance of the Gen. IIs is full range and surpasses that of the Gen. I, it is not the end all, or even world class for that matter. It is loose and poorly defined by those standards. Listening to the Kinergetics Research SW-800 subwoofers, as I did for some time, really spoiled me in that department. Using 10, 10" drivers (five per side) and tipping the scales at 350 pounds a pair, these exquisite subs have established my yardstick for measuring bass in terms of weight, detail and speed. Although the Gen. IIs provide satisfying low-frequency performance, this is without doubt their weakest link. But given the speakers price point and intended market, the level of performance they achieve is truly admirable. Some very well-known speakers tend to impose so much of their own signature on the final sonic outcome that changes of equipment and cabling upstream only slightly affect the results. Not the Gen. IIs! Every change of component in front of them is highlighted and easily noted. And though the VRs were seriously influenced by all components upstream, the complicated amplifier/speaker interface seemed the most influential. Contributing a fairly easy load by providing a highly stable impedance and coming in at 91dB efficiency, these speakers should be capably driven by any but the smallest of triode-powered micro amplifiers. Rumor has it that a good part of the final voicing of the VRs is done with the Pass Labs Aleph 2 monoblocks. That gave me great hope for the pairing with my Pass Labs Aleph 3, a match-up which evoked absolute magic! My Clayton S-40, though a lush match in the mids, just didnt exhibit the control at the bottom or the extension at both extremes that the robust little 3 could muster. And though all entrants from my Hafler stable tended to work adequately, they all showed their overall hardness and that typical class-A/B glare from the upper mids on up. Careful choice of amplifier pairing will benefit the owner in ways well worth the time and expense involved in that quest. Contributing to that crucial amp/speaker interface, the Gen. IIs proved to be very sensitive to loudspeaker cable matching. I tried a plethora of cables and found myself coming back to the JPS Labs Superconductor biwires as the best overall performer in my listening. Close seconds included the Goertz Alpha Core MI-2 and AG-1. With the exception of the rolled-off bass performance of the otherwise sweet-sounding AG-1, they were very magical. But the loss of both that vivid sense of space of the sound stage and the incredulous slam these speakers can deliver was just too much to overshadow the glory of the mids and highs. The MI-2, though capable of restoring that lost space and weight, just werent quite as luxuriant and correct through the upper mids and highs as the JPS entrants, which brought the whole game to the table in spades. Disappointing performance from the likes of Tara, Straightwire, MIT and DH Labs conspired to convince me yet again of the consummate significance of this crucial union. The Zen koan Steeped in rich heritage and hoary tradition, the Zen Buddhist master uses many tools to help the aspiring student acquire knowledge in his quest for such. Among the tools of the Rinzai sect is a purposeful riddle, often in the form of a simple question, known as a koan. The purpose of the koan is not so much to teach in the active sense, as it is to impel the novitiate to think for himself and thereby come to understanding of his own accord. Zen suggests, as do all good teachings, that a lesson is better learned if self-discovered rather than externally imposed. The unique thing about the koan is that there is no one right answer. As a matter of fact, the answer itself, once divined by the practitioner, isnt nearly as important as the self-understanding that accompanies the process of answering. The purpose of the koan is to spur the development of a level of understanding that transcends the need for asking the question. The koan is an instrument to allow one to find truth. Thus I find the newest prodigal son from the Virtual Reality series of loudspeakers by Albert Von Schweikert. In the presence of the VR-4 Gen. II, the understanding of the music becomes intuitive. The VR-4 assumes the job of the koan, placing the music as Buddha and allowing you, the listener, to assume the role of Kashyapa. The understanding comes directly and without effort. They are an instrument for divining truth. Just as Kashyapa understood Buddha without effort--directly--you are permitted understanding at the voice of the Von Schweikert Research VR-4 Generation II. They break through the need for reason and allow purpose. Music through them transcends the mechanism of reproduction, allowing the listener to hear past the medium and back to the true message of the music. They function as time machines, providing the most direct path back to the musical event Ive ever had in my Such crystalline clarity, vivid detail, articulate and extended bass, equality of balance, realism of presentation and emotional involvement have never been more successfully integrated into one more attractive and affordable package in my near 30 years of searching. The VR-4 Generation II may well be the first true landmark or milestone product Ive had the pleasure of reviewing over the last decade. This speakers ability to completely get out of its own way and resurrect only the recorded performance is unrivaled in this extremely competitive price range, finally bringing previously unbelievable levels of performance below the $4000 mark. It, in fact, bests some well-known entrants from some very respected manufacturers selling for nearly twice as much. I still find it next to impossible to give over to the music and do anything else when my system is playing with the alluring Von Schweikert VR-4 Generation IIs. From me, there is no higher recommendation. |Von Schweikert Research VR-4 Generation 2 Price: $3,950 USD 800 Starbuck Ave. Watertown, New York 13601

- Part 1 – Overview - Part 2 – the Label - Part 3 – the Source Code - Part 4 – the Partial View - Part 5 – the Required Field Indicator The Required Field Indicator The Required Field Indicator is a property which allows the UI to indicate that a field is required. The example below shows that an asterisk could be used to indicated the field is required. This could be used to apply a css class to the Label which could change the color or bold the label. The possibilities for how you turn this property into a compelling user interface is endless. The important point to know is that there are different approaches to decide how this could be set. Here is an example of using a DataAnnotations Required attribute as a way to indicate the field is required. I like this approach since this attribute can be used with a Model Binder to perform Model Validation using model state. This model binder will be provided in the ASP.Net MVC 2.0 release so I included this as a way to get synergy with existing features of the MVC framework. I have received a lot of feed back that people feel marking your model with attributes pollutes the model. I disagree with this because the models that I use are View Models not my Domain entities which represent my business object which will be stored into my database. The Models that I would decorate with validation attributes would be used for one specific MVC View. The model would represent the fields needed to create the User Interface view. An alternative approach to using attributes would be to use a Fluent method as shown below. I dislike this approach as it does not work with my preferred way of performing data type validation using the MVC Model Binder. in the framework. I would be more likely to use the fluent methods for the Label or PartialView selection, but I would not use it for the Required indicator because it would mean I am duplicating how I identify a required property on my Model. The View markup Here is an example of how the Required property is used in the Field.Master master page. As I wrote earlier, this could be used to add a css class to the html markup. Your own convention The framework uses a convention to determine if a Model property is required. By implementing your own PropertyIsRequiredConvention you could make all Properties with the name Name & Description required or whatever makes sense for the type of application that you are creating. It could be Username or email if you are creating a consumer facing website the possibilities are endless. But at the end of the day you can have your own convention. Here is the implementation of my Default Convention for Property Is Required, it is simple and to the point. I could see implementing some sort of Chain of Responsibility pattern here and in the other conventions to have some consistency to your User Interface.

I have just started using this tool - I am very impressed. I had previously written my own tool that was built on top of Telelogic Synergy and wanted a review tool when a change in employer resulted in a change in SCM system (SVN) I have a number of questions: 1. Is there anyone who can help me with the necessary changes to get a column added to the dashboard that shows the total number of people asked to do a review. Without this its very hard to know if X/Y people have marked ship it. 2. As a developer I want as much stuff as possible to be automated. Does anyone else see any value in getting review board to post the changes to the repository? What I mean is that the users all review the code and then the author changes the status to 'submitted' - at this point review board could apply the patches or change set to the repository. If this works great, if it does not inform the user that further rework is required. I have no idea how hard this would be! But it means that developers write code, get it reviewed, mark review as complete and changes are posted. Otherwise these is that danger period where you get code reviewed, every one accepts and you then try to commit and fail. Great tool, and I have high hopes of rolling this out to other developers and teams! Want to help the Review Board project? Donate today at Happy user? Let us know at http://www.reviewboard.org/users/ To unsubscribe from this group, send email to For more options, visit this group at

Meeru Dhalwala, Shanik Restaurant | BCBusiness After delays and a flurry of anticipation, Dhalwala's Seattle restaurant, Shanik, finally opens. Meeru Dhalwala, the co-owner and chef of legendary Vancouver Indian restaurant Vij’s, is invading the U.S. via Seattle. But is her long-awaited Shanik restaurant the ingredient that begins to tie Cascadia together? On the first Monday of December, an anxious sigh broke through Seattle’s Twittersphere as rumours circulated that the opening of Meeru Dhalwala’s Shanik restaurant would be delayed by 48 hours. Shanik had topped Eater.com’s national list of “Most Anticipated Bar & Restaurant Openings of Fall 2012.” The most-viewed story on city magazine Seattle Met’s site that week read: “We’ve waited. And waited. And salivated. Now the Vij’s Seattle sibling is finally here. This. Is. Happening.” By 9 p.m. on its first official night of operation, Shanik was winding down. Inside, the song “Mykonos” by local band Fleet Foxes hung in the air and there was no hint of the pre-opening buzz. Yes, there were signs that the Vancouver gastronomic phenomenon had arrived: Dhalwala’s signature “wine-marinated lamb popsicles in fenugreek cream curry on turmeric and spinach potatoes” had become “spice-encrusted lamb popsicles with coconut curry and split peas, spinach and garlic mash,” and there were some familiar faces from the all-female kitchen back home on South Granville. But it was all a bit out of place on a glassy corner in South Lake Union, across the street from Amazon.com Inc.’s world HQ. It’s the sort of corner where you’d expect to find the new Cactus Club. It’s a Yaletown kind of corner. “In a way, Seattle chose me,” Dhalwala says. “Oguz Istif is COO for Vij’s [Restaurant Inc.] in Vancouver. For the past few years, he and I have joked and talked about opening a restaurant together in Istanbul. I was approached to visit Seattle and meet with various developers interested in a Meeru-run restaurant. So, Oguz and I decided that Seattle would be a good trial for Istanbul! Seattle is close enough that we can run a restaurant there while being able to spend time with our families in Vancouver.” She adds that Vij is planning to open a restaurant in White Rock and the flagship location on Cambie this year. “All of our restaurants informally, emotionally are part of the Vij’s mother ship. Even if they are independently owned,” she says. “She wanted to do something on her own, so this is her venture,” says her husband and business partner Vikram Vij, adding that the couple still considers the Seattle restaurant as falling under the Vij’s/Rangoli umbrella. “We are both ready for side, independent projects,” says Dhalwala. “I want to get out on the floor and interact with customers and do more marketing work, whereas Vikram would like to get back into the kitchen more.” Ten years ago, Mark Bittman travelled to Vancouver and wrote the New York Times review of Vij’s that put Dhalwala and her husband on the world map. Bittman wrote that the experience was uniquely Vancouver, but paradoxically regional at the same time. Vij was the classically trained chef; Dhalwala eschewed culinary school for a master’s in development studies and an assignment in Rwanda. They brashly mixed spices from Gujurat with spices from Punjab. Bittman referred to the restaurant’s aloo paratha as “a paradigm.” And then he wrote the line – the glorious line that would ensure a two-hour lineup every night for the next 10 years – “easily among the finest Indian restaurants in the world.” It would be repeated again and again. Sometimes the word “among” would slip out of the sentence, the “s” off “restaurants.” But the aloo paratha paradigm was nothing. One year later, Vij and Dhalwala opened a second restaurant, Rangoli, next door. Dhalwala, who likes to anthropomorphize her businesses, likened Rangoli to the wilder younger sibling of the original Vij’s restaurant. Rangoli’s paratha was made with spiced, roasted and ground crickets. The couple worked with a specialist in edible insects from Seattle to source the crickets. “Customers were both shocked and curious about our decision to put crickets on the menu,” she explains. “Vikram thoroughly enjoyed the look on their faces.” Raised in Washington, D.C., Dhalwala was introduced to Vij just after he opened up a 14-seat restaurant on West Broadway. “It was easier for me to move to Vancouver, since I could look for a job anywhere. I was so head over heels in love that I would have moved into a slum with stray dogs and cats.” If you don’t count Daniel and Henrik, Dhalwala and Vij are arguably the closest Vancouver comes to royalty: they are the faces of a city and represent a way of business that both transcends and defines physical location. The popular frozen food counter at Rangoli became a 28,000-square-foot production facility in South Surrey, pumping out a line of 15 different 300-gram flash-frozen products sold in more than 100 grocery stores. They published two best-selling books, launched a high-end downtown food cart, built a $250,000 culinary lab at UBC and organize the annual Joy of Feeding celebration of ethnic home cooking. Years after Dhalwala literally put ground crickets on Vancouver tongues, the potential of insects as food in the Western hemisphere has become an intelligent conversation in the popular media. Of course, Seattle is not exactly a culinary backwater itself. New Times food critic Frank Bruni recently declared that he was “hard-pressed to think of another [city] where the locavore sensibilities of the moment are on such florid (and often sweetly funny) display.” And true to form, Shanik’s mission statement promises “foremost attention to locally sourced, seasonal produce; sustainable seafood and clean, medication-free meats.” But it’s too easy to mistake Shanik for the missing South Asian piece of the jigsaw puzzle that is the Seattle food scene. Maybe what’s really driving the interest is an awakening to Vancouver as a kind of long-lost cousin – there’s a deeper Canadian literacy in Seattle than in most other American cities. At a dive bar near Pioneer Square, the manager grilled me about which B.C. craft beers he should pour. At Revel, a restaurant in Fremont – the Korean equivalent of Vij’s – a cook, already well-versed with Dhalwala’s craft, wanted to know about restaurants like Maenam and Phnom Penh. Less than a dozen blocks from Shanik, Burnaby developer Nat Bosa has just broken ground on the first of two 41-storey condo towers, the first new Seattle condo project in five years. And when shows like The Killing mash grim angles of the Emerald City skyline with the fine grain of Vancouver’s back streets, the cumulative effect is that the two blur in your imagination like a pair of hand-crafted wet wool socks. Add in a friendly Whitecaps and Sounders rivalry and you have a strong cultural synergy between two cities on the physical and psychological edge of their respective countries. This 72-seat dining room, 40-seat lounge and takeout counter across the street from the biggest online retailer the world has ever known might be the ingredient that begins to really tie Cascadia together.

Welcome to the home of King of Shaves The World's Best Shave! For 15 years we have been supplying our fantastically smooth shaving oil and gel 'software' and now we are proud to present the new King of Shaves Azor Hybrid Synergy System Razor that 'shaves closer, longer for less!' Here you will also find shaving tips (no razor burn, razor rash or 'chicken neck' with King of Shaves shaving software and Azor hardware), the opportunity to sign up for our email updates, competitions and more Is Azor your business? Claim your listing and attract more leads by adding more content, photos and other business details. We have more Skincare services available on Hotfrog NewZealand. You can update your search for Skincare by location, keyword or service options.

Meet the Cool Satellites That NASA Will Send Into Space For the past six years, NASA has been building a new launch apparatus designed to once again take us beyond Earth’s orbit, to Mars, and beyond. And in just a little more than two years, the Space Launch System will embark on its inaugural launch and separate from the Orion spacecraft, which will circle the moon and eventually return to Earth. Accompanying Orion on that 2018 mission will be 13 small objects known as CubeSats, which illustrate what the future of space exploration and research will be: efficient, cost-effective, and taking advantage of the most innovative science and technology breakthroughs to date. NASA has finally revealed what kinds of CubeSats are hitching a ride with Orion and heading off into deep space, and they look pretty fantastic. They represent, in the words of NASA deputy administrator Dava Newman at today’s announcement, “the synergy of where we can do science and technology.” To review: CubeSats are basically cheap, miniature satellites that are basically as big as a shoebox, and can act as a type of multipurpose tool for all kinds of projects. The first CubeSats were launched in 2003, but they’ve exploded in popularity starting this decade, thanks to NASA’s CubeSat Launch Initiative that provides opportunities for students and research teams from around the world to send CubeSats to the International Space Station. Until now, CubeSats have primarily been used for educational purposes, according to Michael Seablom, chief technologist for NASA’s Science Mission Directorate. Even when they’ve been used as a part of scientific research, it has been in a pedestrian manner that’s non-essential to the study at large. Seablom and others hope to change that very soon. The SLS-Orion integrated launch — set for September 2018 — is a —> Read More

A word about the Club's associated sponsors and partners Marcus Evans is one of the world's leading providers and promoters of global summits, strategic conferences, professional training, in-Company training, business-to-business congresses, sports hospitality and online information. Founded in 1983, the company now employs over 3,500 employees operating into 36 countries around the world. The company's revenues are generated from clients from the majority of the world's top 1,000 companies. An international network of offices provides a one-stop shop for a company's business intelligence, learning and training needs. The company maintains the highest standards of quality and service in research, technology and product development. The company's commitment to service and quality are the basis for their reputation as the world's leading provider of business intelligence. Ipswich Town Football Club's organisation and winning team parallel the ambitions and achievements of Marcus Evans, and this long-term association will provide excellent opportunities for both the Club and the Group. The values of ITFC demonstrate a clear synergy between the values of the Group and those upon which the Club have been built: success, performance, ambition, competition, endeavour, achievement, excellence, reward, leadership, innovation, tenacity and teamwork. A further benefit for the Group will be to access the experience of a winning football management team and their knowledge of motivation and team building. As an enterprise the Group will provide ITFC with the long term stability, investment and resources of a successful global company, as well as helping to provide the basis of a global scouting structure. Through this partnership the aim is to return Ipswich Town Football Club, already one of England's most respected and admired clubs, into the top level of English Football, engage our clients and employees with the excitement associated with the greatest sport on earth, and bring unprecedented awareness of the Marcus Evans brand as the world's leading business information and hospitality company. For more information visit www.marcusevans.com. Ipswich Town and adidas (UK) Ltd announced a four-year deal in July 2014, to see the sportswear giant become the Club's official technical kit supply partner. The partnership means adidas (UK) Ltd will produce the kit from first-team level through to the Academy, as well as covering training and replica kit. The agreement, which includes the Club shop, Planet Blue, receiving a makeover, sees Town and adidas working together for the first time in 25 years, with the fdamous three stripes emblazoned on a Blues' shirt during the Club's heyday when the FA Cup and UEFA Cup trophies were held aloft at Portman Road. For more information, visit www.adidas.co.uk East of England Co-operative The East of England Co-operative are the sponsors of the West Stand at Portman Road. The East of England Co-operative Society is the largest independent retailer in East Anglia and has over 200 trading outlets which are located in more than 70 towns and villages. Employing around 4,700 people, the Society also has over half a million members. The Society's business included food stores, pharmacy, travel, electrical, optical and funeral services. Visitwww.eastofengland.coopfor more information. Greene King IPA Town announced a five-year sponsorship deal with Greene King IPA in July 2014, which will see the Bury St Edmunds based brewers hold the official pouring rights at Portman Road. The company, who sponsored the Club shirts the season Town won promotion to the Premier League via a Play-Off final win over Barnsley, will also sponsor the Sir Alf Ramsey Stand. As part of the partnership, the two 'book end bars' found in the Sir Bobby Robson Stand have been renamed the 78 and 81 bars. A multi-service facilities management provider in East Anglia; Vertas Group Limited, signed a three-year partnership deal with the Club in Summer 2016. Vertas partners with clients at over 400 sites in Suffolk, Norfolk, Essex and Cambridgeshire; providing services such as catering, cleaning, grounds design and maintenance, energy management and much more. Both the Vertas Group and ITFC saw many similarities in the ways which the businesses are run; both organisations lead their business dealings with a strong focus on staff and customers; demonstrating key values such as agility, sustainability and consistency. With the Vertas Group’s considerable experience in public and private sector service delivery and its far ranging portfolio of small and large business clients across East Anglia, alongside the well-loved and trusted ITFC brand it was a key opportunity for both businesses to find ways of working closer together. The partnership involves many opportunities for both the Club and Vertas Group to mutually work together for the benefit of the wider community, some of which include: ITFC nutritionist’s support in creating healthy, ITFC endorsed menus for the Vertas Group catering provided in schools Ongoing advertising, promotion in programmes, on the pitch throughout games in the upcoming season and events and joint activities in schools Cross-service improvements, key learning from each other in excellent service delivery and customer satisfaction Find out more about the Vertas Group at www.vertas.co.uk or follow them on Twitter @VertasFM TeamCard is the UK's largest and most widely recognised sports membership programme. The essence of the business is to provide key solutions that will engage a target audience, record all transactions and reward those transactions to create compelling retention strategies. In addition to being a loyalty card for season ticket holders and Club members, TeamCard is also a match day stadium access system for season ticket holders.

LEASED BY WARREN MARGETSON |1 | 2 | 3 | 4 | 5 | Next >>||1 of 5| 5/24 Duntroon Street, Hurlstone Park, NSW 2193 2 Bed | 1 Bath | 1 Car Property ID: NSW11068529 Ideally located close to all amenities, this first floor apartment is an ideal and affordable rental opportunity. Within walking distance of the newly completed Inner West Light Rail Extension, eclectic cafes, shops and buses, this breezy, sun-drenched 2 bedroom apartment is also close to great schools and parks. Situated at the rear of the block, this quiet oasis is without fault, boasting a modern kitchen and bathroom as well as spacious living area. View CENTURY 21 Synergy PH: 02 8507 8070 Mobile: 0411 340 005 Email: Email Me

Japan applies new technologies for replacing and uprating extra-high-voltage cable circuits. In Japan, electric utilities have installed underground cables on transmission systems up to 500 kV to supply electric power to urban areas. Construction of these underground cables connecting power plants and urban or suburban areas took a long time to complete. However, older power plants have been replaced, making it necessary to increase the capacity of existing circuits or replace the aged cables. The majority of underground cables in Japan are installed in ducts and tunnels. One advantage of this installation method is cable can be installed on an as-needed basis because additional civil engineering work does not have to be performed simultaneously. Conversely, if the required number of circuits needed exceeds the design number of available ducts or tunnels, new underground facilities have to be built, which is a challenging issue in urban areas because of the vast capital cost and construction time required. Japanese utilities have taken advantage of recent developments in innovative technologies for increasing transmission capacity and replacing cable, which has contributed to the completion of many extra-high-voltage (EHV) cable projects in which existing ducts and tunnels could be used. One of the largest cable construction projects ever undertaken in Japan is a cable capacity enhancement project using existing tunnel space. This project followed the replacement of a thermal power plant and the inevitable increase in generating capacity. A total of 20 circuits, involving the installation of 111 km (69 miles) of 154-kV cable and eight circuits with the installation of 13 km (8.1 miles) of 66-kV cables, were installed. Some 201 km (125 miles) of time-expired cables were removed during this capacity-enhancement project. The largest challenge was to install four 154-kV cable circuits in an existing tunnel that already housed three 154-kV cable circuits. Typically, an additional 3 km (1.9 miles) of tunnel would have been required, but the use of triplex cable avoided normal measures to accommodate cable thermal expansion and contraction, often referred to as snaking. Normally in Japan, a single-core cross-linked polyethylene (XLPE)-insulated cable would have been used for 154-kV cable circuits. Installing single-core cables in a tunnel requires design for cable snaking at a predetermined pitch and width as a countermeasure against cable thermal expansion and contraction. However, with the triplex cable, such expansion is absorbed by change in the triplex cable diameter. This twisted flexure saves expansion space and allows for more efficient use of the underground space from a 2-D perspective. There are other efficiency advantages between single-core and triplex cables: Reduction in cable installation work and a significant reduction in accessories such as cleats, cable supports and other hardware Reduction in space required in the cable joint pits and inside the manhole sections Reduction in the space required for cable drums. The change in design practice to using triplex cable avoided the construction of a new tunnel, reducing the project time period and overall expenditure. The electrical performance of the XLPE-insulated triplex cable was considered adequate given its basic structure is identical to the XLPE-insulated single-core cable. Still, cable-bending mechanical and thermal behavior verification tests were conducted during triplex cable development, including an application evaluation. Previously, the XLPE-insulated triplex cables were used for specifications up to 66 kV and 600-sq mm (0.93-sq inch) circular compact-stranded wire copper conductors. For this 154-kV project, the triplex cable had 1,000-sq mm (1.55-sq inch) segmental copper conductors. Verification was required to ensure the conductors were not affected by cable bending, and the thermal expansion and contraction were absorbed by means of diametric expansion. The triplex cable occupies less space than conventional cable, which was a huge savings on civil engineering costs. This project was completed on schedule in December 2008. Existing Cable Use A plant replacement project led to the construction of new 275-kV cables to supply an inner-city area. However, to avoid replacing the cable circuits, the transmission system was reinforced with additional 275-kV cables. For this project, three circuits were installed that involved 18 km (11 miles) of 275-kV cable to allow for a 1,500-MW increase in generation capacity. A new 275-kV Y-branch joint was developed to enable connection between the new solid dielectric cable and the existing self-contained oil-filled (SCOF) single cables. To achieve synergy in the usage of XLPE-insulated and SCOF cables, an insulation component made of epoxy was designed as the primary insulating body. On the XLPE side of the joint, a premolded insulator and prefabricated straight joint were used. This resulted in a composite structure that uses a compression ring (spring unit) to apply appropriate pressure at the boundary between the cable and the epoxy insulator. The oil-filled cable side used an insulated oil-impregnated paper and the epoxy bell mouth, resulting in a structure that allows for dimensional compatibility between the premolded insulator on the XLPE side and the inner dimensions of the epoxy insulator. The contact surfaces of the ferrule and embedded electrode are silver-coated. It was experimentally confirmed that no corrosion arises at the contact of the two metals, even if the silver coating is damaged. The electrical performance of the joint satisfied the Japanese Electrotechnical Committee Standards. Although a forced water-cooling cable system was installed, the installation of a new cooling station appeared necessary to satisfy the increased load-transfer capacity of the circuits. However, the proposal to install a new cooling station was deemed practically impossible due to cost and finding a suitable location. As an alternative measure, a cooling booster pump was developed to enable the hydraulic circuit length of the chilled water to be extended and to increase the cooling capacity. It has been confirmed elevation differences within the water-transfer route do not lead to any booster pump operational problems. Furthermore, verification tests on the water-transfer system did not reveal any significant design problems. Construction of the XLPE cable installation was completed in June 2007. The cooling-water upgrade was finished in June 2009. A 275-kV SCOF cable with joints positioned on an incline was subject to repeated movement between the core insulation and outer aluminum sheath. As a permanent solution, the existing cable was replaced with a 275-kV XLPE-insulated cable. When replacing cables, the new cables are generally installed in the space vacated by the removal of the existing cable. However, this was not possible without a lengthy circuit outage, so this solution could not be adopted. Therefore, the replacement 275-kV cable was installed on a different route in an existing cable tunnel. The new 275-kV XLPE-insulated cable was designed with a laminated aluminum water-shield layer, and it was necessary to install a Y-branch joint for this XLPE-insulated cable. Installation required a long cable pull in the tunnel. The resolution to both of these construction issues reduced the project cost and circuit outage time. Transmission system operators in Japan acknowledge the workload associated with the uprating and upgrading of existing cable systems, necessitated by increased system demand and future plant replacements, will increase. Although new construction technologies are available, they are becoming more difficult to implement due to the lack of underground space. Furthermore, there is a general problem of securing equipment and construction space in densely populated urban areas. Japanese utilities have developed and implemented many new technologies — such as triplex cables, Y-branch joints and laminated aluminum water-shield layers — to increase the effective use of existing system assets. These new technologies will help meet the challenges posed by current social demands for electric energy, and there is considerable optimism regarding their future and diverse applications. The authors express their gratitude to S. Katakai of J-Power Systems Corp., T. Nakajima of VISCAS Corp. and M. Owashi of Exsym Corp. for their help and support in preparing this article. Shinichi Tsuchiya (email@example.com) received BSEE and MSEE degrees from Tohoku University, Japan. He has been engaged in all technical matters concerning the design, construction and maintenance of underground transmission with the Underground Transmission Group of Tokyo Electric Power Co. Tomohiro Kiguchi (firstname.lastname@example.org) received BSEE and MSEE degrees from Yamanashi University, Japan. He has been engaged in all technical matters concerning design, construction and maintenance of underground transmission lines in the Underground Transmission Group of Tokyo Electric Power Co. Makoto Nishiuchi (email@example.com) received BSEE and MSEE degrees from Osaka University, Japan. He has been engaged in the design, development, construction and maintenance of underground transmission lines and submarine cables. Currently, Nishiuchi is the director of the district office responsible for the maintenance of power equipment at Kansai Electric Power Co. |Electrical properties||Long-term performance||AC 230 kV for six months| |Initial performance||XLPE||AC 525 kV for one hour Imp ±1,455 kV × 3 shots (AT)| |SCOF||AC 350 kV for three hours Imp -1,260 kV × 3 shots (AT)| |Partial discharge||Less than 5 pC at 300 kV| |Dimensions||Height × width × length of ≤500 mm × ≤950 mm × ≤2,500 mm (≤19.6 inches × ≤37.4 inches × ≤98.4 inches)| |Cable||XLPE||Conductor size up to 2,500 sq mm (3.9 sq inches), Insulation thickness of 23/27 mm (0.9/1.1 inches)| |SCOF||Conductor size up to 2,000 sq mm (3.1 sq inches)| |* Based on Japanese Electrotechnical Committee Standards 3401 (1986) and 3408 (1997).|

This game exposes our thoughts on changing and our acceptance to change. Effective change requires open mind and technical competence. Break into groups of two and allow each other to get to know each other for a couple minutes. Have one person turn around and have the other person change five things on them, such as take off glasses, add a pen to shift pocket, etc. When five items are changed ask your partner to turn around and identify as many of the changes as possible. Now alternate roles and do the same. Do this for 4-5 cycles without repeating the same changed item (for example you can only take off your glasses one time). How many people started floundering for ideas in early rounds? How many people started looking around the room for supporting ideas? How many made the easiest changes first? What innovative ideas were there? Did you find that the more you changed the more difficult it became to change? Make up a list of famous names, one name written on one sticker label. Stick one famous name on the back of each participant. The rules are that the participant can ask each person in the room one question that can be answered by either a "yes" or a "no.” Example: "Is this famous person a male or female?" After the participant receives the answer, he or she must move on and ask another person the next question. The person that guesses his or her "identity" with the fewest questions gets a prize. Are you Alert? This is a fun and quick activity to stress the importance of being alert and observant. Before the meeting, prepare a tray of at least 25 items and cover the tray. Participants will have one minute to look at the objects on a tray before covering it again. It is best to keep everyone seated and position the items so they can be viewed by everyone from their seats. They will then be asked to write down as many things as they can remember. Ask for volunteers to read their list. Award a prize for the person who remembers the most items. Place a variety of objects placed in a bag. Have each person pull out an object from a bag and explain how they are similar to it. Pass the bag on to the next person, you can put the objects back after each turn or leave them out. This obviously leaves those later in line with fewer things to pick from. You can also have them select from the bag without looking, this would require giving that person a few seconds to come up with a response and can be more nerve wrecking. Or the team facilitator can hand out an object to each person, then give each person a few minutes to think about how they are similar to the their object and then go around and let each person voice their response. This activity allows the development of synergy, no one person is as smart as everyone combined. First, ask individuals to write down the keyboard of a standard typewriter from memory. Then allow groups of four to compare keyboards. When individuals or groups feel they have the perfect keyboard, they should turn their paper over and wait patiently. If the group of four is not certain they are correct, they can merge with another group, and so on. Display a typewriter keyboard for them to check their answers. Draw the conclusion that we must share information and work together to be the most effective as a group. This warm-up is related to the warm-up "WHAT ARE YOUR VALUES?” An alternative to having the participants discuss their top three values is to have an auction of the values. Explain that they are being given an opportunity of a lifetime. They are going to be given $10,000 to spend on an auction of the values they rated in the activity "WHAT ARE YOUR VALUES?” Before beginning the auction, record the names of all participants on a flip chart or chalkboard. As each value is sold, record the price and the value next to the participant's name. Be sure to keep a running total amount spent for each participant so that no one spends beyond the $10,000 limit. Here is an example of how the auction is started: "Okay let's begin. Who would like to buy a comfortable life, full of prosperity and all the good things life has to offer?” Continue auctioning the rest of the values. In a large group, discuss which value has the most importance for your group and why. Whenever possible, relate to work and/or the purpose of the meeting. Provide a list of criteria for each participant to seek from their peers. Instruct them to walk around the room and try to find someone in this group who matches as many of the questions as possible. The same person may be used for more than one question. 1. Someone with the same color eyes. 2. Someone born in the same city, state, or country. 3. Someone who has the same astrological sign. 4. Someone who likes the same sport. 5. Someone who has the same favorite dessert. 6. Someone who is the youngest of the family. 7. Someone who would like to write a book. 8. Someone who has seen the same movie at least three times. 9. Someone who has lived abroad. 10. Someone who likes to ski. 11. Someone who is an only child. 12. Someone who can speak two languages. 13. Someone who likes to cook. Have everyone record and announce the number of questions that they received answers to within five minutes. Offer a prize for the person who found the most similarities. Two Truths and a Lie The object of the Game is to guess which of the three "facts" is the lie to get the group members to know each other. There are no items or preparation required other than a few minutes for each person to come up with two truthful statements and one lie about themselves. Example: The three things one person could say are “I enjoy skydiving”, “I can speak three languages fluently”, and “I am an only child." The others try to guess the lie and once everyone has made their choice the lie is revealed. Those that were correct get a point and so on. The person with the most points could be awarded a prize. Break into groups of no larger than five people. Discuss the top five items you would have brought with you if you knew there was a chance that you might be stranded on a deserted island. Note that they are only allowed five items per team, not per person. Have each group discuss their response with an elected spokesperson. This activity helps them to learn about other's values and problem solving styles and promotes teamwork. Divide the group into teams of 3-4 people. Give each team the same diagram for building a skyscraper with a deck of cards. The team that can build the highest structure in five minutes wins a prize. The goal of this activity is to enhance teamwork or to create positive interaction between the members of a hostile group. Divide into teams of four people and assign one champion and one recorder. The object of this warm-up is to recognize the need to plan and observe how others make and implement their plans. Inform the subgroups that they are planning a trip from Boston to New York City. The following conditions apply: 1. It is a weekend trip (three days). 2. There is a family of five. 3. Budget is limited to $500. 4. There is a working car. Taking the above factors into consideration, plan a trip. After six minutes, ask for group reports. Discuss the importance of planning the differences between the groups. Six Sigma Modules The following presentations are available to download Green Belt Program 1,000+ Slides Cause & Effect Matrix Central Limit Theorem 1-Way Anova Test Correlation and Regression Six Sigma & Lean Courses

Co.Create associate editor KC Ifeanyi stopped by Sesame Street recently to get a new perspective on corporate jargon from everyone's favorite Muppets. The 46th season of Sesame Street will premiere Saturday, January 16th for the first time on HBO. Watch Elmo And The "Sesame Street" Cast Turn Corporate Jargon Cute What does "synergy" really mean, anyway? Your guess is as good as Elmo's.

This boar bristle and nylon mix brush is best for normal to thick hair, with 8 rings of pure bristle and nylon tufts to stimulate blood flow to the hair roots. The density of the bristles allows conditioning sebum to be more evenly distributed from the roots to the ends of the hair.Regular brushing plays an important part in the condition of your hair. Brushing spreads essential oils along the How many dragons do you know? We bet you dont know any like Marmaduke. Hes different and thats how he likes it. In his kingdom, most people and dragons are (whisper it) a bit boring. But Marmaduke will always surprise you! So its no wonder that this sparkly dragon is very popular. Other dragons, princesses, princes and knights all want to be his friend. Its great! But one person isnt quite so Sturdy GPS mount made from 6061 aluminium Features a plastic insert which is kinder to the base of your GPS unit than CNC'd types Suitable for 31.8mm handlebars Anodised black for long lasting finish Average weight 46 grams Keep your music close with a heavy-duty tripod microphone and music note stand from Pyle. This music stand features adjustable height leveling, a long lasting steel construction, and folds compactly for convenient transport. Adjustable height leveling Microphone boom with mic holder Long-lasting steel construction Folds compactly for convenient transport and storage Desk Keep your look popping in the Popular heels from Isaac Mizrahi New York!Leather upper.Ankle strap with buckle closure.Open-toe silhouette.Metallic accent.Synthetic lining.Padded footbed.Wrapped heel.Synthetic sole.Imported. Measurements:Heel Height: 3 1 4 inWeight: 6 ozProduct measurements were taken using size 5.5, width B - Medium. Please note that measurements may vary by size. Relax and unwind with this works Sleep Tight Gift Set. Combining three aromatherapeutic solutions for a good nights sleep, the pillow sprays and fragrant roller ball work in synergy to inspire feelings of calm and prepare you for a deep and restful slumber. The Set Contains: deep sleep pillow spray (5ml): A best-selling natural sleep aid that inspires feelings of calm. Designed to inspire a Pet Works Holiday 10\ Cotton Rope comes with two ten-inch braided ropes in Christmas colors that make perfect stocking stuffers for your dog. Pet Works Holiday Cotton Ropes are braided for high durability so that your dog can be chewing them long after the lights are down and the tree is on the curb. These braided ropes make for great fun whether youre tossing them for a game of fetch or

- About this Journal · - Abstracting and Indexing · - Aims and Scope · - Annual Issues · - Article Processing Charges · - Articles in Press · - Author Guidelines · - Bibliographic Information · - Citations to this Journal · - Contact Information · - Editorial Board · - Editorial Workflow · - Free eTOC Alerts · - Publication Ethics · - Reviewers Acknowledgment · - Submit a Manuscript · - Subscription Information · - Table of Contents Journal of Biomedicine and Biotechnology Volume 2010 (2010), Article ID 130265, 6 pages Monocyte Chemoattractant Protein-1 2518 A/G Single Nucleotide Polymorphism Might Be Associated with Renal Disease and Thrombocytopenia of SLE 1Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781 Poznań, Poland 2Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland 3Institute of Rheumatology, Warsaw, Poland 4Department of Radiotherapy and Gynecological Oncology, Greater Poland Cancer Centre, 15 Garbary St., 61-866 Poznan, Poland Received 30 November 2009; Revised 13 February 2010; Accepted 14 March 2010 Academic Editor: Timothy B. Niewold Copyright © 2010 Piotr Piotrowski et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. There is conflicting evidence on the contribution of the MCP-1 −2518 A>G (rs 1024611) polymorphism to SLE incidence and clinical manifestations. We examined the prevalence of the MCP-1 −2518 A>G polymorphism in SLE patients () and controls () in Poland. We did not observe a significant difference in the distribution of MCP-1 −2518 A>G polymorphic variants in patients with SLE and healthy individuals. However, we found an association between the GG versus AG and AA genotypes as well as the AG and GG versus AA genotypes with renal manifestations of SLE (1.123–11.631, ) and (1.301–4.057, ), respectively. We also observed that the MCP-1 AG and GG -genotypes contribute to the occurrence of thrombocytopenia in SLE patients (1.280–5.352, ). Our observations indicate that either MCP-1 −2518 G variant can be associated with some clinical findings in patients with SLE. Systemic lupus erythematosus (SLE) is a chronic and progressive multisystem autoimmune connective tissue disorder, which is characterized by immune-mediated host tissue destruction . Occupational exposure, chemicals, drugs, food, as well as viral and bacterial infectious agents can contribute significantly to changes in the immune system [2, 3]. Immune cells from patients with SLE exhibit various defects including skewed cytokine production, a decrease in cytotoxic T cell function, and an increase in the humoral response [4–7]. The defective function of CD4+ T cells associated with abnormal stimulation of B cells causes abundant autoantibody production [4, 6]. These autoantibodies form immune complexes with antigens on the patient’s own cells and are accumulated in the skin, synovium, lungs, renal glomeruli, and other organs and tissues. This results in the clinical presentation of SLE [1, 8]. The pathogenesis of SLE remains unclear, though there is much evidence demonstrating the involvement of genetic factors in the incidence of this autoimmune disease [9–13]. The genetic background contributing to SLE development includes, in particular, genes encoding disparate proteins that control immune system pathways [9, 10, 13]. The monocyte chemoattractant protein 1 (MCP-1), currently also designated CCL2, belongs to the family of chemotactic cytokines. MCP-1 functions as a potent agonist for monocytes, memory T cells, and basophils . Evidence in animal and human studies suggests a significant role of MCP-1 in the progression of glomerular and tubulointerstitial injuries and glomerulonephriti in patients with SLE [15–19]. It has been demonstrated that the MCP-1 –2518 A>G (rs 1024611) transition in the promoter region may modulate the levels of MCP-1 expression [20, 21]. The MCP-1 –2518 G allele, compared to the –2518 A allele, is linked with increased production of both MCP-1 transcript and protein [20, 21]. Involvement of the MCP-1 –2518 A>G promoter polymorphism in SLE development and its contribution to some clinical manifestations of SLE remains controversial [22–28]. We analysed the distribution of functional MCP-1 –2518 A>G polymorphic variants in SLE patients () and controls (). 2. Patients and Methods 2.1. Patients and Controls One hundred ninety nine (women only) patients fulfilling the American College of Rheumatology Classification criteria for SLE [29, 30] were chosen for investigation at Institute of Rheumatology in Warsaw, Poland (Table 1). Two hundred and fifty healthy women were included as controls. The protocol of the study was approved by the Local Ethical Committee of Poznań University of Medical Sciences. Written agreement was obtained from patients and controls. All participating subjects were of Polish and Caucasian origin. The mean age of SLE patients at diagnosis was 36 ± 12 years, and of controls, 35 ± 11 years. DNA was isolated from peripheral white blood cells employing a standard salting out procedure. The presence of the MCP-1 –2518 A>G (rs 1024611) polymorphic variant was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). PCR was carried out using primer pair -CTTTCCCTTGTGTGTCCCC- and -TTACTCCTTTTCTCCCCAACC-. The PCR-amplified fragments of MCP-1 that were 940 bp in length were isolated and subjected to digestion with endonuclease PvuII (CAG/CTG) (New England Biolabs, Ipswich, USA). The MCP-1 –2518 G allele was cleaved into 650 bp and 290 bp fragments; whereas the MCP-1 –2518 A allele remained uncut. DNA fragments were separated by electrophoresis on 2% agarose gel and visualized by ethidium bromide staining. Presence of the MCP-1 polymorphism was additionally confirmed by commercial sequencing analysis. 2.3. Statistical Analysis The prevalence of genotypes in patients and controls was examined for deviation from Hardy-Weinberg equilibrium. Uncorrected Chi2 test was employed to examine differences in genotypic and allelic distribution between patients and controls. Moreover, the Odds Ratio (OR) and 95% Confidence Intervals (95% CI) were calculated. A -value was considered statistically significant. Associations between clinical manifestations, production of autoantibodies, and polymorphism distribution in patients with SLE were determined by Fisher exact test. The Mann-Whitney test for nonparametric data was used to determine the statistical difference in SLE disease activity index (SLEDAI) between MCP-1 GG, AG, and AA genotype groups. Power analysis was performed using uncorrected Chi2 test, which is available at an online internet service: http://biostat.mc.vanderbilt.edu/twiki/bin/view/Main/PowerSampleSize. 3.1. Distribution of MCP-1 –2518 A>G Genotypes and Alleles in SLE Patients and Healthy Individuals Genotype analysis of the MCP-1 –2518 A>G polymorphism did not reveal a significant deviation form Hardy-Weinberg equilibrium in any group. We did not observe a significant difference in the prevalence of the MCP-1 –2518 A>G polymorphic variant in patients with SLE and healthy individuals (Table 2). OR for SLE patients with the GG genotype was 0.8629 (95% CI = 0.4428–1.682, ), and OR of the GG and AG genotypes was 0.9320 (95% CI = 0.6421–1.353, ) (Table 2). The power of this study amounted to 7.0% for the GG genotype and 6.6% for the GG and GA genotypes. We also did not observe a difference in the distribution of alleles between patients and controls. OR for the MCP-1 –2518 G allele frequency was 0.9314 (95% CI = 0.6963–1.246, ). 3.2. Association of MCP-1 –2518 A>G Genotypes with Clinical Symptoms of SLE Since the previous studies indicated the contribution of either MCP-1 –2518 GG or AG genotypes to some clinical SLE manifestations [22, 23, 28], we assessed the association of these genotypes to clinical findings in our investigated group. We observed the association between the GG versus AG and AA genotypes and AG and GG versus AA genotypes with renal manifestations of SLE OR = 3.614 (1.123–11.631, ) and OR = 2.297 (1.301–4.057, ), respectively (Table 1). However, these P-values did not remain statistically significant after Bonferroni correction (; , resp.). We observed an association between the GG versus AA genotypes with renal manifestations OR = 4.923 (1.483–16.343, ) () (Table 1). There was also an association of the MCP-1 (AG and GG versus AA) genotypes with occurrence of thrombocytopenia OR = 2.618 (1.280–5.352, ) () in SLE patients (Table 1). We did not find a significant association between the GG genotype or G allele with the presence of anti-dsDNA, anti-Smith, anti-snRNP, anti-Ro, anti-Scl-70, or antiphospholipid antibodies. There were also no significant differences in SLEDAI at diagnosis between MCP-1 GG, AG, and AA genotype groups. Completion of the human genome project revealed the existence of approximately ten million single nucleotide polymorphisms (SNPs). However, the role of SNPs in states of either health or sickness remains under investigation . To date, the MCP-1 –2518 A>G polymorphism has been associated with coronary artery disease, nonfamilial idiopathic dilated cardiomyopathy, carotid atherosclerosis in patients with type 2 diabetes, myocardial infarction, ischemic heart disease, and hypertension [33–38]. Moreover, the MCP-1 –2518 G variant may also contribute to ocular Behçet’s disease, adult and juvenile type of rheumatoid arthritis, systemic sclerosis, and psoriasis [39–43]. Reports on the contribution of the MCP-1 –2518 A>G polymorphism to SLE incidence and clinical manifestations have been inonsistent [22–28, 44, 45]. We did not observe differences in the distribution of the MCP-1 –2518 A>G polymorphic variant between patients with SLE and healthy individuals; however this may be due to the low power of our investigation. There have been no reports of a contribution of either the MCP-1 AG or GG genotype to SLE incidence in African American, Spanish, Korean, and Mexican cohorts [23–26, 44, 45]. By contrast, Tucci et al. showed a significant association of the MCP-1 AG and GG genotypes to SLE incidence in patients from North America . Moreover, Brown et al. found that Caucasians bearing the MCP-1 –2518 G allele exhibited a significantly increased risk of developing SLE . These conflicting reports on the effect of the MCP-1 –2518 A>G polymorphism to the incidence of SLE in various populations may be due to differences in the racial heterogeneity of the examined groups. This disparity may also have resulted from each population’s exposure to distinct environmental factors, which may act in synergy with the MCP-1 –2518 A>G polymorphism to change the risk of SLE incidence among the studied populations . We observed that the MCP-1 G/G and A/G genotypes contribute to renal manifestations of the disease. A correlation between the MCP-1 –2518 G allele and nephritis was also observed in a North American SLE cohort . Furthermore, the MCP-1 –2518 G allele was associated with cutaneous vasculitis in a Spanish SLE group , arthritis in Chinese adults with SLE and the presence of anti-dsDNA and antiphospholipid antibodies in Mexican patients with SLE . The MCP-1 –2518 A>G polymorphism is located at a relatively proximal position to the major transcriptional start site of the MCP-1 gene. Rovin et al. cloned the distal regulatory region of a luciferase reporter gene, including the MCP-1 –2518 A>G polymorphic variant upstream of the reporter gene . They indicated that peripheral blood mononuclear cells with either the MCP-1 AG or GG genotype demonstrated increased interleukin 1 beta-induced MCP-1 transcription compared to cells with genotype AA . Moreover, Fenoglio et al. also showed that Alzheimer’s disease patients bearing at least one MCP-1-2518 G allele exhibited a significant increase of MCP-1 levels in blood plasma . It has been reported that different renal cells, including glomerular endothelial, mesangial, and tubular epithelial cells, are able to biosynthesize MCP-1 in response to immune complexes or some proinflammatory cytokines [46–48]. This MCP-1 production by renal cells can be enhanced by the MCP-1 –2518 G variant leading to the renal manifestations of SLE observed in both our investigation and other studies . We also found that the MCP-1 GG and AG genotypes are associated with thrombocytopenia. An increase in serum levels of MCP-1 has previously been linked to elevated soluble CD40L in patients with autoimmune thrombocytopenic purpura . The platelets of SLE patients are perpetually activated, and these patients exhibit an increase of soluble CD40L levels in the blood plasma [50, 51]. The interaction of CD40L from activated platelets with CD40 on endothelial cells induces an inflammatory reaction in the endothelium leading to the secretion of chemokines, including MCP-1 . This may produce signals for the recruitment and extravasations of macrophages, which are able to interact with anti-platelet antibodies complexed with the platelets, which may lead to platelet destruction . Our genetic investigation suggests that the MCP-1 –2518 G variant can contribute to some clinical findings in patients with SLE. However, to more precisely evaluate the effect of the MCP-1 –2518 G variant on SLE manifestations, further examination of this variant’s distribution in other sample populations is required. This work was supported by A grant no. 502-01-01124182-07474, Poznań University of Medical Sciences. - I. Sekigawa, T. Naito, K. Hira, et al., “Possible mechanisms of gender bias in SLE: a new hypothesis involving a comparison of SLE with atopy,” Lupus, vol. 13, no. 4, pp. 217–222, 2004. - L. A. Love, “New environmental agents associated with lupus-like disorders,” Lupus, vol. 3, no. 6, pp. 467–471, 1994. - A. Jönsen, A. Bengtsson, O. Nived, L. Truedsson, and G. Sturfelt, “Gene-environment interactions in the aetiology of systemic lupus erythematosus,” Autoimmunity, vol. 40, no. 8, pp. 613–617, 2007. - J. C. Crispín and G. C. Tsokos, “Novel molecular targets in the treatment of systemic lupus erythematosus,” Autoimmunity Reviews, vol. 7, no. 3, pp. 256–261, 2008. - R. Januchowski, M. Wudarski, H. Chwalińska-Sadowska, and P. P. Jagodzinski, “Prevalence of ZAP-70, LAT, SLP-76, and DNA methyltransferase 1 expression in T cells of patients with systemic lupus erythematosus,” Clinical Rheumatology, vol. 27, no. 1, pp. 21–27, 2008. - W. Stohl, S. Metyas, S. M. Tan, et al., “B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observation,” Arthritis and Rheumatism, vol. 48, no. 12, pp. 3475–3486, 2003. - G. Gröndal, I. Gunnarsson, J. Rönnelid, S. Rogberg, L. Klareskog, and I. Lundberg, “Cytokine production, serum levels and disease activity in systemic lupus erythematosus,” Clinical and Experimental Rheumatology, vol. 18, no. 5, pp. 565–570, 2000. - L. Truedsson, A. A. Bengtsson, and G. Sturfelt, “Complement deficiencies and systemic lupus erythematosus,” Autoimmunity, vol. 40, no. 8, pp. 560–566, 2007. - M. Wong and B. P. Tsao, “Current topics in human SLE genetics,” Springer Seminars in Immunopathology, vol. 28, no. 2, pp. 97–107, 2006. - J. B. Harley, J. A. Kelly, and K. M. Kaufman, “Unraveling the genetics of systemic lupus erythematosus,” Springer Seminars in Immunopathology, vol. 28, no. 2, pp. 119–130, 2006. - G. Hom, R. R. Graham, B. Modrek, et al., “Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX,” New England Journal of Medicine, vol. 358, no. 9, pp. 900–909, 2008. - International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), J. B. Harley, M. E. Alarcón-Riquelme, et al., “Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci,” Nature Genetics, vol. 40, no. 2, pp. 204–210, 2008. - L. Prokunina and M. Alarcon-Riquelme, “The genetic basis of systemic lupus erythematosus -knowledge of today and thoughts for tomorrow,” Human Molecular Genetics, vol. 13, no. 1, pp. R143–R148, 2004. - I. F. Charo and M. B. Taubman, “Chemokines in the pathogenesis of vascular disease,” Circulation Research, vol. 95, no. 9, pp. 858–866, 2004. - R. A. K. Stahl, F. Thaiss, M. Disser, U. Helmchen, K. Hora, and D. Schlöndorff, “Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephriti,” Kidney International, vol. 44, no. 5, pp. 1036–1047, 1993. - B. H. Rovin, N. Doe, and L. C. Tan, “Monocyte chemoattractant protein-1 levels in patients with glomerular disease,” American Journal of Kidney Diseases, vol. 27, no. 5, pp. 640–646, 1996. - A. Saitoh, Y. Suzuki, M. Takeda, K. Kubota, K. Itoh, and Y. Tomino, “Urinary levels of monocyte chemoattractant protein (MCP)-1 and disease activity in patients with IgA nephropathy,” Journal of Clinical Laboratory Analysis, vol. 12, no. 1, pp. 1–5, 1998. - V. R. Kelley and B. H. Rovin, “Chemokines: therapeutic targets for autoimmune and inflammatory renal disease,” Springer Seminars in Immunopathology, vol. 24, no. 4, pp. 411–421, 2003. - B. H. Rovin and L. T. Phan, “Chemotactic factors and renal inflammation,” American Journal of Kidney Diseases, vol. 31, no. 6, pp. 1065–1084, 1998. - B. H. Rovin, L. Lu, and R. Saxena, “A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression,” Biochemical and Biophysical Research Communications, vol. 259, no. 2, pp. 344–348, 1999. - C. Fenoglio, D. Galimberti, C. Lovati, et al., “MCP-1 in Alzheimer's disease patients: A-2518G polymorphism and serum levels,” Neurobiology of Aging, vol. 25, no. 9, pp. 1169–1173, 2004. - M. Tucci, E. V. Barnes, E. S. Sobel, et al., “Strong association of a functional polymorphism in the monocyte chemoattractant protein 1 promoter gene with lupus nephritis,” Arthritis and Rheumatism, vol. 50, no. 6, pp. 1842–1849, 2004. - F. Aguilar, M. F. González-Escribano, J. Sánchez-Román, and A. Núñez-Roldán, “MCP-1 promoter polymorphism in Spanish patients with systemic lupus erythematosus,” Tissue Antigens, vol. 58, no. 5, pp. 335–338, 2001. - S.-Y. Hwang, M.-L. Cho, B. Park, et al., “Allelic frequency of the MCP-1 promoter −2518 polymorphism in the Korean population and in Korean patients with rheumatoid arthritis, systemic lupus erythematosus and adult-onset Still's disease,” European Journal of Immunogenetics, vol. 29, no. 5, pp. 413–416, 2002. - H. L. Kim, D.-S. Lee, S. H. Yang, et al., “The polymorphism of monocyte chemoattractant protein-1 is associated with the renal disease of SLE,” American Journal of Kidney Diseases, vol. 40, no. 6, pp. 1146–1152, 2002. - K. S. Brown, E. Nackos, S. Morthala, L. E. Jensen, A. S. Whitehead, and J. M. Von Feldt, “Monocyte chemoattractant protein-1: plasma concentrations and A(−2518)G promoter polymorphism of its gene in systemic lupus erythematosus,” Journal of Rheumatology, vol. 34, no. 4, pp. 740–746, 2007. - C. H. Liao, T. C. Yao, H. T. Chung, L. C. See, M. L. Kuo, and J. L. Huang, “Polymorphisms in the promoter region of RANTES and the regulatory region of monocyte chemoattractant protein-1 among Chinese children with systemic lupus erythematosus,” Journal of Rheumatology, vol. 31, no. 10, pp. 2062–2067, 2004. - D. Q. Ye, Y. S. Hu, X. P. Li, et al., “The correlation between monocytes chemoattractant protein-1 and the arthritis of sytemic lupus erythematosus among Chinese,” Archives of Dermatological Research, vol. 296, no. 8, pp. 366–371, 2005. - E. M. Tan, A. S. Cohen, J. F. Fries, et al., “The 1982 revised criteria for the classification of systemic lupus erythrematosus,” Arthritis and Rheumatism, vol. 25, no. 11, pp. 1271–1277, 1982. - M. C. Hochberg, “Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus,” Arthritis and Rheumatism, vol. 40, no. 9, p. 1725, 1997. - C. Bombardier, D. D. Gladman, M. B. Urowitz, D. Caron, and C. H. Chang, “Derivation of the SLEDAI: a disease activity index for lupus patients. The Committee on Prognosis Studies in SLE,” Arthritis and Rheumatism, vol. 35, no. 6, pp. 630–640, 1992. - International HapMap Consortium, K. A. Frazer, D. G. Ballinger, et al., “A second generation human haplotype map of over 3.1 million SNPs,” Nature, vol. 449, no. 7164, pp. 851–861, 2007. - C. Szalai, J. Duba, Z. Prohászka, et al., “Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 −2518 G/G genotype in CAD patients,” Atherosclerosis, vol. 158, no. 1, pp. 233–239, 2001. - A. Ogimoto, H. Okayama, T. Nagai, et al., “Association of monocyte chemoattractant protein 1 gene polymorphism with susceptibility to nonfamilial idiopathic dilated cardiomyopathy,” Journal of Cardiology, vol. 54, no. 1, pp. 66–70, 2009. - R. Jemaa, H. Rojbani, A. Kallel, et al., “Association between the −2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and myocardial infarction in Tunisian patients,” Clinica Chimica Acta, vol. 390, no. 1-2, pp. 122–125, 2008. - M. Bucova, J. Lietava, F. Mrazek, et al., “The MCP-1 −2518 (A/G) single nucleotide polymorphism is associated with ischemic heart disease and myocardial infarction in men in the Slovak population,” Bratislavské Lekárske Listy, vol. 110, no. 7, pp. 385–389, 2009. - S. Yuasa, T. Maruyama, Y. Yamamoto, et al., “MCP-1 gene A-2518G polymorphism and carotid artery atherosclerosis in patients with type 2 diabetes,” Diabetes Research and Clinical Practice, vol. 86, no. 3, pp. 193–198, 2009. - R. Jemaa, S. Ben Ali, A. Kallel, et al., “Association between the −2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and hypertension in Tunisian patients,” Clinical Biochemistry, vol. 42, no. 1-2, pp. 34–37, 2009. - S. Hou, P. Yang, L. Du, et al., “Monocyte chemoattractant protein-1 −2518 A/G single nucleotide polymorphism in Chinese Han patients with ocular Behçet's disease,” Human Immunology, vol. 71, no. 1, pp. 79–82, 2010. - A. R. Ozyürek, D. Gürses, Z. Ulger, E. Levent, A. R. Bakiler, and A. Berdeli, “Allelic frequency of the MCP-1 promoter −2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis,” Clinical Rheumatology, vol. 26, no. 4, pp. 546–550, 2007. - S. Karrer, A. K. Bosserhoff, P. Weiderer, et al., “The −2518 promotor polymorphism in the MCP-1 gene is associated with systemic sclerosis,” Journal of Investigative Dermatology, vol. 124, no. 1, pp. 92–98, 2005. - M. F. González-Escribano, B. Torres, F. Aguilar, et al., “MCP-1 promoter polymorphism in Spanish patients with rheumatoid arthritis,” Human Immunology, vol. 64, no. 7, pp. 741–744, 2003. - L. Wang, L. Yang, L. Gao, T. W. Gao, W. Li, and Y. F. Liu, “A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with psoriasis,” International Journal of Immunogenetics, vol. 35, no. 1, pp. 45–49, 2008. - E. Sánchez, J. M. Sabio, J. L. Callejas, et al., “Association study of genetic variants of pro-inflammatory chemokine and cytokine genes in systemic lupus erythematosus,” BMC Medical Genetics, vol. 7, article 48, 2006. - G. Lima, E. Soto-Vega, Y. Atisha-Fregoso, et al., “MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus,” Human Immunology, vol. 68, no. 12, pp. 980–985, 2007. - M. Baggiolini, B. Dewald, and B. Moser, “Interleukin-8 and related chemotactic cytokines—CXC and CC chemokines,” Advances in Immunology, vol. 55, pp. 97–179, 1994. - A. Sica, J. M. Wang, F. Colotta, et al., “Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor,” Journal of Immunology, vol. 144, no. 8, pp. 3034–3038, 1990. - J. A. Satriano, K. Hora, Z. Shan, E. R. Stanley, T. Mori, and D. Schlondorff, “Regulation of monocyte chemoattractant protein-1 and macrophage colony stimulating factor-1 by IFN-gamma, tumor necrosis factor-alpha, IgG aggregates, and cAMP in mouse mesangial cells,” Journal of Immunology, vol. 150, no. 5, pp. 1971–1978, 1993. - M. Nagahama, S. Nomura, S. Kanazawa, Y. Ozaki, H. Kagawa, and S. Fukuhara, “Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura,” European Journal of Haematology, vol. 69, no. 5-6, pp. 303–308, 2002. - K. N. Ekdahl, A. A. Bengtsson, J. Andersson, et al., “Thrombotic disease in systemic lupus erythematosus is associated with a maintained systemic platelet activation,” British Journal of Haematology, vol. 125, no. 1, pp. 74–78, 2004. - K. Kato, E. Santana-Sahagún, L. Z. Rassenti, et al., “The soluble CD40 ligand sCD154 in systemic lupus erythematosus,” Journal of Clinical Investigation, vol. 104, no. 7, pp. 947–955, 1999. - V. Henn, J. R. Slupsky, M. Gräfe, et al., “CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells,” Nature, vol. 391, no. 6667, pp. 591–594, 1998.

Top parenting ideas No. 6 - The family vision statement Posted July 15 Every business seems to have an attractively worded statement of vision and purpose and goals, often displayed on a plaque or on a wall. Some call it a mission statement. Employees are proud of it and hopefully do their part to bring it to pass. For many years, the late Stephen Covey was our mentor, along with his wonderful wife, Sandra. One night at dinner many years ago, Stephen asked us if we had a family mission statement, and we were embarrassed to say that we did not. I had a mission statement for my consulting company, and he said that was fine but that a family vision statement was ultimately more important — that it would draw our family together and give each child equity in the family and an identity larger than himself or herself. We began to think about how to develop one and how to get the kids involved in the thinking. About that time, we happened to meet a man who carried two mission statements — in the two inside breast pockets of his suit jacket. In the right pocket was his corporate mission statement — he was president and CEO of a highly profitable midsize company. In the left pocket (“over my heart,” he said) was his family mission statement. He told us that he and his wife had taken their three teenage and elementary-age children to a resort hotel for a long weekend, rented a conference room there and held four two-hour sessions (interspersed by swimming and activities) where they hammered out a family vision statement. He said they’d started by talking about their family, their love for each other, their desire to stay together and support each other, and how they could use what they had to help others. The dad had read them some corporate mission statements and asked if they thought one was needed in the family. At a second session, they had each written down what was most important to them and a list of their favorite words. At a third session, they’d each written up a simple personal mission statement — hopes and dreams for their individual lives. At the final session, they pulled everything together and created a family mission statement. They had a big, framed copy at their home, and each carried a laminated personal copy. We did something similar, although some of our sessions were held on camping trips and in the van on long road trips. We didn’t rush the process, and we made sure every child was involved and had a voice. We kept emphasizing the idea that this was a chance to design the type of family we wanted to have. Some of our kids were teenagers, and they decided that they also wanted to have a personal mission statement. For example, 15-year-old Noah came up with the following: “My vision is to be one who is looked upon by others and by God with a smile always. To be filled with a joy which others can feel. To find this joy through service. To watch, to absorb, to learn, to find, to discover. To always look forward to the next day.” The first draft of our collectively written family mission statement was more than a page long. Then we whittled it down to a couple of long, run-on sentences: “Create together an identity-building, support-giving family institution which fosters and facilitates a maximum of broadening and contributing by its members, each of which become strong, independent individuals, committed spouses and parents beyond their parents; first receiving and then giving the gifts of joy, responsibility and sensitivity and approaching the world with attitudes of serendipity, stewardship and synergy. “Help children to grow up and spin off into independent orbits, still feeling the gravity and light of parents with whom there is a consulting relationship in which advice is freely asked for, freely given and used or unused without offense to parent or pressure to child.” After some additional discussions, it was finally shortened to a three-word “Family Mantra” that simply said: “Broaden and Contribute.” Because it had been boiled down from longer statements and from everyone’s input, it meant something to each of us and has influenced our individual and collective decisions and directions for more than 20 years. One year, our children had it done in gold leaf and calligraphy and gave it to us on a plaque, which still hangs on our wall. Richard and Linda Eyre are New York Times No. 1 best-selling authors and founders of JoySchools.com who speak worldwide on family issues. Their new books are “The Half-Diet Diet” and “Life in Full.” See valuesparenting.com or eyrealm.com.

Thread: Deca Only Cycle? 03-08-2002, 07:14 AM #1 Deca Only Cycle? Is it even worth doing just Deca ? My friend was suggesting to do just Deca @ 400mg/week split into two injections. Would the gains be sufficiet? 10-15 pounds keepable? And since it's not the estrogen that causes problems, I believe it's the degesteron (sp?) So what can you take for it not to aromatize in that way...Nolva doesn't work right? 03-08-2002, 07:19 AM #2Member - Join Date - Feb 2002 - wonderful world of oz,where juice is free,plentiful,sterile, and not toxic to the liver i have been taking 400/ mg per week of deca and am on my 8th week and have gained 15 solid pounds,maybe just a lil water. but i have lost an inch on my waist as well,i did not have ne problems with gyno yet and this is my second cycle. the reason i stayed without as much water is b/c i took thermadrene once in the morning and once before i worked out and wallked for 20 minutes/ day,have seen pretty impresive results, stats are 6'2 275 16% b/f give er take a percent 03-08-2002, 07:59 AM #3 I have heard of folks doing just deca by itself and gotten good gains. I personally would not. Deca takes a while to get into your system hince ST8's 8th week gains, and he will probally keep his gains for a while because even after you stop deca it takes a while to get out of your system. Personally I would stack it with something fast acting like dbol , until the deca "has a chance to kick in". But sure why not Ter, since you have all the money to blow.. send me some while you are at it, deca I mean not money. Well okay you can send me some money too if you would like. 03-08-2002, 08:14 AM #4Senior Member - Join Date - Jan 2002 03-08-2002, 08:20 AM #5 honestly this question has be asked so many times... ten you know this answer. most of the guys here will tell you not to do a deca only cycle because of deca dick and the fact that when its mixed with test you have an excellent mass/strength gaining cycle. you have done tons of research and im sure you have found that TONS of people do this and get results. BUT if you want major results and want to be SMART.... add test and/or dbol and you are set. HOWEVER, do dont ANYTHING unless you are preapared for the: dedication, have been training for a while, know what it is to have a diet (whether that means to lose or GAIN weight), the consequences (if any), etc 03-08-2002, 12:34 PM #6 no AS should be done alone. always stack to take advantage of the true potential of each steroid and their combination, synergy. 800mg/wk of deca can cause some major progesterone levels in the body. the only thing that will get rid of this is a birth control, and also abortion pill, called ru-486. this is very expensive and i heard physicians make the girl take the pill in the office in front of them for some reason. it's not worth it. just stack the deca with some dbol and test and you'll be set. 03-08-2002, 12:44 PM #7 03-08-2002, 05:52 PM #8Junior Member - Join Date - Jan 2002 I have been using Chrysin/Dim (Diindole methane) gel from Rx3k.com to combat estrogen/progesterone buildup. I believe it works. I have been using HCG , Test and DECA during my cycle and believe I was getting a little DECA dick (I was getting lots of aromatese). After using the gel, I am horny like in the beginning of the cycle. The only problem with the pharmacy is that its in Canada and the guy says he cant send it to the US these days because of security. Medlean (medlean.com) also makes an anti-estrogen that is supposed to combat progesterone from DECA. 03-08-2002, 08:14 PM #9 k thnx guys, helps Users Browsing this Thread There are currently 1 users browsing this thread. (0 members and 1 guests)

The Division of Nursing is proud to recognize the nurses and collaborators at Dayton Children's through several award and recognition programs. In collaboration with Wright State University, every year we recognize one of our nurses as the Cameo of Caring. This is a very prestigious award that only ten Dayton Children's nurses have received since the programs inception in 2001. The Excellence in Nursing Award recipients are recognized every year for their outstanding nursing practice based on our Professional Model of Patient Care, Synergy. Dayton Children’s also offers the DAISY Award as another way to recognize the valuable contributions of its nursing staff. All nurses, in any role, may be nominated and considered for a DAISY Award. The opportunity for all nurses in the hospital to be recognized sets this apart from nursing recognitions now offered. In addition to recognizing nurses, the Division of Nursing also recognizes non-nurses for their contribution to the education and professional practice of nurses, collaboration with members of the care team, and creating a positive work environment. These recipients are recognized as Collaborators of Caring. Dayton Children's received Magnet designation®. on November 22, 2013. Magnet designation is nursing’s highest honor, meaning Dayton Children’s Hospital has been recognized nationally as the gold standard in patient care and the professional practice of nursing by the American Nurses Credentialing Center (ANCC). Dayton Children’s is one of only 31 pediatric Magnet hospitals nationwide and one of 26 Magnet hospitals in Ohio. The 393 Magnet designated organizations represent less than 7 percent of all U.S. health care organizations. Magnet hospitals have lower patient mortality, fewer medical complications, improved patient and employee safety, and higher patient and staff satisfaction.

Return to Transcripts main page THE NEXT LIST BjarKE Ingels' BIG View of Architecture Aired January 22, 2012 - 14:00 ET THIS IS A RUSH TRANSCRIPT. THIS COPY MAY NOT BE IN ITS FINAL FORM AND MAY BE UPDATED. BJARKE INGELS, ARCHITECT: If we could do anything, what would we really do? What are the things that we lack in our city? Whyat are the things that we would like to do, but we can't -- and then make them happen. That's exactly what architecture should be all about. DR. SANJAY GUPTA, CNN: That's just a small window into the mind of the man we are about to meet. He's a young Danish architect named Bjarke Ingels. His bold, innovative ideas are puching the boundaries of design around the globe, including the Manhattan skyline. But he's not just dreaming up pie-in-the-sky projects, he's actually getting them built. You see, to Ingels, architecture is not aobut building monuments, but about creating possiblities for human life. I'm Dr. Sanjay Gupta. Welcome to THE NEXT LIST. INGELS: In the big picture, architecture is the art and science of making sure that our cities and buildings fit with the way we want to live our lives. The West 57 project is a really beautiful site. It's overlooking the Hudson River, has a view like we have here. It's perfectly oriented towards the south and the west. But it's, you know, right where the West Side Highway takes off, and it's in Hell's Kitchen -- as you can imagine from the name, it's like a -- it's a pretty sort of industrial neighborhood. So we thought that maybe it could be interesting to really create a sense of place. Having spent 10 years of our career in Copenhagen, trying to escape the tyranny of the typology of the courtyard building (ph), it could actually be an interesting thing to rediscover in Manhattan, if you like, the - European courtyard is that the architectural scale what Central Park is at the urban scale, like an urban oasis at the heart of that city. This is the West 57th Street project. As you can see, it's this mixture between a skyscraper and a - and a courtyard building, and it just sort of open up the courtyard for the views. It sort of tilts from being horizontal to being almost vertical, opening up the entire courtyard for the sun from the south and the west, so you would be able to see the sun set over the Hudson River. And the bottom, like the southwest corner, is 42 inches, so it's really the height of a handrail. And here you're up like 430 feet, so you have this sort of incredible sort of from the - from the human scale to the - to the city scale in one single building. ROBERT A.M. STERN, DEAN, YALE SCHOOL OF ARCHITECTURE: It's a big idea that caught everybody's attention. It's just the kind of idea that when you see it, you say how come nobody's thought of it before? DOUGLAS DURST, DEVELOPER, WEST 57th PROJECT: I describe him as a genius. He doesn't fit the - what you think of as an architect. He's fresh, he's - he's very young, but he is, I think, a true genius in the sense of being able to see designs in his mind and put them down on paper better than anybody I've met. INGELS: Today a lot of people have this feeling that, you know, they ask why are all modern buildings so boring? And essentially, you say, like modern buildings have degenerated into these big boring boxes where the architecture is very passive and all the quality that makes the space inhabitable is this like onslaught of machinery that pumps air and light into the building. So what we're interested in is what you could call engineering without engines, that essentially we use contemporary technology, our capacity to simulate and calculate the performance of a building, to put the attribute into the actual design of the building, the way it's structured, the way the windows are proportioned, the way it's oriented to try to capture the sun or create shape. So, in a way, find new ways of - in forming the architecture, the design of the buildings. So, essentially, what we're interested in is buildings that look different, because they perform differently. STERN: Bjarke has had a capacity to read deeply into the situation, the zoning, the economics of a project, the constructability of a project in the way that most architects tend to say, oh, the zoning is constraining. He sees the zoning - I won't say is liberating, but as something if you master it, you can move on to a higher level. INGELS: I think all projects always start with some kind of anxiety that this time we simply never are going to get there. Like you have this feeling maybe it's simply not going to come out, like no matter how hard you squeeze, it's simply not - it's not getting there. So, for each project, we might have like even like hundreds of models that are each like early attempts to capture an idea in a - in its most blatant form. So no idea is allowed to exist only inside the head of one of the collaborators. It has to come out in a diagram, in a drawing, in a physical model. You might walk around with a brilliant idea inside your head because you - if you don't bring it out there, I'll never be able to respond to it. Nobody will be inspired and nobody will be able to inspire. INGELS: In St. Petersburg we're doing a competition for a public pier. You know, St. Petersburg is a - is a wonderful city. You have wonderful parks, you have birds sitting in the trees, you have manatees in the water, you have pelicans. So it's like it's this little paradise on earth. So there's not a big problem to solve, but still there's this almost like rooted in the DNA of the city, is this idea that the pier is where the whole city comes together to meet. So, in this case, rather than solving a problem we had to sort of try to create a potential for something new. Instead of dumping some arbitrary building at the end of the pier, we thought what if the pier itself could simply come out of the water and become its own pavilion, the pavilion where all the citizens can gather? And, of course, in some way it also creates this sort of a magical draw. We imagine the flow of people come together in what we call the wave walk. A whole series of activities that brings daily life in more direct contact with the water. UNIDENTIFIED FEMALE: I like it a lot. I like the lights and how it reflects on the water, and the circular movement of the whole thing. It's really pretty. UNIDENTIFIED MALE: It's iconic. You look at it, it's distinctive from anything else that you'll see in Florida, let alone the Eastern seacoast of the United States. And I think it will put St. Petersburg, architecturally speaking, on the map. UNIDENTIFIED MALE: It's an amazing architecture. If you can have that much structure with all the glass and everything in it, to me it's amazing that they can do that. INGELS: The project we proposed is pretty - is pretty wild. The inverted pyramid that we're replacing is also pretty wild. You - well, you do ask yourself if this is too crazy, and then - but then, when you go through all of the questions and answers, you see what kind of parameters are we responding to. Although unexpected and maybe unusual, it actually feels like the right thing to do, and I think this is one of these unique situations where something insane as the - as the whole world looping upside and down or inside and out, actually seems like it could be the right answer to this specific situation. You can say like Planet Earth has an existing geology, and what we do as - as human being - human beings and as architects is that we try to sort of alter and modify and expand the geology. And, when you look at it this way, you realize that our cities and our buildings and architecture isn't the way it is because there's some kind of universal law that says that's how it has to be. They're the way they are because that's how far we got the last time we tried. And since it's an ongoing experiment, like human presence on Planet Earth is constantly evolving and so should architecture in our cities. Architects have to become more than just designers of two-dimensional facades or three-dimensional architectural objects. We have to become designers of ecosystems, systems of both ecology and economy. The channel, not only the flow of people throughout things and buildings, but also the flow of resources, like heat, energy, waste and water. Stop seeing our presence, like the human presence on Planet Earth, as sort of detrimental to our ecosystem, but actually try to sort of integrate and incorporate our consumption patterns and our leftovers into our natural environment. Sustainability can't be like some kind of a moral sacrifice or a political dilemma or even like a philanthropical cause. It has to be a design challenge. This is the Danish Pavilion in Shanghai. The Danish Pavilion was part of the - of the Shanghai World Expo that dealt with sustainable cities, and our idea was to try to capture all of the elements of Danish city life, where the fact that the city is sustainable increases its life quality. Thirty-seven percent of Copenhageners commute by bicycle, means that they're never stuck in traffic, they never have to sit and try and - in a traffic jam. They can move freely to and from work. And, at the heart of it, the harbor bath, sort of a sample of clean water where people can actually paddle and - and swim, with the Little Mermaid, the national symbol of Denmark that we actually managed to kidnap for six months. We decided to place the Little Mermaid of Denmark, not a copy of the mermaid. We actually moved her to China. We had to wrest her out of the hands of the Danish equivalent of the Tea Party, who was trying to pass a law specifically against moving the mermaid. We had to get her through Chinese customs, and there she is. INGELS: I grew up in north of Copenhagen. My parents live in the house where I grew up. So they have like a tiny little house on a beautiful sloping side down to a lake and a forest. And every - every fall, there's some storms and normally like one tree from the forest like comes down. In this case it came down over the - the sort of wooden fence into the forest. So suddenly we had a lot of lumber, and the idea came that we could build a fort for - I was a kid at the time. So, since I was already drawing a lot back then, I got the idea that I would - I would draw this fancy fort, sort of a hybrid between some Western thing and some - like the Roman forts. And of course I designed some kind of massive castle, with like four towers and like a drawbridge that came down. There was a moat around it. So it was pretty - pretty full on enterprise. And then my first experience with (INAUDIBLE) engineering, my dad pretty much boiled it down to an (INAUDIBLE) box. But still, you know, I felt that I had been significantly involved in the design process and the construction process, although it was a much more optimized version than my original fantasy. I mean, I think it was my first experience with how it is, and I was - unless you really begin with the - with the parameters of reality, you'll end up sort of amputating your ambitions quite quickly. I have two siblings, a big sister and then a much younger brother. So I think the first half of my childhood, I was definitely my big sister's little brother. And then I definitely became my little brother's big brother, which - which I think is almost the ultimate education in life you can get is to assume both roles. I think among the three siblings, we sort of divided the talent between us. So my sister was singing and playing the piano. I had piano lessons for five years and I have practically no keyboard skills left to show for it. My little brother is the sort of a numbers genius, and I was always good at drawing. Throughout my life I've always been in a way the best guy in the room at drawing. UNIDENTIFIED MALE: Great work. I always loved your work. INGELS: I had imagined that I would have become a cartoonist or a graphic novelist. Then of course I got fascinated by architecture and lost trace of my original scheme. I had a very interesting professor, this sort of neo-hippie, definitely a flower child when he was a kid, and he was like - and his person and his approach has been an inspiration. When I was in school, on the first day of the - of the year, he gave this opening speech, and he basically said that he didn't care if we learned this or that or like follow the curriculum or whatever. All he wanted us to promise him, and this we had to promise, was that when we were - when we graduated, we would leave the school with something at heart. He meant that we shouldn't just go out there and, you know, show the world what we can do. We should go out there with the intention of contributing somehow to life, to society, that it had to do about caring for how people are going to inhabit the spaces and live in the cities and move around. Just not looking at architecture as some kind of stylistic exercise or some kind of aesthetic practice, but really being about creating possibilities for human life. GUPTA: Creating possibilities. It's the goal of every project Bjarke Ingels takes on, and coming up, he shares his passion for big ideas. INGELS: I came here to Yale to teach studio, which is sort of a class where a group of students, 12 students, are given a real challenge. So essentially what we would like to do for this - for this studio is to look at the idea of social infrastructure. The specific idea is to make an inhabited bridge, to propose a bridge over the East River of New York, where what carries the bridge is not going to be just steel and concrete, but it's actually going to be inhabited structures for apartments, spaces for living and working, maybe a little piece of park, a bicycle path. We're just going through the harbor to see what would bridges be like as buildings. So basically when you see them from the water, looking up at them, what would a bridge be like a building. So like when you see these bridges from below, you always feel like it would be amazing if you could crawl around in these girders and like go where you're not supposed to go. The idea of the studio is to see what if you could actually go, what if people were really living inside the bridge. JAMES SOBCZAK, YALE STUDENT: A huge scale. I mean, you look at some of these bridges, compare it to actual buildings and skyscrapers, then they're actually quite bigger than them and a larger span. KARL SCHMECK, YALE STUDENT: Bjarke I think is doing things in architecture right now that nobody else is doing. He's doing the kind of projects the way they're explained, the partnerships that he's creating and also their idea of synergy, bringing together a lot of different disciplines. I think this is something really novel, and Bjarke is doing it better than anybody else right now. INGELS: What we tried to do is to make a project where the potential for private profit can actually create some amazing public opportunities. But also the value that it generates to certainly have a lot of real estate in the middle of the water, with amazing views looking up and down the river, probably the best views in New York, that value can actually contribute to paying for the bridge. STERN: It's a big idea that got lost in the shuffle of big ideas, and bringing it back in a new way, it'd be - it should be astounding, what he does. INGELS: The big goal of the - of the studio is this sort of pragmatic Utopian approach, to give the students the tools and the skills to approach the sort of almost the unimaginable or like the wildly creative with a very practical and straightforward approach. The more wild ideas you want to realize, the more drive and rational and professional and rigorous you have to be in your approach. Because if you're just going to do the standard solution, you can actually be quite lazy, because nobody's going to question anything, so you can just do it. Whereas if you want to go just even a little bit beyond sort of the conventional path, you really have to try hard to convince a whole - a whole series of authorities and also clients and investors and neighbors that this is actually feasible. SOBCZAK: I think it's kind of fun, especially in school, to make these kind of more Utopian, kind of out there projects and really kind of push the boundaries of what may be possible or what could be. DURST: He's annoyingly young and annoyingly brilliant. When you first meet him you would want to dislike him for those reasons. But he's a charming person and so open that you just can't help but like him. INGELS: And also in Copenhagen, this building called the 8House, which is almost like a hybrid between a mountain village and a Copenhagen courtyard building. People can actually walk and bicycle all the way to the penthouse in the middle of the city. So here, this is the view from the - from the top path, where you look out over the flat landscape of Copenhagen. It's a big park. You know, the lake here delineates the city limits, so you really have cows grazing on the other side of the water, a sort of meeting between man and cow. And essentially what it does is that it sort of amplifies the topography of Copenhagen, this like completely flat landscape suddenly gets a place where you can go for a walk hand in hand with your girlfriend, and check out the amazing view that you wouldn't have otherwise. So, in a way, the building also becomes part of the - of this manmade landscape itself. As architects, we try to sort of observe life, see what are people doing, and then we try to see what is it that people want? What is it that they desire? Why do they - why do did they move into the suburbs in the '60s and '70s to get a private garden? Why are they moving back into the cities now? why can't you have both? That's exactly what architecture should be all about, is to try to make the world a little bit more like our dreams. Essentially ask ourselves, what would be - if we could do anything, what would we really do? Like what are the things that we lack in our city? What are the things that we would like to do, but we can't, and then make them happen. GUPTA: There's no question Bjarke Ingels sees the world a little differently, and it's easy to see the passion he brings to his work. He is challenging us to rethink what architecture can do for everyday people and re-imagine the world as it could be, and that makes him an agent of change and earns him a spot on THE NEXT LIST. And for more on THE NEXT LIST, you can go to CNN.com/TheNextList. You can also go to my life stream at CNN.com/Sanjay. I'm Dr. Sanjay Gupta. Thanks for watching. See you back next Sunday.

Bill Peterson Rumors The Orlando Magic have named Bill Peterson as head coach of its D-League team, the Erie BayHawks, Magic General Manager Rob Hennigan announced today. Per team policy, terms of the deal are not disclosed. “We are excited to welcome Bill (Peterson) and his family,” said Hennigan. “Bill’s passion for teaching and development fit seamlessly into our vision of creating a culture of collaboration and synergy between the Orlando Magic and Erie Bayhawks. His wealth of knowledge and experience will help our players fulfill their ultimate basketball potential.” Milwaukee Bucks assistant coaches Joe Wolf, Sidney Moncrief, Chris Gilmartin, Bill Peterson and Anthony Goldwire will not have their contracts renewed, club officials confirmed Wednesday. New Bucks coach Larry Drew is in the process of putting together his own staff. Although nothing has been announced yet, two of his former assistants in Atlanta, Bob Bender and Nick Van Exel, helped Drew run the team’s draft workout Wednesday. There is a sizeable faction of the team’s basketball operations that is baffled and, if not upset, miffed. Unlike Hammond, Skiles and Weltman, who all received contract extensions last summer, there are more than a dozen Bucks employees who’ll see their contracts expire within the next couple of months. That includes all the assistant coaches: Jim Boylan, Kelvin Sampson, Joe Wolf, Bill Peterson, Anthony Goldwire and Jason Staudt.

If might not seem like it at the moment, but this fall, you can probably bet on “The Imitation Game” getting a massive push from The Weinstein Company. Why? Well, when they picked up the movie earlier this year, they paid a staggering $7 million dollars for it. Clearly, they think the Benedict Cumberbatch and Keira Knightley starring drama can and will go very far this awards season, and perhaps that means making sure every single element is up to their exacting standards. Film Music Reporter reveals that though Clint Mansell was first signed on to score the picture, he’s now been replaced by the very busy Alexandre Desplat, who this year alone has dropped scores for “The Monuments Men,” “The Grand Budapest Hotel” and “Godzilla” and still has Angelina Jolie‘s “Unbroken” on deck. So why the switchout? No word yet, Mansell doesn’t seem overly busy at the moment, but perhaps director Morten Tyldum is looking for a different vibe for his picture. Either way, both Mansell and Desplat are some of the best in the game, and while losing one is a bummer, gaining the other ain’t so bad. Meanwhile, Variety reports that pop star Patrick Wolf will score the developing Noel Coward biopic starring Chris Colfer. “I am so thrilled for my first film soundtrack composition to be about Noel Coward’s early life. We both grew up in the same parts of South West London, and began our journeys onto the stage and into writing at the same precocious age,” Wolf said. “The script, director, Noel Coward Estate and the cast attached combined are already in perfect synergy to make this something magical.” Production on the movie begins later this summer.

Katusha on fire Muscat turned on some near perfect sailing conditions for the start of fleet racing at the RC44 Oman Cup presented by Oman Shipping Company. The sea breeze clocked in at noon and continued to build from 9 to 15 knots throughout the afternoon bringing with it a big rolling swell. The conditions however couldn’t separate the fleet of thirteen RC44s who seemed to arrive at the windward mark in unison, causing difficult mark rounding’s that kept the umpires busy. Katusha (RUS) was on fire and dominated the day, winning the first two races and making a great recovery in the last to finish third, even after picking the un-favoured left side up the first beat and being buried at the top mark. Steve Howe, standing in for owner Gennadi Timchenko at the helm of Katusha this week, put their day into perspective: “Yesterday was a good day and we tried to keep the same plan for the fleet racing today, get a good clean start, sail the shifts and get around the race course ahead of the fleet. It’s one design sailing at its best, you have your good days, your bad days and it’s going to happen when you have a bad race like we almost had in race three, but you just have to focus and minimise the risk.” Chris Bake’s Team Aqua (GBR) was hot on Katusha’s tail, finishing second in both the opening two races and sixth in the third. But a collision in the final race resulted in a dramatic end, seeing the American team’s scoop rip away from the hull. A protest was lodged by Ironbound’s new tactician Paul Goodison and after much debate in the protest room, Team Aqua was disqualified from race three and given three additional penalty points, dropping them from second to sixth overall. Ironbound was awarded redress leaving them third in the overnight standings. Artemis Racing won the final race of the day after what had been an indifferent start for Swedish team. They had picked up a penalty in the first race for missing the offset mark and again in the second for trying to squeeze inside MAG Racing at the leeward gate. Owner Torbjorn Tornqvist who arrived in Oman this morning was pleased to end the day on a high note. “The third race finally went really well. We hope that the good results will stay for the rest of the regatta but you never know. There are so many good boats here, from year to year all the teams are getting better, the new teams learn from the established teams and they obviously improve which is good to see. Some you win and some you lose but we are happy with the way we are sailing at the moment, we have good boat speed, good handling, no issues.” Sitting in second place overall after Aqua’s disqualification is Brian Benjamin’s Aegir Racing. The team from England came 13th in Croatia last October and are clearly enjoying the valuable input this week of their guest tactician, Russell Coutts. In a further incident between Team Italia and RUS 7, the Russian team were given three penalty points for damage. Racing at the RC44 Oman Cup presented by Oman Shipping Company continues through to Sunday 3rd February with the first warning signal on Friday at 12.30 (GST). Results - RC44 Oman Cup 2013 presented by Oman Shipping Company 1 Katusha – 1 1 3 – 5 2 Aegir Racing – 6 3 7 – 16 3 Ironbound – 4 6 7RDG – 17 4 Team Italia – 8 5 6 – 19 5 RC44 Team CEEREF – 7 11 2 – 20 6 Team Aqua – 2 2 14DSQ (3) – 21 7 Team Nika – 5 8 8 – 21 8 RUS7 Sail Racing – 3 7 10 (3) – 23 9 Artemis Racing – 12 10 1 – 23 10 Lunajets Aleph Racing Team – 10 4 9 – 23 11 MAG Racing – 11 9 5 – 25 12 Synergy Russian Sailing Team – 13 12 4 – 29 13 Peninsula Petroleum Sailing Team – 9 13 11 – 33

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Wax Tailor Interview Author: Adam Bernard French hip-hop/trip-hop/downtempo producer Wax Tailor has been on a steady ascent since his days releasing work as a part of the group La Formule. He started using the Wax Tailor moniker in 2001 and last month he released his third full length album, In The Mood For Life. This week RapReviews caught up with Wax Tailor to find out more about the project, how his everyday life at the time of its writing and recording played a major role in it, why he uses guest appearances sparingly, and what excites him musically in 2009. Adam Bernard: Let's start by talking about your latest album, In The Mood For Life. When you sat down to make it where were you mentally and emotionally? What were you looking to put into these tracks? Wax Tailor: It was the moment when I had just handed in the second album, Hope & Sorrow. In my mind I was already thinking about this new album. What I had in mind was about the code arrangements because I think it was the point I was really upset about. I think I wasn't ready, or really professional, about the recording for these kinds of things and I really wanted to mix some sampling elements and some code arrangements. I'd been working a lot on this; searching, hearing, listening to a lot of albums, trying to understand how I could make it. I'd been searching for the right tools, for the right sound engineers, the right studio, the right musicians, and finally the writing. It was a bit different for me because when you go this way it's very different and I think in the end this album is a bit different because it's more harmonic and at the same time it's orchestral. AB: When you listen to the record what do you, personally, get out of it? WT: What is funny is that a lot of people who have talked with me about this album have said it's more positive. That's not exactly how I feel. I feel more like there is a kind of energy and the synergy for me is more about the feeling I had while I was doing it and it was more about, I wouldn't say hunger, but a kind of struggle I felt every day. I really had this in mind and when I listen to this album I think, maybe because I know it from behind, about the energy I had and the feeling I had, because the cycle of In The Mood For Life is not a very happy thing, it's more being able to struggle every morning about life. AB: It's interesting the way you just described it because the cover image has a man underneath an umbrella in perfect weather with the exception of right around the umbrella, where it's pouring. WT: I was searching for a kind of symbol of this. You have a character, he's walking, it's very shiny and sunny everywhere, but it's raining under his umbrella. It's like a very bad, unlucky, guy, and at the same time he's just watching it fall, he's not like "I'm unlucky, I'm unlucky," it's more like "OK, that won't stop me." That's exactly what I had in mind. AB: For this album you once again work with Charlotte Savary, whom I absolutely love. She actually reminds me a little bit of Emilie Simon. How did you originally link up with her and why do you feel you two work so well together? WT: She was preparing an album six or seven years ago with a band and a friend of mine was producing it, so I just met her like that. I came a few times to the studio and she was really cool, I had a good feeling with her. That was the same moment I was preparing my first EP, so I had the idea of trying a different version of a track with her. It was really cool and after that I just proposed to invite her on the first album. I realized that we were very linked about special moods, like melancholy songs, and each time I get a kind of melancholy track I don't even think about who I could work with, I just think of her. AB: Do you gel with artists easily, or do you find it hard to find people to work with? WT: It's not too difficult, but I try to be careful about the featuring. You know, as a lot of people, about name dropping and things like that and because of what happened on the second album it was quite easy to have some supposed big name. The people I work with in the record industry, they tried to do it this way, like "maybe you could connect with this guy or these guys," just because it's going to help in selling an album. From my point of view, though, it's not true, because I think the people feel when it's true or not. Sometimes, for sure, you can have some fake featuring and that works, but most of the time the people don't share anything, they don't have any conviction about what they do, so I try to be really careful about that. That's the only thing, except that's not so complicated because I try to work with people with a specific idea. I never send five or six tracks to an artist saying just choose one track, I just send a track saying I got a specific idea that fits this song and I want you to sing, here's the mood, etc., and in the end it's just a yes or no, that's all. AB: I can't stand when you look at the back of an album and can tell there are a slew of guest appearances that were done solely to sell the album in certain markets. I was actually just having a discussion with some friends of mine about this. I was telling them about some emcees that are really dope but they didn't want to hear it, they wanted someone "major." WT: Yeah, the problem is a lot of people in the industry think like that. They don't realize the people that buy a Kanye West album don't care about a Kanye West feature on just one track. There is nothing to share on this kind of thing. I think it's really important to think sensibly. AB: A lot of "producers" have popped up over the past few years thanks to computer programs that make it easy to be mediocre. What are your thoughts on the scene becoming so crowded? Does it make it more difficult for the great artists to be heard, or do they stand so far head and shoulders above the pack they become even more obvious than before? WT: I think it depends. We have more and more tools and at the same time there are more and more people and I think we both know a lot of people say they are producers and in the end it doesn't mean a lot. It's not so easy for the reasons you talk about, but at the same time I think, I don't know how to translate it exactly, but it's also a way to be sure about the people who really want to go on. I know a lot of people who say "it's too complicated" and I just think it's impossible for me to do something else. AB: What's getting you excited musically at the end of 2009? WT: I like the idea of past and future at the same time. In '94 I bought some equipment, like an Ensoniq Sampler. Fifteen years after I'm still using this stuff, but I definitely don't work the way I was doing it fifteen years ago because I also have some tools from 2009 and I like the idea of mixing those elements. I think it's the same for a lot of things. Sometimes I think we're in a very bad period about the music industry, but at the same time we have crazy tunes we've never had, so you have two ways to think of it; being very negative and thinking about the bad aspects, or just trying to convene and thinking let's use the best of both worlds and do the best we can. The latter is the way I try to work right now. AB: Do you feel you're living the dream, or do you have another goal, perhaps not even music related, that you have left to accomplish? WT: Well, there are a lot of things left to accomplish, one I've had in mind for a long time is making an original soundtrack. I made an original soundtrack for a documentary movie four years ago and I got a lot of proposals from that, but the problem is more about the schedule because half the time I'm in the studio for my album and the rest I'm on the road. I'm also a manager and producer, so I've got a lot of work, but I think after this tour, maybe if I have a good offer on a project I'm excited about, that will be my next goal. You can check out Wax Tailor on the web at WaxTailor.com. Hope & Sorrow is in stores now! Originally posted: October 13, 2009

What would possess almost 20 million grown-ups to visit Disney World each year without a kid in tow? Lauren Lipton travels to the Magic Kingdom in search of the spell There are 5 Disney resorts and 11 Disney theme parks on the planet, and until recently I had no interest in visiting any of them ever again. I was raised in California and loved Disneyland, the West Coast outpost, when I was of Disneyland-going age. Then I grew up. My taste matured, as one’s taste is supposed to. In the last 20 years I have entered Disneyland only once, out of parental duty, and had never set foot in Walt Disney World. But I may be the exception. About a third of the 51 million annual visitors to Walt Disney World, which includes the company’s crown jewel, Disney’s Magic Kingdom, are adults without tykes in tow. I even know a few. It turns out that plenty of my cosmopolitan friends can’t get enough of the The Most Magical Place on Earth—a fetish I’ve discovered only recently, now that everyone posts their vacation plans on Facebook. “Oh, my gosh, I love Disney!” gushes Marie Bostwick, a best-selling novelist who once up and moved to Mexico City for the adventure of it. I was flabbergasted to learn that she and her husband, a corporate chairman (they now live in Connecticut), have visited Disney dozens of times—with their kids and without. “You just have to embrace the cheesiness,” Marie says, before she starts going on about fireworks displays, rides, live entertainment, and lazing by the pool with a book. And it isn’t just that the place offers something for everyone, she tells me: At Disney, one is allowed to embrace one’s inner child, the happy innocent who is full of wonder and not afraid to look like a dork. It’s an escape, a kind of regression therapy set to the tune of “It’s a Small World.” Still…is it worth the trade-off? There is an entire planet’s worth of art, architecture, and culture to discover, and time off is precious. Why would any adult choose to squander it in a place associated with screeching toddlers, brutal lines, mediocre food, and a preponderance of twee? I can understand that there’s a lot to do and even that some people want to be kids again. But I like being an adult. And I can never quite let go: I obsessively look for cracks in the facade, and get cagey at the idea of letting corporate America manipulate my emotions. However, I am an open-minded person and can see that there might be some value in cultivating a more carefree, innocent self. So I’ve decided to spend six days and five nights within the 40-square-mile confines of the Walt Disney World Resort. I’ve asked Marie to be my Tinker Bell for the first few days, sprinkling me with pixie dust and encouraging happy thoughts. Then she’ll return home, and my husband, a world-weary journalist and world-class skeptic, will join me. As for our 13-year-old son, it’s midterms week at school. I’ve reluctantly left him behind. Just off the plane from New York, on the curb at Orlando International Airport, I board Disney’s Magical Express bus service for the place where dreams come true. Okay, Disney, I think, as the wheels start turning and an orientation video begins to play, work your magic. I am pretty sure this won’t be easy. The price of a ticket to the Magic Kingdom on opening day, in 1971. The price of a ticket to the Magic Kingdom Disney’s Yacht Club Resort, the first of four hotels where I’ll stay, is part of a 1,200-room complex of cupola-topped gray-and-white buildings sited on a 25-acre Disney-made lake. The place evokes nineteenth-century Martha’s Vineyard, except with palm trees and powerboats. New York this morning was leaden and cold, but the Yacht Club is all cerulean sky and emerald lawn and beds of flowers wafting a sweet, subtle perfume. At the edge of the ersatz bay is a decorative lighthouse; in the distance, an old-fashioned boardwalk hugs a curve of shore. Three handsome sailors stride past, looking as if they’re on leave for Fleet Week. To enter Disney World is to enter a world of illusion made possible by the company’s unparalleled attention to detail. Every area at Disney has a “history,” from the iconic Cinderella Castle to Typhoon Lagoon, a surf pool supposedly created by a make-believe storm, and Big Thunder Mountain, the fictional former center of an 1850s gold-mining operation. Guests board this roller coaster, the company says, “at the ramshackle headquarters of the Big Thunder Mining Co., in the town of Tumbleweed, established during the Gold Rush.” The company also makes shrewd use of background music; a merry sound track plays just at the threshold of your consciousness nearly everywhere you go. Fragrance is another special effect: During Soarin’, a ride that uses a filmed background to simulate a hang-glider flight over California, the scent of citrus blossoms circulates as you fake-swoop over an orange grove. According to lore, Disney even lends a homey feel to the Main Street U.S.A. area of the Magic Kingdom by pumping out the aroma of freshly baked cookies. Keeping this massive illusion alive also requires the commitment of tens of thousands of workers, who at Disney are called “cast members.” The sailors I see are in fact costumed employees, as is the blue-blazered “captain” who appears in the Yacht Club’s brass-accented lobby from time to time to welcome guests. Their commitment to their roles is flawless and impressive. From time to time I must remind myself that the princesses, pirates, and historical figures running around are just actors who clock in and out every day, and that everything here was manifested out of a swamp by Walt Disney in the late 1960s. In fact, one’s reaction to all of these little fakeries depends on how open one’s Disney chakra is. As a child, I had no problem accepting Disney’s make-believe world. Now I think all of this pretense borders on the bizarre. As the vacation wears on, I will become increasingly distracted trying to separate the genuine from the counterfeit. Marie will chide me again and again to “relax, have a good time, don’t overthink it.” But already, 15 minutes in, I’m a little unhinged: While I wait in the Yacht Club’s gardens for Marie to arrive from the airport, I puzzle over whether the petunia scent could be simulated, whether the chirping birds I hear are a recording, and even whether the egrets wandering around the lawns are animatronic. If you don’t know what’s real and what isn’t, how can your reaction be honest? Is happiness real if it is a response to an idealized facsimile of a pleasurable thing? I need a drink. The bar at Stormalong Bay (a.k.a. the pool area) is pleasant and civilized, populated by attractive people in business attire who sit at tables and work on their laptops; they’re either here for a corporate convention or they’re cast members portraying people here for a corporate convention. The area is almost child-free. A few giggling tots splash around, but most, it seems, are still out at the parks. Missing my own kid, who would no doubt help get me into the spirit of things, I text him to say “Wish you were here,” and order an $8.75 rum cocktail called a Banana Cabana. Like everything at Disney, it’s sweet and goes down easy. The number of square miles of Disney World The percentage of property designated a By the time Walt Disney World opened in 1971, its creator was not around to see it. Walt Disney’s first theme park, Disneyland, in Anaheim, California, had been a success since 1955, but Walt had a bigger vision: an entertainment megalopolis supported by a workforce that would live nearby in a utopian city of his own design. Born and raised in the Midwest, Disney was the quintessential American—optimistic, self-made, patriotic. He romanticized the future and the past over the complicated, sometimes disagreeable present. It is said that he built Disney World in part because he was dismayed by the tacky motels and fast-food joints that had sprung up around Disneyland. (A time-honored American solution to a spoiled landscape: Move to an unspoiled landscape and start over.) Disney died of lung cancer in 1966, less than six months before construction began on his American heaven. In the beginning, Disney World comprised a single park, Magic Kingdom, and two hotels. Epcot, Disney’s Hollywood Studios, and Disney’s Animal Kindom came later. Today, the four parks combined draw 47 million visitors annually and Magic Kingdom is the most-visited theme park in the world. Those numbers are a testament to Walt Disney, one of the greatest entertainers who ever lived. His genius was in satisfying our desire not just to escape but to be inspired. You can’t not be hopeful about world peace as you watch Israeli and Arab child-figurines sing and twirl in the Magic Kingdom ride It’s a Small World. You can’t help but be encouraged by Epcot’s environmentally conscious eco-greenhouse exhibit, Living with the Land, which showcases responsible agriculture. And if the corporate sponsor of Living with the Land happens to be Chiquita, which has a history of using highly toxic pesticides and violating workers’ rights, well, relax, have a good time, don’t overthink it. For dinner on our first evening, Marie and I walk from the Yacht Club to the shops and restaurants along Disney’s BoardWalk, where the atmosphere is 1920s Atlantic City—bare light bulbs, street performers, and a wooden walkway that runs along the lake. We could be at any charming, touristy waterfront resort. Dinner is at the Flying Fish Café, a contemporary seafood place with nary a cartoon character in sight. The Degustation of Flying Fish Artisanal Cheeses rivals any dégustation of artisanal cheeses I’ve enjoyed in New York; the Asian-inspired char-crusted yellowfin tuna is respectable; and there are some nice wine pairings. Marie awards the meal a nine on a scale of ten for Disney cuisine, and we agree it’s a six or seven in the real world. The sophisticated adult in me is pleased, and my inner child goes to bed ready for a day of fun. Good morning, Magic Kingdom! With the sun rising in a crystalline Disney sky, the Victorian-esque buildings along Main Street U.S.A., just inside the park’s entrance, are bathed in an ethereal golden glow. Barbers at the Harmony Barber Shop stand at the ready (they really do cut hair, and there’s a barbershop quartet, naturally). Gleaming Mickey merchandise is ready to be sold, and am I imagining it or do I detect a whiff of homemade snickerdoodles on the breeze? Marie carries a handbag acquired during a previous Disney vacation. It resembles a classic Marc Jacobs top-handle satchel, but with a pattern of tiny, colorful Minnie Mouse figures. Something inside me has definitely shifted overnight, because suddenly I want one. This morning we’re on an adult group tour called Keys to the Kingdom, a five-hour odyssey through off-limits areas of the park, including its mythical underground tunnels. Our guide is a young German woman inexplicably dressed in an equestrian outfit, with a velvet helmet and riding crop, and the tour is, in a word, exhaustive. If you are Disney-obsessed, it might be for you. If not, here are the highlights: Listen carefully to the dancing animatronic natives near the end of the Jungle Cruise ride. One of them clearly says, “I love disco.” A travel guide for grown-ups on the best hotels, restaurants, and activities in the park. In another clever inside joke, the entire resort is full of “hidden Mickeys”: stylized Mickey Mouse heads snuck into the metal scrollwork of gates, the tire treads of official vehicles, the arrangement of plates on a table in the Haunted Mansion, and so on. (It will become my obsession to spot them everywhere I go.) The tunnels employees use to get quickly around the park and to transport deliveries are not the dank catacombs I’d imagined. They’re rather prosaic industrial corridors, called Utilidors, and aren’t truly underground but on the “first floor” of the Magic Kingdom; the public part of the park starts on the “second floor.” What do they do with all of the garbage? Why, they suck it away through massive pneumatic tubes under the park. (Disney World is, not surprisingly, sparkling clean—the custodians even wear immaculate white uniforms.) As for pumping in a cookie smell, Disney does no such thing, our guide tells us, as we stand in the Utilidor under Main Street U.S.A. Then she indicates a small compressor above our heads. “But that doesn’t mean we didn’t try it once,” she says. At the end of the tour, we’re allowed to ask questions. Mine is: “Do people ever get caught having public hanky-panky in the park?” This has been nagging at me ever since I found out how many adults do Disney without kids. Aren’t some of them at least tempted to misbehave? The guide pretends not to hear. “Do people ever get frisky in the bushes?” I persist, like the reporter she doesn’t know I am. “No,” she says. I half expect her to smack me with her riding crop. But this is not a Fifty Shades of Disney moment. Not at all. The tour guide explains briskly that the park is too crowded for furtive sexcapades. I don’t entirely believe her. But it is true that the Magic Kingdom is so wholesome and earnest, I can’t imagine it inspiring much lewd behavior. After the tour, Marie and I are as giddy as middle-schoolers sprung from detention. Time for rides! I vote for Space Mountain, the extraordinary roller coaster that spins you around in the dark under a simulated galaxy of stars. Marie worries she’ll hurt her neck. We settle on Pirates of the Caribbean, the crowd-pleasing boat adventure. Since the 2006 addition of an animatronic Johnny Depp, Pirates has turned into the ride version of the Pirates of the Caribbean movie—which, in a Gordian knot of entertainment-industry synergy, was originally conceived as the movie version of the ride. After that it’s on to the fairy-tale-themed New Fantasyland, to the brand-new Under the Sea—Journey of the Little Mermaid, the ride version of the 1989 movie. Neither of these rides connects me to my inner child, just to my cynical, impatient adult who is rolling her eyes at the brazen marketing and irritated about having waited an hour in line for Under the Sea, which was a real disappointment. (In fairness, I admit I’m not the target demographic.) Then we pass the gift shop. This being New Fantasyland, it’s full of princess gear. Marie and I can’t resist ogling the tulle dresses and magic wands, and before we know it, we are buying matching pink crowns. We put them on, walk out giggling, and get in line for It’s a Small World. “Hello, Your Majesty,” the ride operator says to each of us, curtseying. We step into our boat, waving with queenly decorum. That evening, and again the following morning, we head to Epcot, the least cohesive of the Disney theme parks. More than twice the size of the Magic Kingdom, at 305 acres, Epcot is not the working, futuristic city Walt Disney imagined it would be. Nobody lives there. It’s an odd amalgam of attractions with rides that were once futuristic but are now amusingly retro—including Soarin’ and Living with the Land—and corporate-sponsored, children’s-museum-style exhibits on topics such as fire safety and money management. Epcot is probably best known for its World Showcase. There, visitors can stroll through re-creations of 11 different countries, each approximately the size of a few city blocks, with shops, restaurants, architecture, and “culture” reminiscent of the real place. As with all things Disney, appreciating the World Showcase takes a willful suspension of disbelief. The France area includes a 1:10 scale reproduction Eiffel Tower; Italy is a mashup of Venice, Florence, and Rome. Most peculiar of all is the ultra-patriotic American area, sandwiched between Italy and Japan. First you have to wrap your mind around visiting pretend America while actually in real America. Then you enter the supersize American Adventure hall, built in Georgian-ish style (though the bricks of its facade are made from real Georgia clay) and so excessively stately that I come to call it the American Hall of Americanness. Our packed itinerary leaves us no time to stay and see “We the People,” a 30-minute stage show starring an animatronic Ben Franklin and Mark Twain. Instead, we watch the Voices of Liberty, an a cappella group in nineteenth-century costume, sing a rendition of the national anthem that has me covered in goose bumps with my hand over my heart. Plaques bearing inspirational quotes from American patriots are arrayed under the imitation eighteenth-century rotunda. It’s all so stirring—until I end up in front of a quote from the far-right idol Ayn Rand. My inner child and I run for the exit. The number of cast members at Walt Disney World (making it the largest single-site employer in the United States) On the third morning of my Disney visit, I find myself in the center of a rope bridge (the rickety kind that straddles Third World gorges in adventure movies), looking down into a ravine filled with crocodiles that I’m certain are not set decorations. I am strapped into a safety vest and hooked to a steel cable, so there’s no chance of my falling into the hungry gullets below. But this feels pretty darn real, which might be why the Wild Africa Trek at Disney’s Animal Kingdom proves to be one of the most memorable parts of the trip. I’m in a group of eight on a mini safari, led by a pair of guides who take us on foot and in an open-sided truck through 100 acres of wetlands and grasslands. During the three-hour excursion, led by an appealing and peppy twentysomething duo who share lots of fun facts about the animals, we see grazing giraffes, snoozing cheetahs, and regal lions. About two hours in, we stop at a viewing platform for a simple lunch of cheese, cured meat, and dried fruit that is my favorite meal of the week. I’ve never been to Africa, so the small-scale safari seems authentic enough to me. So does Harambe, the theme park’s ersatz East African port village from which we “depart,” with its faux-dilapidated stucco colonial buildings with their faux-faded signs. My second hotel, the six-story Animal Kingdom Lodge, seems authentic enough, too. It has a rustic, airy lobby and an Africa-themed restaurant. My room overlooks a “savanna,” one of three ten-acre areas stocked with gazelles, zebras, and more giraffes. You can sit on the room’s private terrace in the quiet and survey the wildlife strolling just a couple of stories below. The night air smells of grass. Marie is transfixed, but I find my old self creeping back as I worry about the animals being always on display in this artificially moonlit landscape. While I am bothered by the weirdness of visiting all of these phony foreign countries, Marie has a different spin: Maybe, she says, people who come to fake Africa will be inspired to travel to real Africa. She posits that through movies such as Bambi, Walt Disney helped start the environmental movement by making baby boomer children care about talking animals. Perhaps in some small way, Disney, which makes a point to hire employees from the countries it re-creates, is fostering a greater communication between Americans and other cultures. The approximate number of outfits in Mickey's wardrobe. The approximate number of outfits in Minnie's wardrobe (the point: Mickey's closet is larger). The manager at Disney’s Grand Floridian Resort & Spa, Walt Disney World’s premiere property, is giddy with delight when he announces the good news at check-in: My husband and I are the hotel’s Family of the Day! We have been chosen at random for an upgraded room and access to the concierge floor, with its bounty of complimentary snacks. He even snaps our photo as we stroll up a red carpet that has been rolled out especially for us. Who doesn’t love special treatment? I think it’s all kind of nice. But if Marie was Tinker Bell, my husband is Grumpy. “This place is thoroughly inauthentic,” he mutters, as a lobby pianist breaks into what is probably the sixth rendition of “Beauty and the Beast” that I have heard in the past four days. My husband fiddles with the two large Disney buttons the manager had him pin on the lapel of his blazer. “Do we have to wear these to dinner?” Grumpy asks. I remind him that we are supposed to be immersing ourselves in the Disney experience. Which is how I end up at the fanciest restaurant in all of Walt Disney World, wearing a Prada dress and twin buttons that say “Disney’s Family of the Day!” and “Happy Anniversary!” Disney is big on cute storybook romance. Weddings and honeymoons are a significant business here. Couples wear bride-and-groom mouse-ear hats and Disney buttons announcing their relationship status. Grumpy and I have decided to celebrate our real wedding anniversary a few days early with dinner at Victoria & Albert’s, the award-winning and very expensive restaurant the company describes as “a tiny oasis of opulence.” Opulent it is: This time we’re transported to 1885 England by way of 1985 Las Vegas, with mirrors, dripping chandeliers, and swaths of brocade. (There’s a hidden Mickey in the carpet, in case you were wondering.) The waitstaff are attentive—perhaps too much so—detailing every last ingredient, every drop of wine, even the philosophy behind the bread and butter, as if they think this is the first time we’ve ever patronized such a swank joint. Afterward, we step outside for a short private boat ride into the middle of Seven Seas Lagoon to watch the Wishes Nighttime Spectacular fireworks show. Synchronized audio on board our little boat plays a sound track, a mélange of dialogue and music from classic Disney movies. The message is pure Disney: Anything you wish can come true, anything you dream is possible. We’re two skeptics in a skiff, and we turn to each other and ask, “Really? Anything anyone dreams can come true? Really?” It occurs to me that I have traveled to a foreign land after all. Walt Disney World—litter-free, poverty-free, with its industrious labor force, mannerly guests, and all-encompassing positivity—is Fantasy America, the America we all wish we lived in. It’s the America that Americans are nostalgic for. It is secular paradise. And it has never existed, not ever, except in Walt Disney’s imagination. And this, too, is the man’s genius: He found a way to satisfy our collective dream of a better country while relieving us of the burden of effecting true change. The garbage and disgruntled workers and urban sprawl of real America are a lot easier to bear if you can escape it all for a few days in Disney’s America. In the same way we gobble up Downton Abbey or Ralph Lauren’s vision of an elegant bygone era that didn’t quite exist, it’s a comfort to believe in Disney’s cuddly nation. It’s the America of our innocence. Before we became jaded. Before we had our first hard knock. Before we were taught to be responsible and to live in reality. But for me, at least, experience has won the battle with innocence. There’s just no going back. And yet…the following morning, our final day together at the resort, Grumpy and I head to Epcot for one last tour. After a quick tutorial, we step onto Segway scooters for a look at the theme park’s archetypal renderings of a Moroccan bazaar and a Japanese pagoda. Riding the Segways is a blast, and before long, Grumpy and I are laughing and zipping around like, well, kids. It would be impossible to maneuver one of these things on the packed, uneven, littered sidewalks of New York, out there in the real world. But Walt Disney World, with its perfect terrain on this perfect day, is the perfect place to ride. Illustrations by Eddie Guy

What is this witchcraft? DeskDock, now available on the Play Store, allows you to share your computer's keyboard and mouse with your Android device. If you've ever used Synergy, it's very close to that. What's the point of something like this, you may ask? The primary use the developer provided was to make Android development much easier. With this tool, you could work on an application on your computer, push it to your device, and test it without your hands ever leaving your keyboard. But there are plenty of other potential uses as well - you could use your Android tablet as another monitor to watch media on, for example. Read More Last week, CodeWeavers announced that after three years of development, a preview version of CrossOver for Android would be released. Why was I so excited? Because CrossOver allows you to run Windows programs on Mac and Linux, and they brought their expertise over to Android. After trying out the Preview version for a week (which you can sign up for here), I'm extremely impressed by its capabilities, despite some major limitations. Chromebooks started as just a portal to web apps, but more powerful extensions eventually made them a little more robust. Now, the Play Store is rolling out on Chromebooks to add a ton of new functionality. But... what about Windows apps? A company called CodeWeavers is tantalizingly close to making that happen thanks to the new Android support. So, we're talking about Windows on both Android and Chrome. As you can see from the image above, they are very, very excited about the prospect. Read More Remember way back in the golden days of earlier this month when we posted about possible upcoming desktop clients for the super-popular WhatsApp SMS alternative? Well the time has finally arrived, a whole nine days later. The company has announced on its official blog that the desktop versions are now available for Windows and Mac OS X. Sorry Linux users, you're stuck using the web client... but if it's any consolation, they look more or less identical. Read More WhatsApp has conquered the world of low-cost SMS alternatives, at least in the international market. The company's practically free system, which uses standard phone numbers and a text message-style interface, gained hundreds of millions of users before being acquired by Facebook for an amazing $19 billion. WhatsApp already offers a web interface for sending and receiving messages away from your phone, but it looks like something a bit more complex may be in the works. Read More For a while, desktop Google Drive's selective sync functionality has been rather, well, selective. You could only select top-level folders. This meant you could select all of your music, or all of your photos, but not a specific set of albums. Now that's changing. Read More There are many applications that aim to mirror your phone's screen on your computer, or let you control your phone from your computer, or even cast/mirror your phone to a display and connect a keyboard and mouse to control it. But none of these seems as simple as this latest idea from Lenovo. The LINK is a 32GB USB flash drive, but not only can it be plugged into your Windows (7, 8, 8.1, and 10) computer, it also has another USB 3.0 port on the other side where you plug in your phone's cable. First, this lets you use a flash drive and charge your phone simultaneously, saving you one USB port on your computer. Read More Windows has no idea what to do with that mountain of APK files you've probably downloaded from APK Mirror, which can make managing said mountain of files annoying. Apkshellext2 is a Windows shell extension that might make your life much easier, as it has mine. Just a few clicks and Windows Explorer will get much smarter. Read More João Dias, also known as joaomgcd on the Play Store, is one of those developers who are never, ever, content with the current capabilities of modern smartphones. He wants them to be more powerful, respond to more commands, allow more interactions, all from more interfaces. His AutoVoice app has been available for a while, allowing you to harness the OK Google interaction scheme to automate plenty of new actions and issue commands that Google's default algorithms don't yet understand. Now AutoVoice is getting a lil' sister app, an AutoVoice Chrome extension for your Windows, Mac, and Linux computers. Thanks to it, you can perform the same actions on your phone, but while sitting at your computer (or from another phone too), like taking screenshots, sending messages, hanging up on calls, and more. João has made a demo video to show you the possibilities. Read More AMIDuOS, a popular solution for running Android apps on Windows, has issued a major update today that brings users a full Lollipop virtual environment. The update, to version 2.0, is most notable for leaving the now very-dated world of 4.2 Jelly Bean. With it also comes support for 64-bit apps, the ART runtime, and better APIs and compatibility for hardware features such as Bluetooth 4.0. On the not-as-fun side, the lifetime license now costs $15, up from the prior version's $10 cost. A key difference between AMIDuOS and competitors like BlueStacks is that it is not merely an "app player," as BlueStacks brands itself. Read More

TransLogic acquired by CNC Holdings Published 2:41 pm, Friday, April 22, 2016 BAD AXE — TransLogic Auto Carriers, LLC has announced the acquisition of 53 percent ownership by CNC Holdings, LLC of West Bloomfield. TransLogic founder Lyn J. Tetreau, who holds the remaining 47 percent of shares, will continue as president of TransLogic, while Ricky N. Coley of CNC Holdings will serve in the new position of executive chairman. Coley brings over 20 years’ worth of background in supply chain and facility management, planning, and operations to the new management team, having run multi-billion dollar logistics operations for Ford and General Motors. Tetreau has many years of experience in sales management and car hauling operations. Both company leaders believe their combined, hands-on backgrounds, having represented original equipment auto manufacturers (OEMs) and suppliers alike, will ideally position company management to be more responsive and in tune with present and future customer needs. “We’re very excited to work with one another,” said Tetreau in an interview at the Huron Daily Tribune office Oct. 3. “Ricky is taking the company to even higher levels.” Tetreau said with Coley’s background with auto manufacturers, TransLogic will look even better in the eyes of the customers. Coley is pleased to have Tetreau as a business partner. “(Tetreau’s) leadership ability and experience have been phenomenal. I feel I got the better end of the deal,” Coley said. Tetreau and Coley were introduced to one another by acquaintances of theirs who thought Tetreau and Coley would make good business partners. They were right. During their meeting with the Tribune, Tetreau and Coley talked about the synergy between them. “Our visions align,” Coley said. The two TransLogic owners are excited about the possibilities that lie ahead, including providing additional local jobs. Tetreau said in the next two years, the plan is to double the size of the current staff at the Bad Axe corporate office, located at 210 Pigeon Road. Currently, about 50 people work at this office. Coley and Tetreau are working to bring in great opportunities for TransLogic. The company has bid on $130 million worth of business in the last 30 days. With 2007 sales of approximately $40 million, TransLogic provides local and long-haul auto transportation services to major car manufacturers, including General Motors, Ford, Chrysler, Honda, VWA, Subaru, Kia and others. TransLogic provides national central vehicle dispatch with facilities in Detroit, Colorado, Florida, Virginia, Indiana, and Massachusetts. Along with auto transit, TransLogic facilitates vehicle distribution by offering vehicle storage with marshalling to manufacturers, as well as mobile management response services. TransLogic Auto Carriers, LLC started as Showtime Motors and Transport in 1999. At that time, the business also was a car dealership. Showtime then merged with Road One, and in November 2002 the business became TransLogic. According to Tetreau, he entered the auto transportation business when he managed a car dealership in northern Michigan and purchased a three-car carrier to haul his lot cars. A short time later, he had a customer offer to purchase the carrier, and for a small difference he was able to purchase a seven-car carrier. Tetreau then started delivering large numbers of vehicles for a northern Michigan auto dealer every week. Tetreau purchased a second truck and the dealer gave him all of his freight, including other states. Tetreau then purchased two more trucks and solicited more customers, eventually building to 28 trucks over a couple of years. TransLogic’s main focus is on security, on-time deliveries and low incidents of defects. The objective is to be the preferred carrier of choice of automobile transportation and related logistics services for its customers, which include the Big Three auto manufacturers. TransLogic delivers to dealerships, auctions, railhead facilities and ports. “Our customers (the OEMs) are focused not only on streamlining their operations and cutting their bottom-line costs, but also on supplier innovations that will help them in more efficient distribution of their vehicles, getting the driving-public-desired, OEM-profitable vehicles to market first,” Coley stated in a press release. “At TransLogic, we are committed to increasing our capabilities by strategic acquisitions and controlled organic growth. We are also committed to bringing the latest in reliable and timely logistics processes for vehicle delivery using cost-effective technologies.” The company maintains 80 staff employees nationwide in addition to over 300 transport drivers. Tetreau and Coley believe TransLogic is well positioned to maintain — and eclipse — its past success. “The rest of 2008 is our prep for the future. We’re fine tuning everything,” Tetreau said. “In 2009, the rubber will meet the road,” Coley said. Traci L. Weisenbach • (989) 269-6461 • email@example.com

Salesforce org migrations often come about as a result of an acquisition, or a company is simply looking to have better synergy across multiple business units (or operating companies). There are many benefits to having a single Salesforce instance versus two (or more) – from centralized user administration, a common master database available to sales and marketing, a single connection point for your integrations, and the ability to roll-up your data to a shared set of dashboards for management. The reality is that Salesforce Org Migrations are very complex initiatives. The good news is, unlike other data migrations, the databases being merged share the same architecture. However, due to the vast amount of customizations that can be present in either Salesforce instance, merging the two databases requires a lot of planning and coordination. Things you’ll need to consider when merging two (or more) instances of Salesforce.com: - Profiles for users and user licensing options - Security settings, record and folder access - Multiple record types, business processes and page layouts - Assignment Rules, Auto-Response Rules, Escalation Rules, Workflow Rules, Validation Rules, Apex triggers and other custom code - Impact to existing integrations - System constraints and governor limits (e.g. total number of custom objects, fields, tabs, rules, etc.) - Impact to Territory Management and Forecasting - If your company is international, foreign language and multi-currency - Migrating existing email templates, documents, reports and dashboards - How to handle duplicate records, record ownership, inactive users Fortunately we can help you through these hurdles and guide you through the process to have a successful migration. For a deep dive on the process of merging two or more Salesforce orgs, see our customer presentation on SlideShare. Other Salesforce Services