bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial Ischemia in Women: Lessons From the NHLBI WISE Study
Authors: Gulati Martha , Shaw Leslee J. , Bairey Merz C. Noel
Published: March 2012

Cardiovascular disease (CVD) remains the leading cause of death for women. For almost 3 decades, more women than men have died from CVD, with the most recent annual statistics on mortality reporting that CVD accounted for 421 918 deaths among women in the United States. Although there have been significant declines in coronary heart disease (CHD) mortality for females, these reductions lag behind those seen in men. In addition, where there has been a decrease in mortality from CHD across all age groups over time in men, in the youngest women (age <55 years) there has been a notable increase in mortality from CHD. There are differences in the prevalence, symptoms, and pathophysiology of myocardial ischemia that occurs in women compared with men. In this paper, we review the pathophysiology and mechanisms of ischemic heart disease (IHD) in women, particularly focusing on what we have learned from the WISE study. We examine the sex‐specific issues related to myocardial ischemia in women in terms of prevalence and prognosis, traditional and novel risk factors, diagnostic testing, as well as therapeutic management strategies for IHD. © 2012 Wiley Periodicals, Inc.

This work was supported by contracts from the National Heart, Lung, and Blood Institute, nos. N01‐HV‐68161, N01‐HV‐68162, N01‐HV‐68163, N01‐HV‐68164, and R01 HL090957‐01A1; grants U0164829, U01 HL649141, U01 HL649241, T32HL69751, and R03 AG032631‐01 from the National Institute on Aging; a GCRC grant MO1‐RR00425 from the National Center for Research Resources; and grants from the Gustavus and Louise Pfeiffer Research Foundation, Danville, New Jersey; the Women's Guild of Cedars‐Sinai Medical Center, Los Angeles, California; the Edythe L. Broad Women's Heart Research Fellowship, Cedars‐Sinai Medical Center, Los Angeles, California; and the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars‐Sinai Medical Center, Los Angeles. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Cardiovascular Disease: The Female Heart Is Vulnerable
Authors: Wenger Nanette K.
Published: March 2012

February was Heart Month. Clinical Cardiology has embraced the opportunity to share with clinicians and scientists the major adverse impact of cardiovascular disease in women, identifying actionable items derived from recent research studies and highlighting gaps in our knowledge that require investigation. © 2012 Wiley Periodicals, Inc.

The invited expert clinician/scientists in this issue of Clinical Cardiology, Drs. Noel Bairey Merz, Pamela Ouyang, Leslee Shaw, and Nanette Wenger, are members of the Society for Women's Health Research, Interdisciplinary Studies In Sex‐differences (ISIS) Network on Cardiovascular Disease.

The author has no funding, financial relationships, or conflicts of interest to disclose.
Bulbispermine: A Crinine‐Type Amaryllidaceae Alkaloid Exhibiting Cytostatic Activity toward Apoptosis‐Resistant Glioma Cells
Authors: Luchetti Giovanni , Johnston Robert , Mathieu Véronique , Lefranc Florence , Hayden Kathryn , Andolfi Anna , Lamoral‐Theys Delphine , Reisenauer Mary R. , Champion Cody , Pelly Stephen C. , van Otterlo Willem A. L. , Magedov Igor V. , Kiss Robert , Evidente Antonio , Rogelj Snezna , Kornienko Alexander
Published: March 2012

The Amaryllidaceae alkaloid bulbispermine was derivatized to produce a small group of synthetic analogues. These, together with bulbispermine’s natural crinine‐type congeners, were evaluated in vitro against a panel of cancer cell lines with various levels of resistance to pro‐apoptotic stimuli. Bulbispermine, haemanthamine, and haemanthidine showed the most potent antiproliferative activities as determined by the MTT colorimetric assay. Among the synthetic bulbispermine analogues, only the C1,C2‐dicarbamate derivative exhibited notable growth inhibitory properties. All active compounds were found not to discriminate between the cancer cell lines based on the apoptosis sensitivity criterion; they displayed similar potencies in both cell types, indicating that the induction of apoptosis is not the primary mechanism responsible for antiproliferative activity in this series of compounds. It was also found that bulbispermine inhibits the proliferation of glioblastoma cells through cytostatic effects, possibly arising from rigidification of the actin cytoskeleton. These findings lead us to argue that crinine‐type alkaloids are potentially useful drug leads for the treatment of apoptosis‐resistant cancers and glioblastoma in particular.
Evidence for a Specific Impairment of Serial Order Short‐term Memory in Dyslexic Children
Authors: Perez Trecy Martinez , Majerus Steve , Mahot Aline , Poncelet Martine
Published: March 2012

In order to better understand the nature of verbal short‐term memory (STM) deficits in dyslexic children, the present study used the distinction between item and serial order retention capacities in STM tasks. According to recent STM models, storage of verbal item information depends very directly upon the richness of underlying phonological and semantic representations. On the other hand, storage of serial order information appears to reflect a language‐independent system. Hence, if there is a fundamental STM deficit in dyslexia that is not to be explained only by the poor phonological processing abilities that characterize dyslexia, then difficulties in serial order STM should also be observed in dyslexic children. We administered tasks maximizing either serial order or item retention capacities to dyslexic children and reading age (RA) and chronological age (CA) matched controls. Dyslexic children performed significantly poorer than the CA controls on the item STM measure. Furthermore, the dyslexic group obtained inferior performance than both CA and RA control groups on the serial order STM measure. These findings highlight a severe impairment of STM for serial order information in dyslexia that cannot be reduced to a phonological processing impairment. Implications of serial order retention deficits for reading acquisition and dyslexia are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Lipase‐catalyzed transesterification to remove saturated MAG from biodiesel
Authors: Padhi Santosh Kumar , Haas Michael , Bornscheuer Uwe T.
Published: March 2012

Saturated MAG (SMG) are known to be present in FAME intended to be used as biodiesel. These SMG can strongly affect the properties of biofuels such as the cloud point (CP), and they have been implicated in engine failure due to filter plugging. It is shown here that lipase G from Penicillium camemberti can be efficiently used for the transesterification of SMG to fatty acid methyl ester and glycerol even in the presence of the bulk biodiesel. Thus, in samples of commercial biodiesel to which glycerol monostearate (GMS) and glycerol monopalmitate (GMP) had been added, their levels were enzymatically reduced from 2% (w/v) to 0.22% (w/v) for GMP and 0.14% (w/v) for GMS as confirmed by GC‐MS analysis.

Practical applications: SMG present in biodiesel can have a pronounced negative effect on the CP, and/or filterability and in‐field performance of the fuel. The lipase‐catalyzed transesterification shown in this paper enables a significant reduction in the amount of SMG, leading to superior biodiesel quality.
Direct Amination of Nitro(pentafluorosulfanyl)benzenes through Vicarious Nucleophilic Substitution of Hydrogen
Authors: Pastýříková Tereza , Iakobson George , Vida Norbert , Pohl Radek , Beier Petr
Published: March 2012

1‐Nitro‐4‐(pentafluorosulfanyl)benzene underwent direct amination with 1,1,1‐trimethylhydrazinium iodide in the presence of tBuOK in DMSO to give 2‐nitro‐5‐(pentafluorosulfanyl)aniline in good yield. 1‐Nitro‐3‐(pentafluorosulfanyl)benzene, under similar conditions, gave 2‐nitro‐4‐(pentafluorosulfanyl)aniline, also in good yield. Reduction of either product with hydrogen in the presence of Raney nickel provided 4‐(pentafluorosulfanyl)benzene‐1,2‐diamine, which served as a precursor for the efficient synthesis of SF5‐containing benzimidazoles, quinoxalines, and benzotriazoles.
Impairments in aromatase expression, reproductive behavior, and sperm quality of male fish exposed to 17β-estradiol
Authors: Guyón Noelia F. , Roggio María A. , Amé María V. , Hued Andrea C. , Valdés María E. , Giojalas Laura C. , Wunderlin Daniel A. , Bistoni María A.
Published: March 2012

Growing evidence shows that environmental estrogen can reach levels that are high enough to exert adverse reproductive effects on wild fish populations. The authors report different parameters of male reproductive behavior, brain, and gonadal aromatase expression, as well as sperm quality in an internally fertilizing fish species (Jenynsia multidentata, Jenyns) exposed to environmentally relevant concentrations of 17β-estradiol (E2). Adult males were exposed to 0, 50, 100, and 250 ng/L E2 over 28 d. The authors' findings demonstrate that E2 exposure resulted in a very clear increase in brain aromatase transcript abundance at all assayed concentrations compared with control; however, no effects on gonadal aromatase expression were observed. Behavioral measures revealed increased sexual activity at 50 ng/L but not 100 or 250 ng/L E2. In contrast to the molecular and behavioral responses, the condition factor, gonadosomatic index, and sperm quality were unaltered by E2 exposure. The results from the present work suggest that E2 affects some aspects of the reproductive biology of J. multidentata. These modifications in the reproductive biology caused by exposure to E2 could potentially lead to long-term effects at population levels that may not always be immediately evident. To the best of the authors' knowledge, this is the first report on the combined effect of E2 on aromatase expression, sexual behavior, and sperm parameters in fish. Environ. Toxicol. Chem. 2012; 31: 935–940. © 2012 SETAC
TAT-apoptosis repressor with caspase recruitment domain protein transduction rescues mice from fulminant liver failure
Authors: An Junfeng , Harms Christoph , Lättig-Tünnemann Gisela , Sellge Gernot , Mandić Ana D. , Malato Yann , Heuser Arnd , Endres Matthias , Trautwein Christian , Donath Stefan
Published: March 2012

Acute liver failure (ALF) is associated with massive hepatocyte cell death and high mortality rates. Therapeutic approaches targeting hepatocyte injury in ALF are hampered by the activation of distinct stimulus-dependent pathways, mechanism of cell death, and a limited therapeutic window. The apoptosis repressor with caspase recruitment domain (ARC) is a recently discovered death repressor that inhibits both death receptor and mitochondrial apoptotic signaling. Here, we investigated the

in vivo

effects of ARC fused with the transduction domain of human immunodeficiency virus 1 (HIV-1) (TAT-ARC) on Fas- and tumor necrosis factor (TNF)-mediated murine models of fulminant liver failure. Treatment with TAT-ARC protein completely abrogated otherwise lethal liver failure induced by Fas-agonistic antibody (Jo2), concanavalin A (ConA), or D-galactosamine/lipopolysaccharide (GalN/LPS) administration. Importantly, survival of mice was even preserved when TAT-ARC therapy was initiated in a delayed manner after stimulation with Jo2, ConA, or GalN/LPS. ARC blocked hepatocyte apoptosis by directly interacting with members of the death-inducing signaling complex. TNF-mediated liver damage was inhibited by two independent mechanisms: inhibition of jun kinase (JNK)-mediated TNF-α expression and prevention of hepatocyte apoptosis by inhibition of both death receptor and mitochondrial death signaling. We identified JNK as a novel target of ARC. ARC's caspase recruitment domain (CARD) directly interacts with JNK1 and JNK2, which correlates with decreased JNK activation and JNK-dependent TNF-α production.

Conclusion

: This work suggests that ARC confers hepatoprotection upstream and at the hepatocyte level. The efficacy of TAT-ARC protein transduction in multiple murine models of ALF demonstrates its therapeutic potential for reversing liver failure. (HEPATOLOGY 2012)
Hepatocyte senescence in vivo following preconditioning for liver repopulation
Authors: Serra Maria Paola , Marongiu Fabio , Sini Marcella , Laconi Ezio
Published: March 2012

In the retrorsine (RS)-based model of massive liver repopulation, preexposure to this naturally occurring alkaloid is sufficient to prime normal host parenchymal cells to be slowly replaced by transplanted normal hepatocytes. The basis for this striking effect is yet to be fully elucidated. In the present studies the possible involvement of cell senescence was investigated. Fischer 344 rats were treated according to the RS-based protocol for hepatocyte transplantation, i.e., two doses of RS, 2 weeks apart, and were killed at 4 or 8 weeks after treatment. Control groups were given saline. Expression of senescence-associated beta-galactosidase was greatly induced in hepatocytes exposed to RS. In addition, several other changes that have been related to cell senescence were observed: these included markers of persistent activation of a DNA damage response, an increased expression of mammalian target of rapamycin, and positive regulators of the cell cycle, together with the induction of p21 and p27 cyclin-dependent kinase inhibitors. Furthermore, RS treatment increased levels of interleukin-6 in the liver, consistent with the activation of a senescence-associated secretory phenotype.

Conclusion:

These findings indicate that RS induces hepatocyte senescence

in vivo

. We propose that cell senescence and the associated secretory phenotype can contribute to the selective growth of transplanted hepatocytes in this system. (HEPATOLOGY 2012)
Histone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer
Authors: Jung Kwang Hwa , Noh Ji Heon , Kim Jeong Kyu , Eun Jung Woo , Bae Hyun Jin , Chang Young Gyoon , Kim Min Gyu , Park Won Sang , Lee Jung Young , Lee Sang-Yeop , Chu In-Sun , Nam Suk Woo
Published: March 2012

Ubiquitin-binding histone deacetylase 6 (HDAC6) is uniquely endowed with tubulin deacetylase activity and plays an important role in the clearance of misfolded protein by autophagy. In cancer, HDAC6 has become a target for drug development due to its major contribution to oncogenic cell transformation. In the present study we show that HDAC6 expression was down-regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, and that low expression of HDAC6 was significantly associated with poor prognosis of HCC patients in 5-year overall, disease-free, and recurrence-free survival. Notably, we observed that ectopic overexpression of HDAC6 suppressed tumor cell growth and proliferation in various liver cancer cells, and elicited increased LC3B-II conversion and autophagic vacuole formation without causing apoptotic cell death or cell cycle inhibition. In addition, the sustained overexpression of HDAC6 reduced the

in vivo

tumor growth rate in a mouse xenograft model. It was also found that HDAC6 mediated autophagic cell death by way of Beclin 1 and activation of the LC3-II pathway in liver cancer cells, and that HDAC6 overexpression activated c-Jun NH2-terminal kinase (JNK) and increased the phosphorylation of c-Jun. In contrast, the induction of Beclin 1 expression was blocked by SP600125 (a specific inhibitor of JNK) or by small interfering RNA directed against HDAC6.

Conclusion:

Our findings suggest that loss of HDAC6 expression in human HCCs and tumor suppression by HDAC6 occur by way of activation of caspase-independent autophagic cell death through the JNK/Beclin 1 pathway in liver cancer and, thus, that a novel tumor suppressor function mechanism involving HDAC6 may be amenable to nonepigenetic regulation. (HEPATOLOGY 2012)
Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine
Authors: Corazza Ornella , Schifano Fabrizio , Simonato Pierluigi , Fergus Suzanne , Assi Sulaf , Stair Jacqueline , Corkery John , Trincas Giuseppina , Deluca Paolo , Davey Zoe , Blaszko Ursula , Demetrovics Zsolt , Moskalewicz Jacek , Enea Aurora , di Melchiorre Giuditta , Mervo Barbara , di Furia Lucia , Farre Magi , Flesland Liv , Pasinetti Manuela , Pezzolesi Cinzia , Pisarska Agnieszka , Shapiro Harry , Siemann Holger , Skutle Arvid , Enea Aurora , di Melchiorre Giuditta , Sferrazza Elias , Torrens Marta , van der Kreeft Peer , Zummo Daniela , Scherbaum Norbert
Published: March 2012

On the basis of the material available both in the scientific literature and on the web, this paper aims to provide a pharmacological, chemical and behavioural overview of the novel compound methoxetamine. This is a dissociative drug related to ketamine, with a much longer duration of action and intensity of effects. A critical discussion of the availability of information on the web of methoxetamine as a new recreational trend is here provided. Those methodological limitations, which are intrinsically associated with the analysis of online, non‐peer reviewed, material, are here discussed as well. It is concluded that the online availability of information on novel psychoactive drugs, such as methoxethanine, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast‐growing phenomenon. Copyright © 2012 John Wiley & Sons, Ltd.
Regulation of the human endogenous retroviral Syncytin‐1 and cell–cell fusion by the nuclear hormone receptors PPARγ/RXRα in placentogenesis
Authors: Ruebner Matthias , Langbein Manuela , Strissel Pamela L. , Henke Christine , Schmidt Doreen , Goecke Tamme W. , Faschingbauer Florian , Schild Ralf L. , Beckmann Matthias W. , Strick Reiner
Published: March 2012

Cytotrophoblast (CT) cell fusion into a syncytiotrophoblast is obligatory for placentation and mediated by the human endogenous retrovirus (HERV)‐W envelope gene Syncytin‐1. Abnormal placentation is associated with preeclampsia (PE), HELLP and intrauterine growth restriction (IUGR). In placentogenesis, the MAP‐kinase p38α regulates PPARγ/RXRα signaling and target genes, like leptin, resistin, ABCG2, and hCG. The aim of this study was to analyze PPARγ/RXRα signaling and target gene regulation using primary CT cultures, the trophoblastic cell line BeWo and placental tissues from patients with normal and abnormal placentation. CT from four different human control placentae and BeWo cells demonstrated that Syncytin‐1, other signaling members and CT cell fusions were regulated with PPARγ/RXRα activators troglitazone and 9‐cis retinoic acid, via protein kinase A and p38α inhibition. Significant discordant regulations between CTs and BeWo were found. Two PPARγ/RXRα‐response‐elements from upstream regulatory elements and the 5′LTR of HERV‐W were confirmed with DNA‐protein binding assays using nuclear extracts and recombinant PPARγ/RXRα proteins. These promoter elements were validated with luciferase assays in the presence of PPARγ/RXRα modulators. Furthermore, troglitazone or 9‐cis retinoic acid treatment of siRNA‐PPARγ and siRNA‐RXRα transfected BeWo cells proved the requirement of these proteins for Syncytin‐1 regulation. Thirty primary abnormal placentae from PE, HELLP and IUGR patients compared to 10 controls showed significant deregulation of leptin RNA and protein, p38α, phospho‐p38α, PPARγ, ABCG2, INSL4 and Syncytin‐1. Our study characterized PPARγ/RXRα signaling in human CT and cell fusions identifying Syncytin‐1 as a new target gene. Based on these results, a disturbed PPARγ/RXRα pathway could contribute to pathological human pregnancies. J. Cell. Biochem. 113: 2383–2396, 2012. © 2012 Wiley Periodicals, Inc.
A novel Phex mutation in a new mouse model of hypophosphatemic rickets
Authors: Owen Celeste , Chen Frieda , Flenniken Ann M. , Osborne Lucy R. , Ichikawa Shoji , Adamson S. Lee , Rossant Janet , Aubin Jane E.
Published: March 2012

X‐linked hypophosphatemic rickets (XLH) is a dominantly inherited disease characterized by renal phosphate wasting, aberrant vitamin D metabolism, and defective bone mineralization. It is known that XLH in humans and in certain mouse models is caused by inactivating mutations in PHEX/Phex (phosphate‐regulating gene with homologies to endopeptidases on the X chromosome). By a genome‐wide N‐ethyl‐N‐nitrosourea (ENU)‐induced mutagenesis screen in mice, we identified a dominant mouse mutation that exhibits the classic clinical manifestations of XLH, including growth retardation, skeletal abnormalities (rickets/osteomalacia), hypophosphatemia, and increased serum alkaline phosphatase (ALP) levels. Mapping and sequencing revealed that these mice carry a point mutation in exon 14 of the Phex gene that introduces a stop codon at amino acid 496 of the coding sequence (PhexJrt also published as PhexK496X [Ichikawa et al., 2012]). Fgf23 mRNA expression as well as that of osteocalcin, bone sialoprotein, and matrix extracellular phosphoglycoprotein was upregulated in male mutant long bone, but that of sclerostin was unaffected. Although Phex mRNA is expressed in bone from mutant hemizygous male mice (PhexJrt/Y mice), no Phex protein was detected in immunoblots of femoral bone protein. Stromal cultures from mutant bone marrow were indistinguishable from those of wild‐type mice with respect to differentiation and mineralization. The ability of PhexJrt/Y osteoblasts to mineralize and the altered expression levels of matrix proteins compared with the well‐studied Hyp mice makes it a unique model with which to further explore the clinical manifestations of XLH and its link to FGF23 as well as to evaluate potential new therapeutic strategies. J. Cell. Biochem. 113: 2432–2441, 2012. © 2012 Wiley Periodicals, Inc.
The emerging role of Arf/Arl small GTPases in cilia and ciliopathies
Authors: Li Yujie , Ling Kun , Hu Jinghua
Published: March 2012

Once overlooked as an evolutionary vestige, the primary cilium has recently been the focus of intensive studies. Mounting data show that this organelle is a hub for various signaling pathways during vertebrate embryonic development and pattern formation. However, how cilia form and how cilia execute the sensory function still remain poorly understood. Cilia dysfunction is correlated with a wide spectrum of human diseases, now termed ciliopathies. Various small GTPases, including the members in Arf/Arl, Rab, and Ran subfamilies, have been implicated in cilia formation and/or function. Here we review and discuss the role of one particular group of small GTPase, Arf/Arl, in the context of cilia and ciliopathy. J. Cell. Biochem. 113: 2201–2207, 2012. © 2012 Wiley Periodicals, Inc.
Simulated infrared spectra of triflic acid during proton dissociation
Authors: Laflamme Patrick , Beaudoin Alexandre , Chapaton Thomas , Spino Claude , Soldera Armand
Published: March 2012

Vibrational analysis of triflic acid (TfOH) at different water uptakes was conducted. This molecule mimics the sulfonate end of the Nafion® side‐chain. As the proton leaves the sulfonic acid group, structural changes within the Nafion® side‐chain take place. They are revealed by signal shifts in the infrared spectrum. Molecular modeling is used to follow structural modifications that occur during proton dissociation. To confirm the accuracy of the proposed structures, infrared spectra were computed via quantum chemical modeling based on density functional theory. The requirement to use additional diffuse functions in the basis set is discussed. Comparison between simulated infrared spectra of 1 and 2 acid molecules with different water contents and experimental data was performed. An accurate description of infrared spectra for systems containing 2 TfOH was obtained. © 2012 Wiley Periodicals, Inc.
A stepwise retro‐imino‐ene as a key step in the mechanism of allene formation via the Crabbé acetylene homologation
Authors: González Marta , Rodríguez Roi Álvarez , Cid Maria Magdalena , López Carlos Silva
Published: March 2012

The mechanism of the acetylene homologation procedure accidentally discovered and further developed by Crabbé and coworkers is unknown. Kinetic isotope effect (KIE) experiments, however, suggest that an intramolecular hydrogen shift is the key step of the transformation. In this work, we present a computational study of this mechanism. We found that the reaction proceeds via an unexpected stepwise retro‐imino‐ene rearrangement. This mechanism justifies the role of Cu(I) as a reaction catalyst and is also compatible with the KIE experiments reported. © 2012 Wiley Periodicals, Inc.
The expression and role of non‐canonical (PKC) signaling in nucleus pulposus cell metabolism
Authors: Arai Fumiyuki , Hiyama Akihiko , Sakai Daisuke , Yokoyama Katsuya , Mochida Joji
Published: March 2012

Canonical Wnt/β‐catenin (hereafter Wnt) signaling regulates the proliferation and differentiation of various cell types. However, the role of non‐canonical signaling including protein kinase C (PKC) signaling has not been investigated in intervertebral disc (IVD) cells. The aim of this study was to elucidate whether the activation of PKC signaling act to modulate Wnt signaling in IVD cells. We performed several reporter assays, real‐time reverse transcription polymerase chain reaction (RT‐PCR), immunohistochemical and immunofluorescence analyses, and western blot analyses using rat nucleus pulposus (NP) cells. We also examined the cell proliferation and cell cycle distribution under phorbol 12‐myristate 13‐acetate (PMA) stimulation, a known activator of PKC signaling. We found that NP cells exhibited decreased β‐catenin mRNA and protein levels upon stimulation with PMA. PMA treatment promoted proliferation and cell cycle progression in a time‐ and dose‐dependent manner. In addition, activation of the PKC signaling also regulated the expression of aggrecan. Finally, activation by PMA induced the expression of several PKC isoforms in NP cells. It is concluded that activation of PKC signaling might lead to an increase in matrix synthesis and cell proliferation, thereby inhibiting IVD degeneration. Crosstalk in these signaling pathways plays an important role in the regulation of IVD homeostasis. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1478–1485, 2012
Energetic boundary element method analysis of wave propagation in 2D multilayered media
Authors: Aimi A. , Gazzola S. , Guardasoni C.
Published: March 2012

The analysis of scalar wave propagation in 2D zonewise homogeneous media with vanishing initial and mixed boundary conditions is carried out. The problem is formulated in terms of time‐dependent boundary integral equations, and then it is set in a weak form, based on a natural energy identity satisfied by the differential problem solution. Several numerical results have been obtained by means of the related energetic Galerkin boundary element method showing accuracy and stability of the method. Copyright © 2012 John Wiley & Sons, Ltd.
Mixed integer least squares optimization for flight and maintenance planning of mission aircraft
Authors: Kozanidis George , Gavranis Andreas , Kostarelou Eftychia
Published: March 2012

We address the problem of generating a joint flight and maintenance plan for a unit of mission aircraft. The objective is to establish a balanced allocation of the flight load and the maintenance capacity to the individual aircraft of the unit, so that its long‐term availability is kept at a high and steady level. We propose a mixed integer nonlinear model to formulate the problem, the objective function of which minimizes a least squares index expressing the total deviation of the individual aircraft flight and maintenance times from their corresponding target values. Using the model's special structure and properties, we develop an exact search algorithm for its solution. We analyze the computational complexity of this algorithm, and we present computational results comparing its performance against that of a commercial optimization package. Besides demonstrating the superiority of the proposed algorithm, these results reveal that the total computational effort required for the solution of the problem depends mainly on two crucial parameters: the size of the unit (i.e., the number of aircraft that comprise it) and the space capacity of the maintenance station. © 2012 Wiley Periodicals, Inc. Naval Research Logistics, 2012
Results of AIEOP LNH‐97 protocol for the treatment of anaplastic large cell lymphoma of childhood
Authors: Pillon Marta , Gregucci Fabiana , Lombardi Alessandra , Santoro Nicola , Piglione Matilde , Sala Alessandra , D'Amore Emanuele S.G. , De Santis Raffaela , Casale Fiorina , Zecca Marco , Mussolin Lara , Rosolen Angelo ,   On behalf of the NHL‐Committee of the Italian Association of Pediatric Hematology and Oncology (AIEOP)
Published: March 2012

Background

Anaplastic large cell lymphoma (ALCL) represents approximately 15% of all pediatric non‐Hodgkin lymphomas (NHL). It has distinct clinical features, including frequent involvement of extranodal sites and rare localization to the central nervous system (CNS). Despite varying treatment approaches the outcome of patients with ALCL has not significantly improved during the last two decades.

Procedure

From October 1997 to beginning of 2000, newly diagnosed ALCL patients were enrolled into AIEOP LNH‐97 protocol for ALCL. Thereafter and until 2007, only CNS positive patients were included. AIEOP LNH‐97 was based on the BFM‐95 schema for ALCL and included six high‐dose chemotherapy courses. CNS prophylaxis was obtained with one intrathecal injection of chemotherapy in each course, whereas treatment of CNS involvement included three intrathecal injections without irradiation.

Results

Thirty‐two patients were eligible for the study. Lymph‐node disease was the most frequent localization (69% of the cases), followed by mediastinal (25%), CNS (22%), bone marrow (16%), and skin (13%) involvement. Probabilities of overall survival (OS) and of event‐free survival (EFS) at 5 years for the whole population were 87% (SE 6%) and 68% (SE 8%), respectively.

Conclusions

This study confirmed that short pulse chemotherapy is an efficacious treatment option for first line therapy of pediatric ALCL, and that dose intensity may have some relevance for outcome, but not in all of the patients. Refinement and optimization of therapy strategies for ALCL may originate from a combination of clinical and biological prospective studies, as those in the pipeline of current international collaboration. Pediatr Blood Cancer 2012; 59: 828–833. © 2012 Wiley Periodicals, Inc.
Interaction of l‐leucyl‐l‐leucyl‐l‐leucine thin film with water and organic vapors: receptor properties and related morphology
Authors: Ziganshin Marat A. , Efimova Irina G. , Gorbatchuk Valery V. , Ziganshina Sufia A. , Chuklanov Anton P. , Bukharaev Anastas A. , Soldatov Dmitry V.
Published: March 2012

The ability of highly ordered tripeptide structures to keep or change their morphology in contact with organic vapors was studied. A thin film of tripeptide l‐leucyl‐l‐leucyl‐l‐leucine (LLL) was prepared having microcrystals and nanocrystals on its surface, which are stable upon vacuum drying but become objects of selective morphology change after a contact with vapors of organic solvents. Fine separate LLL crystals and their agglomerates of submicron and larger dimensions were observed by atomic force microscopy and scanning electron microscopy. After saturation with guest vapors, these crystals can remain intact or change their morphology with the increase in size or complete destruction depending on the guest molecular structure. The crystals completely lose their shape after the binding of pyridine vapors. The other studied guests produce much smaller transformations or have no effect on crystal morphology despite being sorbed by solid LLL, which was shown using quartz crystal microbalance sensor. The observed size‐exclusion effect for guest sorption by LLL was found to be broken by the same guests that can change the initial crystal shape. This helps to explain the morphology changes of LLL crystals after the guest sorption and release. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
6‐Gingerol Induces Apoptosis through Lysosomal‐Mitochondrial Axis in Human Hepatoma G2 Cells
Authors: Yang Guang , Wang Shaopeng , Zhong Laifu , Dong Xu , Zhang Wenli , Jiang Liping , Geng Chengyan , Sun Xiance , Liu Xiaofang , Chen Min , Ma Yufang
Published: March 2012

6‐Gingerol, a major phenolic compound derived from ginger, has been known to possess anticarcinogenic activities. However, the mechanisms are not well understood. In our previous study, it was demonstrated that lysosome and mitochondria may be the primary targets for 6‐gingerol in HepG2 cells. Therefore, the aim was to evaluate lysosome‐mitochondria cross‐signaling in 6‐gingerol‐induced apoptosis. Apoptosis was detected by Hoechst 33342 and TUNEL assay after 24 h treatment, and the destabilization of lysosome and mitochondria were early upstream initiating events. This study showed that cathepsin D played a crucial role in the process of apoptosis. The release of cathepsin D to the cytosol appeared to be an early event that preceded the release of cytochrome c from mitochondria. Moreover, inhibition of cathepsin D activity resulted in suppressed release of cytochrome c. To further determine the involvement of oxidative stress in 6‐gingerol‐induced apoptosis, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH) were examined. Taken together, these results suggest that cathepsin D may be a positive mediator of 6‐gingerol induced apoptosis in HepG2 cells, acting upstream of cytochrome c release, and the apoptosis may be associated with oxidative stress. Copyright © 2012 John Wiley & Sons, Ltd.
Schisandra chinensis Prevents Hepatic Lipid Peroxidation and Oxidative Stress in Rats Subjected to Heat Environmental Stress
Authors: Kim Kui‐Jin , Yoon Kye‐Yoon , Hong Hee‐Do , Lee Boo‐Yong
Published: March 2012

Increases in temperature cause a proliferation of heat‐stress‐related disorders by disrupting the body's homeostasis system, particularly when excessive levels of reactive oxygen species disrupt the balance of antioxidant defence systems. Thus, controlling oxidative stress is important for the regulation of body homeostasis. Schisandra chinensis (SC) has a potential effect on antioxidants and is resistant to high temperatures. However, the mechanism of SC during heat stress is unclear. Therefore, we evaluated the effect of SC on heat stress by performing several bioactive genetic assays on Sprague Dawley (SD) rats. The results demonstrated that heat stress significantly increased in heat‐stress‐related gene expression whereas it was dramatically reduced in the gene expression of the SC group. The genes related to oxidative stress were also significantly suppressed in the SC group compared with those of the heat stress group. Furthermore, there was a greater decrease in the MDA content of the SD rats in the orally administered SC group than in the heat exposure group. Thus, we demonstrate that SC has a protective effect on heat stress as a result of its strong antioxidant properties and the prevention of lipid peroxidation. Copyright © 2012 John Wiley & Sons, Ltd.
A spatio‐temporal absorbing state model for disease and syndromic surveillance
Authors: Heaton Matthew J. , Banks David L. , Zou Jian , Karr Alan F. , Datta Gauri , Lynch James , Vera Francisco
Published: March 2012

Reliable surveillance models are an important tool in public health because they aid in mitigating disease outbreaks, identify where and when disease outbreaks occur, and predict future occurrences. Although many statistical models have been devised for surveillance purposes, none are able to simultaneously achieve the important practical goals of good sensitivity and specificity, proper use of covariate information, inclusion of spatio‐temporal dynamics, and transparent support to decision‐makers. In an effort to achieve these goals, this paper proposes a spatio‐temporal conditional autoregressive hidden Markov model with an absorbing state. The model performs well in both a large simulation study and in an application to influenza/pneumonia fatality data. Copyright © 2012 John Wiley & Sons, Ltd.
Writing Workshop In Preschool
Authors: King Kelly A.
Published: March 2012

Preschoolers may be novices in the area of writing but, as this article highlights, they are indeed writers. In a year‐long ethnography of preschoolers during structured writing time the teacher/researcher explored how students adapted to a writing workshop format. Students participated in daily journal writing and sharing, and weekly conference time. This article shows how students used the classroom structure to demonstrate their growing understanding about what it means to be a writer; and how the teacher observed student behavior in order to adapt writing time to best meet the needs of her students.
Factoring AAVE Into Reading Assessment and Instruction
Authors: Wheeler Rebecca , Cartwright Kelly B. , Swords Rachel
Published: March 2012

In our increasingly diverse schools, students bring diverse ways of speaking to the classroom. In turn, as features from students’ home language varieties transfer into their readings of texts, teachers’ assessment and intervention plans may be directly affected. If teachers conflate dialect influence with reading error in Standard English, they may inaccurately assess students’ reading performance and propose inappropriate instructional plans. In this article we provide insights into the ways African American Vernacular English (AAVE) may influence reading assessments and subsequent instructional decisions. Additionally, we describe an intervention – contrastive analysis and code‐switching – designed to help students become metacognitively aware of the multiple language varieties at work in their worlds. Newly aware of the structures and uses of home and school English, students learn to strategically choose the language variety appropriate to the context. In this way, factoring dialect into reading assessment and intervention results in improved literacy performance.
Breast Cancer Local Therapy: What Is Its Effect on Mortality?
Authors: Benson John R. , Teo Katy A. T.
Published: March 2012

Until recently, the concept of biological predeterminism appeared pre‐eminent and a worthy successor to the Halstedian doctrine of centrifugal spread of cancer. However, evidence has now emerged from clinical trials to cast doubt on the universal application of this concept to breast tumors. Prevention of local recurrence can save lives, local control does matter, and rates of local recurrence should be minimized in the first 5 years. In up to one quarter of cases of local recurrence the locally recurring disease will be a determinant and not simply a marker of risk for distant relapse and death. Both types of local recurrence are manifestations of the same biological processes and reflect intrinsic behavior of the tumor. This principle applies to reduction in local relapse from both adjuvant radiotherapy and surgical modalities.
Prolactin Promotes Hepatocellular Carcinoma through Janus Kinase 2
Authors: Yeh Yao‐Tsung , Lee King‐Teh , Tsai Chia‐Jung , Chen Yu‐Jie , Wang Shen‐Nien
Published: March 2012

Background

Hepatocelluar carcinoma (HCC) is one human cancer with obvious gender disparity. This study investigated the association of aberrant prolactin levels with HCC risk and the potential impacts on HCC of the prolactin receptor (PRLR)/Janus kinase 2 (JAK2) signaling.

Methods

Serum prolactin of 63 HCC patients and 162 subjects without HCC was measured by radioimmunoassay. The expressions of PRLR and phosphorylated JAK2 (p‐JAK2) in 82 retrospectively collected HCC specimens were evaluated by immunohistochemistry and further incorporated into the survival analysis. The immunoblotting and proliferation assays were used to analyze the effects of PRLR/JAK2 signaling on liver cancer cells with prolactin treatment.

Results

Serum prolactin level was significantly higher in HCC patients than in controls. Hepatocellular carcinoma patients with high p‐JAK2 expression had a significantly higher postoperative risk than those with low p‐JAK2 expression. Moreover, results from the multivariate analysis indicated the prognostic role of p‐JAK2 expression with respect to overall survival in HCC patients. In addition, the Kaplan–Meier survival curve showed that high p‐JAK2 expression was associated with poor survival in HCC patients with high PRLR expression. The immunoblotting assay showed that prolactin induced the expression of both p‐JAK2 and cyclin D1 in Hep‐G2 cells. Importantly, the proliferative effects induced by prolactin could be effectively attenuated by adding AG490, a JAK2 inhibitor.

Conclusions

Increased circulating prolactin was found in HCC patients and high p‐JAK2 expression could predict poor overall survival in those patients expressing high PRLR. In addition, prolactin contributed to the proliferation of liver cancer cells through PRLR/JAK2 signaling.
Ectopic pregnancy: when is expectant management safe?
Authors: Rodrigues Sharon P. , de Burlet Kirsten J. , Hiemstra Ellen , Twijnstra Andries R. H. , van Zwet Erik W. , Trimbos-Kemper Trudy C. M. , Jansen Frank W.
Published: March 2012

This study was conducted to evaluate expectant management in asymptomatic patients with an initial serum beta-hCG titer of <2,500 IU/l and to determine the independent ability of initial serum beta-hCG titers and trend of serum beta-hCG to predict successful expectant management. A cohort of patients (N = 418) with suspected ectopic pregnancy (EP) between January 1991 and July 2008 is described. Three groups were defined: group I (n = 182), immediate surgical intervention (<24 h); group IIa (n = 130), unsuccessful expectant management (surgical intervention during follow-up), and group IIb (n = 99), successful expectant management (spontaneous regression of trophoblast). Hospital protocol was not complied in 35 cases (Table 1). Beta-hCG levels >3,000 IU/l occur in our expectant management group; however, none of these cases were successful. Unnecessary surgery was prevented in 14% (n = 7) of asymptomatic patients with initial beta-hCG of >2,000 IU/l. The success rate of expectant management was 49%, without a rise in complication rate or number of acute cases. In conclusion, the initial serum beta-hCG cutoff level of 2,000 IU/l is not a rigid upper limit for accepting expectant management in suspected EP and best practice is case specific. In asymptomatic patients, the serum beta-hCG cutoff level of at least 2,500 IU/l can be used for expectant management. This cutoff could be higher, but interpretation is limited due to censure in follow-up inherent to the predefined clinical protocol. There is no gain in including patients for expectant management with initial serum beta-hCG level >3,000 IU/l.
Progress in understanding 2‐hydroxyglutaric acidurias
Authors: Kranendijk Martijn , Struys Eduard A. , Salomons Gajja S. , Van der Knaap Marjo S. , Jakobs Cornelis
Published: March 2012

The organic acidurias d‐2‐hydroxyglutaric aciduria (D‐2‐HGA), l‐2‐hydroxyglutaric aciduria (L‐2‐HGA), and combined d,l‐2‐hydroxyglutaric aciduria (D,L‐2‐HGA) cause neurological impairment at young age. Accumulation of d‐2‐hydroxyglutarate (D‐2‐HG) and/or l‐2‐hydroxyglutarate (L‐2‐HG) in body fluids are the biochemical hallmarks of these disorders. The current review describes the knowledge gathered on 2‐hydroxyglutaric acidurias (2‐HGA), since the description of the first patients in 1980. We report on the clinical, genetic, enzymatic and metabolic characterization of D‐2‐HGA type I, D‐2‐HGA type II, L‐2‐HGA and D,L‐2‐HGA, whereas for D‐2‐HGA type I and type II novel clinical information is presented which was derived from questionnaires.
Subjective well-being and exercise in the second half of life: a critical review of theoretical approaches
Authors: Lehnert Katrin , Sudeck Gorden , Conzelmann Achim
Published: March 2012

Research has shown repeatedly that the “feeling better” effect of exercise is far more moderate than generally claimed. Examinations of subgroups in secondary analyses also indicate that numerous further variables influence this relationship. One reason for inconsistencies in this research field is the lack of adequate theoretical analyses. Well-being output variables frequently possess no construct definition, and little attention is paid to moderating and mediating variables. This article integrates the main models in an overview and analyzes how secondary analyses define well-being and which areas of the construct they focus on. It then applies a moderator and/or mediator framework to examine which person and environmental variables can be found in the existing explanatory approaches in sport science and how they specify the influence of these moderating and mediating variables. Results show that the broad understanding of well-being in many secondary analyses makes findings difficult to interpret. Moreover, physiological explanatory approaches focus more on affective changes in well-being, whereas psychological approaches also include cognitive changes. The approaches focus mostly on either physical or psychological person variables and rarely combine the two, as in, for example, the dual-mode model. Whereas environmental variables specifying the treatment more closely (e.g., its intensity) are comparatively frequent, only the social support model formulates variables such as the framework in which exercise is presented. The majority of explanatory approaches use simple moderator and/or mediator models such as the basic mediated (e.g., distraction hypothesis) or multiple mediated (e.g., monoamine hypotheses) model. The discussion draws conclusions for future research.
BM61 of Bombyx mori nucleopolyhedrovirus: Its involvement in the egress of nucleocapsids from the nucleus
Authors: Shen Hongxing , Chen Keping
Published: March 2012

All lepidopteran baculovirus genomes sequenced encode a homolog of the Bombyx mori nucleopolyhedrovirus orf61 gene (Bm61). To determine the role of Bm61 in the baculoviral life cycle, we constructed a Bm61 knockout virus and characterized it in cells. We observed that the Bm61 deletion bacmid led to a defect in production of infectious budded virus (BV). Quantitative PCR analysis of BV in the media culturing the transfected cell indicated that BV was not produced due to Bm61 deletion. Electron microscope analysis showed that in the knockout of Bm61, nucleocapsids were not transported from the nucleus to the cytoplasm. From these results we concluded that BM61 is required in the BV pathway for the egress of nucleocapsids from the nucleus to the cytoplasm.
Visions of the People
Authors: Joyce Patrick
Published: March 2012

This is a study of how the labouring poor of nineteenth-century industrial England saw the social order of which they were a part. It attacks orthodoxies and sets up new questions by attending to a wide range of contemporary experience, from politics and work to language and art.
Digital Satellite Navigation and Geophysics
Authors: Petrovski Ivan G. , Tsujii Toshiaki
Published: March 2012

Bridge the gap between theoretical education and practical work experience with this hands-on guide to GNSS, which features:
• A clear, practical presentation of GNSS theory, with emphasis on GPS and GLONASS
• All the essential theory behind software receivers and signal simulators
• Key applications in navigation and geophysics, including INS aiding, scintillation monitoring, earthquake studies and more
• Physical explanations of various important phenomena, including the similarity of code delay and phase advance of GNSS signals, and negative cross-correlation between scintillation intensity and phase variations.
Whether you are a practising engineer, a researcher or a student, you will gain a wealth of insights from the authors' 25 years of experience. You can explore numerous practical examples and case studies and get hands-on user experience with a bundled real-time software receiver, signal simulator and a set of signal data, enabling you to create your own GNSS lab for research or study.