bluuebunny/crossref_metadata_2025 huggingface dataset:
NTID International Symposium on Technology and Deaf Education
Authors: Cavender Anna , Ladner Richard E.
Published: November 2010

The International Symposium on Technology and Deaf Education at the National Technical Institute for the Deaf (NTID) at Rochester Institute of Technology is a bi-yearly (occurring once every two years) conference that attracts professionals, educators, technologists, and researchers who are interested in, developing for, and affected by technology for the education of deaf and hard of hearing students. This mixture of professionals leads to many interesting discussions, presentations, and exhibits with the purpose of dissemination of full research projects and best practices. This year the symposium, June 21--23, 2010, accepted 64 papers each with presentations 45 minutes long, 15 minutes of which were devoted to question and answer, and discussion. Presenters were chosen to reflect the current issues and solutions in both educational and access technologies. The symposium is also a great venue to share works-in-progress, current trends, and state of the art technology shown by 28 posters and 11 commercial exhibits. Over 300 people attended from 17 different countries including presentations by participants from Japan, Thailand, Canada, China, Czech Republic, Russia, Philippines, Poland, and Rwanda.
Shareholder Voting and Corporate Governance
Authors: Yermack David
Published: November 2010

This article reviews recent research into corporate voting and elections. Regulatory reforms have given shareholders more voting power in the election of directors and in executive compensation issues. Shareholders use voting as a channel of communication with boards of directors, and protest voting can lead to significant changes in corporate governance and strategy. Some investors have embraced innovative empty voting strategies for decoupling voting rights from cash flow rights, enabling them to mount aggressive programs of shareholder activism. Market-based methods have been used by researchers to establish the value of voting rights and show how this value can vary in different settings.
Bayesian Portfolio Analysis
Authors: Avramov Doron , Zhou Guofu
Published: November 2010

This paper reviews the literature on Bayesian portfolio analysis. Information about events, macro conditions, asset pricing theories, and security-driving forces can serve as useful priors in selecting optimal portfolios. Moreover, parameter uncertainty and model uncertainty are practical problems encountered by all investors. The Bayesian framework neatly accounts for these uncertainties, whereas standard statistical models often ignore them. We review Bayesian portfolio studies when asset returns are assumed both independently and identically distributed as well as predictable through time. We cover a range of applications, from investing in single assets and equity portfolios to mutual and hedge funds. We also outline challenges for future work.
CEO Compensation
Authors: Frydman Carola , Jenter Dirk
Published: November 2010

This paper surveys the recent literature on CEO compensation. The rapid rise in CEO pay over the past 30 years has sparked an intense debate about the nature of the pay-setting process. Many view the high level of CEO compensation as the result of powerful managers setting their own pay. Others interpret high pay as the result of optimal contracting in a competitive market for managerial talent. We describe and discuss the empirical evidence on the evolution of CEO pay and on the relationship between pay and firm performance since the 1930s. Our review suggests that both managerial power and competitive market forces are important determinants of CEO pay, but that neither approach is fully consistent with the available evidence. We briefly discuss promising directions for future research.
Hypotonic swelling-induced activation of PKN1 mediates cell survival in cardiac myocytes
Authors: Kajimoto Katsuya , Shao Dan , Takagi Hiromitsu , Maceri Gregorio , Zablocki Daniela , Mukai Hideyuki , Ono Yoshitaka , Sadoshima Junichi
Published: October 2010

Hypotonic cell swelling in the myocardium is induced by pathological conditions, including ischemia-reperfusion, and affects the activities of ion transporters/channels and gene expression. However, the signaling mechanism activated by hypotonic stress (HS) is not fully understood in cardiac myocytes. A specialized protein kinase cascade, consisting of Pkc1 and MAPKs, is activated by HS in yeast. Here, we demonstrate that protein kinase N1 (PKN1), a serine/threonine protein kinase and a homolog of Pkc1, is activated by HS (67% osmolarity) within 5 min and reaches peak activity at 60 min in cardiac myocytes. Activation of PKN1 by HS was accompanied by Thr774phosphorylation and concomitant activation of PDK1, a potential upstream regulator of PKN1. HS also activated RhoA, thereby increasing interactions between PKN1 and RhoA. PP1 (10−5M), a selective Src family tyrosine kinase inhibitor, significantly suppressed HS-induced activation of RhoA and PKN1. Constitutively active PKN1 significantly increased the transcriptional activity of Elk1-GAL4, an effect that was inhibited by dominant negative MEK. Overexpression of PKN1 significantly increased ERK phosphorylation, whereas downregulation of PKN1 inhibited HS-induced ERK phosphorylation. Downregulation of PKN1 and inhibition of ERK by U-0126 both significantly inhibited the survival of cardiac myocytes in the presence of HS. These results suggest that a signaling cascade, consisting of Src, RhoA, PKN1, and ERK, is activated by HS, thereby promoting cardiac myocyte survival.
Mechanisms related to NO-induced motility in differentiated rat aortic smooth muscle cells
Authors: Pu Qinghua , Zhuang Daming , Thakran Shalini , Hassid Aviv
Published: October 2010

Nitric oxide (NO) is thought to play an important role as an inhibitor of vascular cell proliferation, motility, and neointima formation. This effect is mediated, in part, via the upregulation of protein tyrosine phosphatase (PTP)1B. Conversely, studies have reported that in presumably hyperinsulinemic mice fed a high-fat diet, NO enhances vascular remodeling, whereas a deficit of NO attenuates vascular remodeling. We have reported that in differentiated cultured smooth muscle cells treated with insulin, NO induces a motogenic effect that is dependent on Src homology-2 domain PTP 2 (SHP2) upregulation. In the present study, we describe novel mechanisms relevant to the motogenic effect of NO. Treatment of cultured cells with the selective angiontensin type 1 receptor antagonist losartan, but not with the selective angiotensin type 2 receptor antagonist PD-123319, blocked the comotogenic capacity of NO and insulin. Insulin and NO increased the secretion of ANG II into the culture media by 2- and 2.5-fold ( P < 0.05), respectively, whereas treatment of cells with ANG II uncovered the motogenic effect of NO (1.4-fold above control, P < 0.05) and decreased the levels of PTP1B to 45% of control ( P < 0.05). Suppression of PTP1B function was sufficient to uncover the motogenic effect of NO. The capacity of insulin to suppress PTP1B activity was blocked by losartan, implicating ANG II function in mediating this effect. Both insulin and ANG II induced the upregulation of phosphatidyl inositol 3-kinase (PI3K)-δ by two- to threefold ( P < 0.05), and this effect was both necessary and sufficient to uncover NO-induced motogenesis. Finally, suppression of PTP1B function potentiated, whereas overexpression of PTP1B inhibited, SHP2-induced motogenesis. These results support the hypothesis that the comotogenic effect of insulin and NO occurs via an ANG II-mediated effect involving the suppression of PTP1B and upregulation of PI3K-δ and SHP2.
Accurate estimation of entropy in very short physiological time series: the problem of atrial fibrillation detection in implanted ventricular devices
Authors: Lake Douglas E. , Moorman J. Randall
Published: October 2010

Entropy estimation is useful but difficult in short time series. For example, automated detection of atrial fibrillation (AF) in very short heart beat interval time series would be useful in patients with cardiac implantable electronic devices that record only from the ventricle. Such devices require efficient algorithms, and the clinical situation demands accuracy. Toward these ends, we optimized the sample entropy measure, which reports the probability that short templates will match with others within the series. We developed general methods for the rational selection of the template length m and the tolerance matching r. The major innovation was to allow r to vary so that sufficient matches are found for confident entropy estimation, with conversion of the final probability to a density by dividing by the matching region volume, 2 r m. The optimized sample entropy estimate and the mean heart beat interval each contributed to accurate detection of AF in as few as 12 heartbeats. The final algorithm, called the coefficient of sample entropy (COSEn), was developed using the canonical MIT-BIH database and validated in a new and much larger set of consecutive Holter monitor recordings from the University of Virginia. In patients over the age of 40 yr old, COSEn has high degrees of accuracy in distinguishing AF from normal sinus rhythm in 12-beat calculations performed hourly. The most common errors are atrial or ventricular ectopy, which increase entropy despite sinus rhythm, and atrial flutter, which can have low or high entropy states depending on dynamics of atrioventricular conduction.
Phosphorylation of VE-cadherin controls endothelial phenotypes via p120-catenin coupling and Rac1 activation
Authors: Hatanaka Kunihiko , Simons Michael , Murakami Masahiro
Published: October 2010

To establish the role of vascular endothelial (VE)-cadherin in the regulation of endothelial cell functions, we investigated the effect of phosphorylation of a VE-cadherin site sought to be involved in p120-catenin binding on vascular permeability and endothelial cell migration. To this end, we introduced either wild-type VE-cadherin or Y658 phosphomimetic (Y658E) or dephosphomimetic (Y658F) VE-cadherin mutant constructs into an endothelial cell line (rat fat pad endothelial cells) lacking endogenous VE-cadherin. Remarkably, neither wild-type- nor Y658E VE-cadherin was retained at cell-cell contacts because of p120-catenin preferential binding to N-cadherin, resulting in the targeting of N-cadherin to cell-cell junctions and the exclusion of VE-cadherin. However, Y658F VE-cadherin was able to bind p120-catenin and to localize at adherence junctions displacing N-cadherin. This resulted in an enhanced barrier function and a complete abrogation of Rac1 activation and lamellipodia formation, thereby inhibiting cell migration. These findings demonstrate that VE-cadherin, through the regulation of Y658 phosphorylation, competes for junctional localization with N-cadherin and controls vascular permeability and endothelial cell migration.
2-Aminoethoxydiphenyl borate blocks electrical coupling and inhibits voltage-gated K+channels in guinea pig arteriole cells
Authors: Ma Ke-Tao , Guan Bing-Cai , Yang Yu-Qin , Nuttall Alfred L. , Jiang Zhi-Gen
Published: October 2010

2-Aminoethoxydiphenyl borate (2-APB) analogs are potentially better vascular gap junction blockers than others widely used, but they remain to be characterized. Using whole cell and intracellular recording techniques, we studied the actions of 2-APB and its potent analog diphenylborinic anhydride (DPBA) on vascular smooth muscle cells (VSMCs) and endothelial cells in situ of or dissociated from arteriolar segments of the cochlear spiral modiolar artery, brain artery, and mesenteric artery. We found that both 2-APB and DPBA reversibly suppressed the input conductance ( Ginput) of in situ VSMCs (IC50≈ 4–8 μM). Complete electrical isolation of the recorded VSMC was achieved at 100 μM. A similar gap junction blockade was observed in endothelial cell tubules of the spiral modiolar artery. Similar to the action of 18β-glycyrrhetinic acid (18β-GA), 2-APB and DPBA depolarized VSMCs. In dissociated VSMCs, 2-APB and DPBA inhibited the delayed rectifier K+current ( IK) with an IC50of ∼120 μM in the three vessels but with no significant effect on Ginputor the current-voltage relation between −140 and −40 mV. 2-APB inhibition of IKwas more pronounced at potentials of ≤20 mV than at +40 mV and more marked on the fast component than on the slow component, which was mimicked by 4-aminopyridine but not by tetraethylammonium, nitrendipine, or charybdotoxin. In contrast, 18β-GA caused a linear inhibition of IKbetween 0 to +40 mV, which was similar to the action of tetraethylammonium or charybdotoxin. Finally, the 2-APB-induced inhibition of electrical coupling and IKwas not affected by the inositol 1,4,5-trisphosphate receptor antagonist xestospongin C. We conclude that 2-APB analogs are a class of potent and reversible vascular gap junction blockers with a weak side effect of voltage-gated K+channel inhibition. They could be gap junction blockers superior to 18β-GA only when Ca2+-actived K+channel inhibition by the latter is a concern but inositol 1,4,5-trisphosphate receptor and voltage-gated K+channel inhibitions are not.
Reduced conduction reserve in the diabetic rat heart: role of iPLA2activation in the response to ischemia
Authors: Rahnema Parisa , Shimoni Yakhin , Nygren Anders
Published: October 2010

Hearts from streptozotocin (STZ)-induced diabetic rats have previously been shown to have impaired intercellular electrical coupling, due to reorganization (lateralization) of connexin43 proteins. Due to the resulting reduction in conduction reserve, conduction velocity in diabetic hearts is more sensitive to conditions that reduce cellular excitability or intercellular electrical coupling. Diabetes is a known risk factor for cardiac ischemia, a condition associated with both reduced cellular excitability and reduced intercellular coupling. Activation of Ca2+-independent phospholipase A2(iPLA2) is known to be part of the response to acute ischemia and may contribute to the intercellular uncoupling by causing increased levels of arachidonic acid and lysophosphatidyl choline. Normally perfused diabetic hearts are known to exhibit increased iPLA2activity and may thus be particularly sensitive to further activation of these enzymes. In this study, we used voltage-sensitive dye mapping to assess changes in conduction velocity in response to acute global ischemia in Langendorff-perfused STZ-induced diabetic hearts. Conduction slowing in response to ischemia was significantly larger in STZ-induced diabetic hearts compared with healthy controls. Similarly, slowing of conduction velocity in response to acidosis was also more pronounced in STZ-induced diabetic hearts. Inhibition of iPLA2activity using bromoenol lactone (BEL; 10 μM) had no effect on the response to ischemia in healthy control hearts. However, in STZ-induced diabetic hearts, BEL significantly reduced the amount of conduction slowing observed beginning 5 min after the onset of ischemia. BEL treatment also significantly increased the time to onset of sustained arrhythmias in STZ-induced diabetic hearts but had no effect on the time to arrhythmia in healthy control hearts. Thus, our results suggest that iPLA2activation in response to acute ischemia in STZ-induced diabetic hearts is more pronounced than in control hearts and that this response is a significant contributor to arrhythmogenic conduction slowing.
Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers
Authors: de Diego Carlos , Chen Fuhua , Xie Yuanfang , Pai Rakesh K. , Slavin Leonid , Parker John , Lamp Scott T. , Qu Zhilin , Weiss James N. , Valderrábano Miguel
Published: October 2010

Anisotropy can lead to unidirectional conduction block that initiates reentry. We analyzed the mechanisms in patterned anisotropic neonatal rat ventricular myocyte monolayers. Voltage and intracellular Ca (Cai) were optically mapped under the following conditions: extrastimulus (S1S2) testing and/or tetrodotoxin (TTX) to suppress Na current availability; heptanol to reduce gap junction conductance; and incremental rapid pacing. In anisotropic monolayers paced at 2 Hz, conduction velocity (CV) was faster longitudinally than transversely, with an anisotropy ratio [AR = CVL/CVT, where CVL and CVT are CV in the longitudinal and transverse directions, respectively], averaging 2.1 ± 0.8. Interventions decreasing Na current availability, such as S1S2 pacing and TTX, slowed CVL and CVT proportionately, without changing the AR. Conduction block preferentially occurred longitudinal to fiber direction, commonly initiating reentry. Interventions that decreased gap junction conductance, such as heptanol, decreased CVT more than CVL, increasing the AR and causing preferential transverse conduction block and reentry. Rapid pacing resembled the latter, increasing the AR and promoting transverse conduction block and reentry, which was prevented by the Cai chelator 1,2-bis oaminophenoxy ethane- N, N, N′, N′-tetraacetic acid (BAPTA). In contrast to isotropic and uniformly anisotropic monolayers, in which reentrant rotors drifted and self-terminated, bidirectional anisotropy (i.e., an abrupt change in fiber direction exceeding 45°) caused reentry to anchor near the zone of fiber direction change in 77% of monolayers. In anisotropic monolayers, unidirectional conduction block initiating reentry can occur longitudinal or transverse to fiber direction, depending on whether the experimental intervention reduces Na current availability or decreases gap junction conductance, agreeing with theoretical predictions.
Molecular Characterization of Glycopeptide-Resistant Enterococci from Hospitals of the Picardy Region (France)
Authors: Biendo M. , Adjidé C. , Castelain S. , Belmekki M. , Rousseau F. , Slama M. , Ganry O. , Schmit J. L. , Eb F.
Published: October 2010

We studied 138 glycopeptide-resistant enterococci (GRE) strains, consisting of 131 glycopeptide-resistantEnterococcus faecium(GREfm) and 7 glycopeptide-resistantEnterococcus faecalis(GREfs). The GREfm strains were resistant to penicillin, ampicillin, vancomycin, and teicoplanin, while the GREfs strains were only resistant to vancomycin and teicoplanin. Thevan Agene was the only glycopeptide determinant present in all GRE isolates investigated. Genes coding for Hyl and Hyl+ Esp were detected in 39 (29.8%) and 92 (70.2%) of the 131 GREfm isolates, respectively. Three of the 7 GREfs were positive forgelE+asa 1genes, 3 forgel Egene, and 1 forasa 1gene. The genetic relationship between the 138 GRE was analyzed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). GREfm isolates were clustered in a single genogroup (pulsotype A), and GREfs were clustered in six genogroups (pulsotypes B-G). Among the isolates investigated by MLST, only 18 PCR products were sequenced (12E. faeciumand 6E. faecalis), and 9 sequence types (STs) were identified.
Diesel Engine Exhaust Initiates a Sequence of Pulmonary and Cardiovascular Effects in Rats
Authors: Kooter Ingeborg M. , Gerlofs-Nijland Miriam E. , Boere A. John F. , Leseman Daan L. A. C. , Fokkens Paul H. B. , Spronk Henri M. H. , Frederix Kim , ten Cate Hugo , Knaapen Ad M. , Vreman Hendrik J. , Cassee Flemming R.
Published: October 2010

This study was designed to determine the sequence of events leading to cardiopulmonary effects following acute inhalation of diesel engine exhaust in rats. Rats were exposed for 2 h to diesel engine exhaust (1.9 mg/m3), and biological parameters related to antioxidant defense, inflammation, and procoagulation were examined after 4, 18, 24, 48, and 72 h. This in vivo inhalation study showed a pulmonary anti-oxidant response (an increased activity of the anti-oxidant enzymes glutathione peroxidase and superoxide dismutase and an increase in heme oxygenase-1 protein, heme oxygenase activity, and uric acid) which precedes the inflammatory response (an increase in IL-6 and TNF-α). In addition, increased plasma thrombogenicity and immediate anti-oxidant defense gene expression in aorta tissue shortly after the exposure might suggest direct translocation of diesel engine exhaust components to the vasculature but mediation by other pathways cannot be ruled out. This study therefore shows that different stages in oxidative stress are not only affected by dose increments but are also time dependent.
Lipid Metabolism and Cardiovascular Risk in HIV-1 Infection and HAART: Present and Future Problems
Authors: Melzi Sara , Carenzi Laura , Cossu Maria Vittoria , Passerini Simone , Capetti Amedeo , Rizzardini Giuliano
Published: October 2010

Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date.
Psychological Stress Alters Ultrastructure and Energy Metabolism of Masticatory Muscle in Rats
Authors: Chen Yong-Jin , Huang Fei , Zhang Min , Shang Hai-Yan
Published: October 2010

To investigate the effects of psychological stress on the masticatory muscles of rats, a communication box was applied to induce the psychological stress (PS) in rats. The successful establishment of psychological stimulation was confirmed by elevated serum levels of adrenocorticotropic hormone (ACTH) and changed behaviors in the elevated plusmaze apparatus. The energy metabolism of the bilateral masseter muscles was tested via chemocolorimetric analysis, whereas muscle ultrastructure was assessed by electron microscopy. In comparison to the control group, the PS group showed evidence of swollen mitochondria with cristae loss and reduced matrix density in the masticatory muscles after three weeks of stimulation; after five weeks of stimulation, severe vacuolar changes to the mitochondria were observed. Increased vascular permeability of the masticatory muscle capillaries was found in the five-week PS rats. In addition, there was decreased activity ofNa+-K+ATPase andCa2+-ATPase and a simultaneous increase in the activity of lactate dehydrogenase and lactic acid in the masticatory muscles of PS rats. Together, these results indicate that psychological stress induces alterations in the ultrastructure and energy metabolism of masticatory muscles in rats.
Retroperitoneal Abscess: A Rare Localization of Tubercular Infection
Authors: Karoui Sami , Bibani Norsaf , Ouaz Afef , Serghini Meriem , Chebbi Faouzi , Nouira Kais , Chelly Ines , Boubaker Jalel , Ben Safta Zoubeir , Menif Emna , Zitouna Moncef , Filali Azza
Published: October 2010

Incidence of tuberculosis infection has considerably increased during the past 20 years due to the HIV pandemic and continues to be one of the most prevalent and deadly infections worldwide. Extrapulmonary tuberculosis lacks specific clinical manifestation and can mimic many diseases. It can invade neighbouring tissue and form a big cyst with manifesting clinical symptoms. We describe a rare case of 31-year-old immunocompetent man affected by a retroperitoneal abscess secondary to tubercular infection. Exploratory laparotomy and histopathological examinations of tissue were required for achieving diagnosis of tuberculosis. No pulmonary or spinal involvement was identified. The patient was successfully treated with standard four-drug antitubercular therapy.
Analysis of Reverse-Bias Leakage Current Mechanisms in Metal/GaN Schottky Diodes
Authors: Pipinys P. , Lapeika V.
Published: October 2010

Temperature-dependent reverse-bias current-voltage characteristics obtained by other researchers for Schottky diodes fabricated on GaN are reinterpreted in terms of phonon-assisted tunneling (PhAT) model. Temperature dependence of reverse-bias leakage current is shown could be caused by the temperature dependence of electron tunneling rate from traps in the metal-semiconductor interface to the conduction band of semiconductor. A good fit of experimental data with the theory is received in a wide temperature range (from 80 K to 500 K) using for calculation the effective mass of 0.222 . and for the phonon energy the value of 70 meV. The temperature and bias voltages dependences of an apparent barrier height (activation energy) are also explicable in the framework of the PhAT model.
In‐Medium Effects in the Holographic Quark‐Gluon Plasma
Authors: Rust Felix
Published: October 2010

We use the gauge/gravity duality to investigate various properties of strongly coupled
gauge theories, which we interpret as models for the quark‐gluon plasma (QGP). In particular,
we use variants of the D3/D7 setup as an implementation of the top‐down approach of connecting
string theory with phenomenologically relevant gauge theories.
We focus on the effects of finite temperature and finite density on fundamental matter in the
holographic quark‐gluon plasma, which we model as the 𝒩 = 2 hypermultiplet in addition to the
𝒩 = 4 gauge multiplet of supersymmetric Yang‐Mills theory.
We use a setup in which we can describe the holographic plasma at finite temperature and either
baryon or isospin density and investigate the properties of the system from three different viewpoints.
(i) We study meson spectra. Our observations at finite temperature and particle density are in
qualitative agreement with phenomenological models and experimental observations. They agree
with previous publications in the according limits.
(ii) We study the temperature and density dependence of transport properties of fundamental
matter in the QGP. In particular, we obtain diffusion coefficients. Furthermore, in a kinetic model we
estimate the effects of the coupling strength on meson diffusion and therewith equilibration processes
in the QGP.
(iii) We observe the effects of finite temperature and density on the phase structure of fundamental
matter in the holographic QGP. We trace out the phase transition lines of different phases in the
phase diagram.
Adiponectin and Leptin Metabolic Biomarkers in Chinese Children and Adolescents
Authors: Mi Jie , Munkonda Mercedes Nancy , Li Ming , Zhang Mei-Xian , Zhao Xiao-Yuan , Fouejeu Ponce Cedric Wamba , Cianflone Katherine
Published: October 2010

Objective. To evaluate leptin and adiponectin as biomarkers of metabolic syndrome (MS) risk factors even in nonobese children/adolescents.Methods. Serum leptin, adiponectin, leptin:adiponectin ratio, lipids, glucose, and insulin concentrations as well as body size parameters and pubertal development were evaluated in a large population of Chinese children/adolescents (n=3505, 6–18 years, 1722 girls and 1783 boys).Results. Leptin concentration increased while adiponectin decreased with obesity, both were influenced by pubertal development. Central obesity had an additive effect on leptin levels (above obesity alone). Leptin/adiponectin increased 8.4-fold and 3.2-fold in overweight/obesity, and 15.8- and 4.5-fold with obesity plus MS, in early and late puberty, respectively. Even in normal weight children/adolescents, higher leptin and lower adiponectin concentrations associated with increased risk profile. Conversely, overweight/obese with lower leptin or higher adiponectin concentrations had a less compromised metabolic profile.Conclusion. Leptin, adiponectin, and leptin:adiponectin ratio are informative biomarkers for obesity, central obesity, MS, and abnormal metabolic profile even in normal weight children/adolescents.
A Transgenic Mouse Model for Studying the Role of the ParathyroidHormone‐Related Protein System in Renal Injury
Authors: Bosch Ricardo J. , Ortega Arantxa , Izquierdo Adriana , Arribas Ignacio , Bover Jordi , Esbrit Pedro
Published: October 2010

Parathyroid hormone‐ (PTH‐) related protein (PTHrP) and its receptor, the PTH1 receptor (PTH1R), are widely expressed in the kidney, where PTHrP exerts a modulatory action on renal function. PTHrP is known to be upregulated in several experimental nephropathies such as acute renal failure (ARF), obstructive nephropathy (ON) as well as diabetic nephropathy (DN). In this paper, we will discuss the functional consequences of chronic PTHrP overexpression in the damaged kidney using a transgenic mouse strain overexpressing PTHrP in the renal proximal tubule. In both ARF and ON, PTHrP displays proinflammatory and profibrogenic actions including the induction of epithelia to mesenquima transition. Moreover, PTHrP participates in the mechanisms of renal hypertrophy as well as proteinuria in experimental DN. Angiotensin II (Ang II), a critical factor in the progression of renal injury, appears to be, at least in part, responsible for endogenous PTHrP upregulation in these pathophysiological settings. These findings provide novel insights into the well‐known protective effects of Ang II antagonists in renal diseases, paving the way for new therapeutic approaches.
Targeted Therapy of Ewing's Sarcoma
Authors: Subbiah Vivek , Anderson Pete
Published: October 2010

Refractory and/or recurrent Ewing's sarcoma (EWS) remains a clinical challenge because the disease's resistance to therapy makes it difficult to achieve durable results with standard treatments that include chemotherapy, radiation, and surgery. Recently, insulin-like-growth-factor-1-receptor (IGF1R) antibodies have been shown to have a modest single-agent activity in EWS. Patient selection using biomarkers and understanding response and resistance mechanisms in relation to IGF1R and mammalian target of rapamycin pathways are areas of active research. Since EWS has a unique tumor-specific EWS-FLI1 t(11;22) translocation and oncogenic fusion protein, inhibition of EWS-FLI1 transcription, translation, and/or protein function may be key to eradicating EWS at the stem-cell level. Recently, a small molecule that blocks the protein-protein interaction of EWS-FLI1 with RNA helicase A has been shown in preclinical models to inhibit EWS growth. The successful application of this first-in-class protein-protein inhibitor in the clinic could become a model system for translocation-associated cancers such as EWS.
Electrodeposition of Nanometer-Sized Ferric Oxide Materials in Colloidal Templates for Conversion of Light to Chemical Energy
Authors: Gardner James M. , Kim Su , Searson Peter C. , Meyer Gerald J.
Published: October 2010

Colloidal crystal templates were prepared by gravitational sedimentation of 0.5 micron polystyrene particles onto fluorine-doped tin oxide (FTO) electrodes. Scanning electron microscopy (SEM) shows that the particles were close packed and examination of successive layers indicated a predominantly face-centered-cubic (fcc) crystal structure where the direction normal to the substrate surface corresponds to the (111) direction. Oxidation of aqueous ferrous solutions resulted in the electrodeposition of ferric oxide into the templates. Removal of the colloidal templates yielded ordered macroporous electrodes (OMEs) that were the inverse structure of the colloidal templates. Current integration during electrodeposition and cross-sectional SEM images revealed that the OMEs were about 2 μm thick. Comparative X-ray diffraction and infrared studies of the OMEs did not match a known phase of ferric oxide but suggested a mixture of goethite and hematite. The spectroscopic properties of the OMEs were insensitive to heat treatments at300∘C. The OMEs were utilized for photoassisted electrochemical oxidation. A sustained photocurrent was observed from visible light in aqueous photoelectrochemical cells. Analysis of photocurrent action spectra revealed an indirect band gap of 1.85 eV. Addition of formate to the aqueous electrolytes resulted in an approximate doubling of the photocurrent.
Overexpression of Tumor Vascular Endothelial Growth Factor A May Portend an Increased Likelihood of Progression in a Phase II Trial of Bevacizumab and Erlotinib in Resistant Ovarian Cancer
Authors: Chambers Setsuko K. , Clouser Mary C. , Baker Amanda F. , Roe Denise J. , Cui Haiyan , Brewer Molly A. , Hatch Kenneth D. , Gordon Michael S. , Janicek Mike F. , Isaacs Jeffrey D. , Gordon Alan N. , Nagle Raymond B. , Wright Heather M. , Cohen Janice L. , Alberts David S.
Published: November 2010

Purpose: This phase II trial evaluated bevacizumab plus erlotinib in platinum-resistant ovarian cancer; exploratory biomarker analyses, including that of tumor vascular endothelial growth factor A (VEGF-A), were also done.

Experimental Design: Forty heavily pretreated patients received erlotinib (150 mg/d orally) and bevacizumab (10 mg/kg i.v.) every 2 weeks until disease progression. Primary end points were objective response rate and response duration; secondary end points included progression-free survival (PFS), toxicity, and correlations between angiogenic protein levels, toxicity, and efficacy.

Results: Grade 3 toxicities included skin rash (n = 6), diarrhea (n = 5), fatigue (n = 4), and hypertension (n = 3). Grade 4 toxicities were myocardial infarction (n = 1) and nasal septal perforation (n = 1). Only one grade 3 fistula and one grade 2 bowel perforation were observed. Nine (23.1%) of 39 evaluable patients had a response (median duration, 36.1+ weeks; one complete response), and 10 (25.6%) patients achieved stable disease, for a disease control rate of 49%. Median PFS was 4 months, and 6-month PFS was 30.8%. Biomarker analyses identified an association between tumor cell VEGF-A expression and progression (P = 0.03); for every 100-unit increase in the VEGF-A score, there was a 3.7-fold increase in the odds of progression (95% confidence interval, 1.1-16.6).

Conclusions: Bevacizumab plus erlotinib in heavily pretreated ovarian cancer patients was clinically active and well tolerated. Erlotinib did not seem to contribute to efficacy. Our study raises the intriguing possibility that high levels of tumor cell VEGF-A, capable of both autocrine and paracrine interactions, are associated with resistance to bevacizumab, emphasizing the complexity of the tumor microenvironment. Clin Cancer Res; 16(21); 5320–8. ©2010 AACR.
Phenotypic Variation in a Large Family with Autosomal Dominant Hypocalcaemia
Authors: Sørheim J.I. , Husebye E.S. , Nedrebø B.G. , Svarstad E. , Lind J. , Boman H. , Løvås K.
Published: November 2010

Background/Aims: Autosomal dominant hypocalcaemia (ADH) is caused by activating mutations in the calcium- sensing receptor (CASR). We aimed to describe the phenotypic variation within a large family with ADH, especially kidney and cerebral basal ganglia calcifications. Methods: Fifteen related subjects carrying the CASR mutation T151M participated in a cross-sectional study of calcium homeostasis, renal ultrasonography, cerebral CT, bone mineral density, and health-related quality of life (HRQoL). Results: Eight subjects had received vitamin D treatment (mean duration 15.3 years; range 11–20 years). Urinary calcium excretion was elevated in 5/8 vitamin-D-treated and in 3/7 untreated subjects. Serum magnesium, calcium and parathyroid hormone remained at the lower reference limit or below. Renal calcifications were found in 12 of 14 (86%) and basal ganglia calcifications in 5 of 11 (46%) subjects, independently of vitamin D therapy. The glomerular filtration rate was moderately reduced in 3 subjects. Mean bone mineral density and bone markers were normal. HRQoL was impaired in the vitamin-D-treated group despite correction of the hypocalcaemia. Conclusions: The impact of the CASR mutation on calcium homeostasis varied greatly. Kidney and basal ganglia calcifications are common in ADH independently of vitamin D treatment, which, however, increases urinary calcium excretion and may promote urolithiasis.
Ethical Principles for the Management of Infants with Disorders of Sex Development
Authors: Gillam Lynn H. , Hewitt Jacqueline K. , Warne Garry L.
Published: November 2010

The Fifth World Congress on Family Law and Children’s Rights (Halifax, August 2009) adopted a resolution endorsing a new set of ethical guidelines for the management of infants and children with disorders of sex development (DSD) [www.lawrights.asn.au/index.php?option=com_content&view=article&id=76&Itemid=109]. The ethical principles developed by our group were the basis for the Halifax Resolution. In this paper, we outline these principles and explain their basis. The principles are intended as the ethical foundation for treatment decisions for DSD, especially decisions about type and timing of genital surgery for infants and young children. These principles were formulated by an analytic review of clinician reasoning in particular cases, in relation to established principles of bioethics, in a process consistent with the Rawlsian concept of reflective equilibrium as the method for building ethical theory. The principles we propose are: (1) minimising physical risk to child; (2) minimising psychosocial risk to child; (3) preserving potential for fertility; (4) preserving or promoting capacity to have satisfying sexual relations; (5) leaving options open for the future, and (6) respecting the parents’ wishes and beliefs.
Associations of Progesterone Receptor Polymorphisms with Age at Menarche and Menstrual Cycle Length
Authors: Taylor K.C. , Small C.M. , Epstein M.P. , Sherman S.L. , Tang W. , Wilson M.M. , Bouzyk M. , Marcus M.
Published: November 2010

Background: Age at menarche and menstrual cycle characteristics are indicators of endocrine function and may be risk factors for diseases such as reproductive cancers. The progesterone receptor gene (PGR) has been identified as a candidate gene for age at menarche and menstrual function. Methods: Women office workers ages 19–41 self-reported age at menarche and participated in a prospective study of menstrual function and fertility. First-morning urine was used as the DNA source. 444 women were genotyped for a functional variant in PGR, rs1042838 (Val660Leu), and 264 women were also genotyped for 29 other SNPs across the extended gene region. Results: Genetic variation across PGR was associated with age at menarche using a global score statistic (p = 0.03 among non-Hispanic whites). Women carrying two copies of the Val660Leu variant experienced menarche 1 year later than women carrying one or no copies of the variant (13.6 ± 0.5 vs. 12.6 ± 0.1; p = 0.03). The Val660Leu variant was also associated with decreased odds of short menstrual cycles (17–24 days) (OR, 95% CI: 0.54 [0.36, 0.80]; p = 0.002). Conclusion: Genetic variation in PGR was associated with age at menarche and menstrual cycle length in this population. Further investigation of these associations in a replication dataset is warranted.
Obesity Affects the Liver – The Link between Adipocytes and Hepatocytes
Authors: Wree Alexander , Kahraman Alisan , Gerken Guido , Canbay Ali
Published: November 2010

The incidence of obesity has dramatically increased in recent years. Consequently, obesity and associated disorders such as nonalcoholic fatty liver disease (NAFLD) constitute a serious threat. Therefore, the contribution of visceral adipose tissue to metabolic homeostasis has become a focus of interest. Visceral adipose tissue secretes free fatty acids (FFAs) and hormones, known as adipokines, and thus seems to play a major role in the development of NAFLD. Apoptotic cell death is a prominent feature in nonalcoholic steatohepatitis (NASH). Indeed, toxic FFAs can activate the intrinsic apoptosis pathway in hepatocytes via c-Jun N-terminal kinase (JNK). JNK activates the proapoptotic protein Bim, resulting in Bax activation and enhanced apoptosis, termed ‘lipoapoptosis’. Reduced adiponectin levels may establish a proinflammatory milieu, thus increasing vulnerability to lipotoxicity, which promotes progression from simple steatosis to NASH and even advanced hepatic fibrosis. Moreover, obesity seems to be a risk factor for hepatocellular carcinoma, the most frequent liver cancer subtype. Even in acute liver failure, a high body mass index is associated with poor outcome, and recent data suggest a major role of obesity in the progression of chronic hepatitis C and B. This review summarizes current knowledge – highlighting the inflammatory and cytokine view – of the intimate relationship between adipose and liver tissue.
Natural History of Idiopathic Advanced Bone Age Diagnosed in Childhood: Pattern of Growth and Puberty
Authors: Lazar Liora , Lebenthal Yael , Shalitin Shlomit , Phillip Moshe
Published: November 2010

Background: Significant idiopathic bone age (BA) advancement is defined as BA >2 SD above the mean chronological age (CA) with no underlying etiology. BA advancement due to endocrinopathies is associated with early puberty and compromised adult height (AHt), necessitating treatment. The natural history of idiopathic BA advancement is not well-established. Aim: To determine the pattern of growth and puberty, and validity of AHt prediction in idiopathic BA advancement. Methods: Fifty-five prepubertal patients (20 boys aged 6.7 ± 2.2 years, 35 girls aged 6.4 ± 2.0 years) evaluated between 1985 and 2008 were found to have idiopathic BA advancement. Assessed during follow-up were: BA, height (Ht), weight (Wt), pubertal course and predicted AHt (PAHt). Attained AHt was compared to PAHt and to midparental Ht (MPHt). Results: Throughout follow-up, BA-SDS (SD score) significantly declined (p < 0.001), Ht-SDS significantly decreased (p = 0.006) and Wt-SDS did not change. Pubertal onset, duration and growth were within the normal range. Attained AHts did not differ significantly from MPHts (boys: 172 ± 6.7 vs. 171 ± 6.1 cm; girls: 160.5 ± 6.5 vs. 159.0 ± 6.8 cm). PAHts using the ‘accelerated’ tables of Bayley and Pinneau were accurate. Conclusion: Idiopathic BA advancement differs from BA advancement with underlying endocrinopathy in evolution of BA progression (decline in BA-SDS), growth pattern, validity of AHt prediction and uncompromised AHt. This indicates that it requires minimal clinical monitoring and usually does not mandate treatment.
Diagnostic and Prognostic Validity of Golgi Protein 73 in Hepatocellular Carcinoma
Authors: Özkan Hasan , Erdal Harun , Tutkak Hüseyin , Karaeren Zihni , Yakut Mustafa , Yüksel Osman , Köklü Seyfettin
Published: November 2010

We regret to inform you that the criticism raised by the Editorial Board is correct concerning the similarity between some parts of the texts present in our article published in Digestion [2011;83:83–88], and the papers in the Journal of Hepatology [2005;43:1007–1012] and in Hepatology [2009;49:1421–1423], although the research data are completely independent. We apologize for this unfortunate error, which was established during the writing process of the manuscript by the author Harun Erdal. Although the final version of the submitted paper had been examined by all authors, they failed to recognize the ‘transferred parts’ of the papers in the Journal of Hepatology [2005;43:1007–1012] and in Hepatology [2009;49:1421–1423]. Thus, for the sake of scientific clarity and based on the above-mentioned facts, we prefer to retract our paper Diagnostic and Prognostic Validity of Golgi Protein 73 in Hepatocellular Carcinoma. Digestion 2011;83:83–88 (DOI:10.1159/000320379). Authors, Hasan Özkan Harun Erdal Hüseyin Tutkak Zihni Karaeren Mustafa Yakut Osman Yüksel Seyfettin Köklü
Serological and Clinical Follow-Up of Relatives of Celiac Disease Patients from Southern Brazil
Authors: Nass Flávia Raphaela , Kotze Lorete Maria da Silva , Nisihara Renato Mitsunori , de Messias-Reason Iara José , Ramos da Rosa Utiyama Shirley
Published: November 2010

Background/Aims: In this study, a clinical and serological follow-up of 8–10 years was performed in relatives of celiac disease (CD) patients from southern Brazil. The occurrence of new CD cases in the families and the use of two different IgA-tTG enzyme-linked immunosorbent assay (ELISA) kits were also evaluated. Methods: Serum samples of 233 relatives, 186 recruited between 1997 and 2000 (phase I) and 138 between 2006 and 2007 (phase II: 91 of the follow-up group and 47 newly tested), were analyzed. As a comparison group, 100 unrelated healthy individuals were evaluated. IgA-EmA was tested by indirect immunofluorescence and IgA-tTG by ELISA. Results: A significant increase in IgA-EmA/IgA-tTG was detected in relatives of patients with CD when compared to controls (p ≤ 0.001). The positivity of antibodies was higher in females (2.4:1 in phase II; p = 0.039), and its high frequency amongst siblings (∼18.81%) highlights the risk of CD in these individuals. The distribution of antibodies by age suggested that CD can occur at any age in relatives, calling attention to the newly tested relatives >60 years of age (p = 0.0657). A better performance of ELISA kits with human tTG was observed. The confirmation of 13 biopsy-proven new CD cases (5.6%; 13/233) at present points out the predisposition to CD in these individuals and the high specificity of concurrently positive antibodies in relatives, especially when both are present in high titers. Conclusion: These results emphasize the familial risk to develop CD and the value of serological screening as an instrument for identifying this disease.
Pediatric Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)
Authors: Ko Melissa W. , Liu Grant T.
Published: November 2010

Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is a condition of elevated intracranial pressure in the absence of clinical, laboratory or radiological evidence of an intracranial space occupying lesion that can occur in the pediatric population. While IIH is more commonly recognized as a disorder of adults, it affects children of all ages and can have distinctive characteristics when presenting in the prepubertal age group. This review discusses the demographics, clinical presentation, diagnosis, neuroimaging, and management of pediatric IIH. Common etiologies of IIH in children, with particular focus on endocrine abnormalities, are highlighted.
The ‘Clean Wehrmacht’ in the German-occupied Netherlands, 1940-5
Authors: Foray Jennifer L.
Published: November 2010

Typically, discussions of a purportedly ‘clean Wehrmacht’ — and its counterpart, the ‘barbarization of warfare’ concept — have centered upon developments in wartime Poland and the western reaches of the Soviet Union. However, the situation in Western Europe merits further analysis, if only because the notion of an apolitical, upright Wehrmacht existed in the Netherlands, too. Drawing upon situation reports generated by the Netherlands’ military occupiers, this article examines both the Wehrmacht’s attempts to avoid the ideological excesses of its civilian counterparts and the progressive deterioration of the army’s situation in this western corner of the nazi New Order. Ultimately, mounting physical privations, growing popular hostility, and the nazi regime’s demand for co-operation in enforcing anti-Jewish measures would undo the military’s attempt to remain out of the fray of politics. As in Eastern Europe, the idea of a ‘clean Wehrmacht’ in the Netherlands would prove more myth than reality.