bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B‐related serological events in hematopoietic stem cell transplant patients and efficacy of lamivudine prophylaxis against reactivation
Authors: Gupta Alok , Punatar Sachin , Gawande Jayant , Bagal Bhausaheb , Mathew Libin , Bhat Vivek , Kannan Sadhana , Khattry Navin
Published: February 2015

Reactivation of remote hepatitis B infection (RHBI) is an important cause of morbidity in hematopoietic cell transplant (HCT) patients. We analyzed the prevalence of RHBI in 205 patients who underwent HCT in our centre, serological events related to hepatitis B virus (HBV) reactivation and role of lamivudine prophylaxis in HCT patients with RHBI. The prevalence of RHBI was 14% (28/205 patients). Of these 28 patients, 15 received lamivudine prophylaxis (14 anti‐HBcIgG positive and 1 only anti‐HBs positive) while 13 did not receive lamivudine prophylaxis (12 anti‐HBs positive and 1 anti‐HBcIgG positive). None in prophylaxis group developed HBV reactivation while 12 of 13 in no‐prophylaxis group reactivated (P < 0.001). The rate of HBV reactivation was 10% (21/205 patients), which included 9 patients with no evidence of RHBI pre‐transplant. We conclude that lamivudine prophylaxis protects against HBV reactivation in HCT patients with evidence of RHBI. Lamivudine prophylaxis should be used not only in patients with anti‐HBcIgG positivity but also in those with isolated anti‐HBs positivity pre‐transplant given the high rate of HBV reactivation in these patients. HBV serology cannot identify all cases with RHBI and therefore does not preclude HBV reactivation post‐transplant. Copyright © 2015 John Wiley & Sons, Ltd.
Becoming a Working Mother: Managing Identity and Efficacy Uncertainties During Resocialization
Authors: Ladge Jamie J. , Greenberg Danna N.
Published: February 2015

The work reentry period following the birth of a first child is a time of uncertainty for a professional woman. During reentry, a new mother is often questioning who she is and how effective she can be as a mother and working professional. In this study, we conceptualize reentry as a period of resocialization as we explore the first‐time mother's changing self‐concept during this time. Specifically, we develop a model that explores the identity and efficacy uncertainties that women experience during resocialization. This model draws attention to the influence organizational context has on the degree of uncertainty women experience and to the adjustment tactics women engage to manage their identity and efficacy uncertainty. We discuss the implications these findings have for both socialization research and work‐life theory and practice. © 2015 Wiley Periodicals, Inc.
Transactional Patterns of Maternal Depressive Symptoms and Mother–Child Mutual Negativity in an Adoption Sample
Authors: Roben Caroline K. P. , Moore Ginger A. , Cole Pamela M. , Molenaar Peter , Leve Leslie D. , Shaw Daniel S. , Reiss David , Neiderhiser Jenae M.
Published: February 2015

Transactional models of analysis can examine both moment‐to‐moment interactions within a dyad and dyadic patterns of influence across time. This study used data from a prospective adoption study to test a transactional model of parental depressive symptoms and mutual negativity between mother and child over time, utilizing contingency analysis of second‐by‐second behavioral data. To consider both genetic and environmental influences on mutual negativity, depressive symptoms were examined in both adoptive and birth mothers. Adoptive mother depressive symptoms at 9 months increased the likelihood that, at 18 months, children reacted negatively to their mothers' negative behavior, which in turn predicted higher levels of adoptive mother depressive symptoms at 27 months, suggesting that over time, mothers' depressive symptoms influence and are influenced by moment‐to‐moment mutual negativity with their toddlers. Birth mother depressive symptoms moderated the association between mutual negativity at 18 months and adoptive mother depressive symptoms at 27 months, suggesting a child‐driven contribution to maternal depressive symptoms that can be measured by a genetic sensitivity. Copyright © 2015 John Wiley & Sons, Ltd.
A Half‐Century Odyssey in the Realm of Reactive Intermediates
Authors: Moss Robert A.
Published: February 2015

Through a retrospective examination of the author’s half‐century immersion in physical organic chemistry, an attempt is made to identify some broader currents in the field. Among these are the cyclical nature of physical organic chemistry, the persistence of research themes, the driving force of new instrumentation, paradigm shifts in theory, greater computational power, enhanced time resolution of experiments, and the export of mechanism‐based analysis to other foci of contemporary science.
Structural Characterization of Frustrated Lewis Pairs and Their Reaction Products Using Modern Solid‐State NMR Spectroscopy Techniques
Authors: Wiegand Thomas , Siedow Melanie , Eckert Hellmut , Kehr Gerald , Erker Gerhard
Published: February 2015

Frustrated Lewis pair (FLP) chemistry has provided a new strategy for small‐molecule binding and/or catalytic activation. The most prominent FLPs are based on intramolecular phosphaneborane adducts, the catalytic properties of which can be tailored over wide ranges of reactivity and selectivity. Advanced solid‐state NMR spectroscopic techniques, together with DFT calculations, can provide new structural insights in these systems. This review illustrates the utility of 31P and 11B NMR chemical shifts, 11B electric field gradient tensors, and 31P11B indirect and direct dipoledipole interactions for characterizing intramolecular boranephosphane FLPs. We demonstrate the potential of this method to 1) quantify the extent of boronphosphorus bonding interactions (and hence, the “degree of frustration”); 2) reveal specific structural details (i.e., boronphosphorus distances and other local geometric aspects) related to their catalytic activities; and (3) characterize products of FLP reactions with regard to molecular structure, stereochemistry, and aggregation properties in terms of internuclear distances, bonding connectivities, and orientational parameters.
Happier together. Social cohesion and subjective well‐being in Europe
Authors: Delhey Jan , Dragolov Georgi
Published: February 2015

Despite mushrooming research on “social” determinants of subjective well‐being (SWB), little is known as to whether social cohesion as acollectiveproperty is among the keysocietalconditions for human happiness. This article fills this gap in investigating the importance of living in a cohesive society for citizens'SWB. For 27 European Union countries, it combines the newly developedBertelsmann Foundation's Cohesion Indexwith individual well‐being data on life evaluation and psychological functioning as surveyed in the recentEuropean Quality of Life Survey.The main results from multi‐level analyses are as follows. First, Europeans are indeed happier and psychologically healthier in more cohesive societies. Second, all three core domains of cohesion increase individuals'SWB. Third, citizens in the more affluent part of Europe feel the positivity of social cohesion more consistently than those in the less affluent part. Finally, within countries, cohesion is good for theSWBof resource‐rich and resource‐poor groups alike. Our findings also shed new light on the ongoing debate on economic progress and quality of life: what makes citizenries of affluent societies happier is, in the first place, their capacity to create togetherness and solidarity among their members—in other words, cohesion.
Looking good or doing good? Motivations for organisational citizenship behaviour in Turkish versus South Korean collectivists
Authors: Alabak Merve , Peker Müjde , Booth Robert W.
Published: February 2015

The purpose of this article is to explore potential motivations to perform organisational citizenship behaviour (OCB) in collectivistic Turkish and South Korean societies. Although collectivism has been proposed as a predictor of OCB, previous research has not fully explored the possibility that collectivistic individuals' OCB may result from their self‐oriented motives (i.e. social desirability concerns) or their future‐oriented motives (i.e. long‐term orientation concerns). We predicted that OCB stems from social desirability concerns among Turkish collectivists, meaning it is used for maintaining a positive image within the organisation. However, for South Korean collectivists, we predicted that OCB stems from their long‐term orientation concerns, meaning it is used to make the organisation better. The results were in line with our predictions, and the findings are discussed in terms of their implications for firms in collectivistic societies.
SALTMED Model as an Integrated Management Tool for Water, Crop, Soil and N‐Fertilizer Water Management Strategies and Productivity: Field and Simulation Study
Authors: Ragab R. , Battilani A. , Matovic G. , Stikic R. , Psarras G. , Chartzoulakis K.
Published: February 2015

This paper is a follow‐up from a paper which described the SALTMED model. In this paper the focus is on the model application, using data of tomato and potato from field experiments in Italy, Greece (Crete) and Serbia. Drip full irrigation, drip deficit irrigation, drip as partial root drying (PRD), sprinkler and furrow irrigation were used in the 3‐yr experiment between 2006 and 2008. In drip‐irrigated experiments, the drip line was 10–12 cm below the surface. Dry matter, final yield, soil moisture and soil nitrogen were successfully simulated. The study showed that there is a great potential for saving water when using subsurface drip, PRD or drip deficit irrigation compared with sprinkler and furrow irrigation. Depending on the crop and irrigation system, the amount of fresh water that can be saved could vary between 14 and 44%. PRD and deficit drip irrigation have proved to be the most efficient water application strategies with the highest water productivity. Copyright © 2015 John Wiley & Sons, Ltd.
The effect of a methyl‐deficient diet on the global DNA methylation and the DNA methylation regulatory pathways
Authors: Takumi Shota , Okamura Kazuyuki , Yanagisawa Hiroyuki , Sano Tomoharu , Kobayashi Yayoi , Nohara Keiko
Published: February 2015

Methyl‐deficient diets are known to induce various liver disorders, in which DNA methylation changes are implicated. Recent studies have clarified the existence of the active DNA demethylation pathways that start with oxidization of 5‐methylcytosine (5meC) to 5‐hydroxymethylcytosine by ten‐eleven translocation (Tet) enzymes, followed by the action of base–excision–repair pathways. Here, we investigated the effects of a methionine–choline‐deficient (MCD) diet on the hepatic DNA methylation of mice by precisely quantifying 5meC using a liquid chromatography–electrospray ionization–mass spectrometry and by investigating the regulatory pathways, including DNA demethylation. Although feeding the MCD diet for 1 week induced hepatic steatosis and lower level of the methyl donor S‐adenosylmethionine, it did not cause a significant reduction in the 5meC content. On the other hand, the MCD diet significantly upregulated the gene expression of the Tet enzymes, Tet2 and Tet3, and the base–excision–repair enzymes, thymine DNA glycosylase and apurinic/apyrimidinic‐endonuclease 1. At the same time, the gene expression of DNA methyltransferase 1 and a, was also significantly increased by the MCD diet. These results suggest that the DNA methylation level is precisely regulated even when dietary methyl donors are restricted. Methyl‐deficient diets are well known to induce oxidative stress and the oxidative‐stress‐induced DNA damage, 8‐hydroxy‐2′‐deoxyguanosine (8OHdG), is reported to inhibit DNA methylation. In this study, we also clarified that the increase in 8OHdG number per DNA by the MCD diet is approximately 10 000 times smaller than the reduction in 5meC number, suggesting the contribution of 8OHdG formation to DNA methylation would not be significant. Copyright © 2015 John Wiley & Sons, Ltd.
Heterozygous p53 knockout mouse model for dehydropyrrolizidine alkaloid‐induced carcinogenesis
Authors: Brown Ammon W. , Stegelmeier Bryan L. , Colegate Steven M. , Panter Kip E. , Knoppel Edward L. , Hall Jeffery O.
Published: February 2015

Dehydropyrrolizidine alkaloids (DHPA) are a large, structurally diverse group of plant‐derived protoxins that are potentially carcinogenic. With worldwide significance, these alkaloids can contaminate or be naturally present in the human food supply. To develop a small animal model that may be used to compare the carcinogenic potential of the various DHPAs, male heterozygous p53 knockout mice were administered a short‐term treatment of riddelliine 5, 15 or 45 mg kg–1 bodyweight day–1 by oral gavage for 14 days, or dosed a long‐term treatment of riddelliine 1 mg kg–1 bodyweight day–1 in pelleted feed for 12 months. Exposure to riddelliine increased the odds of tumor development in a dose‐responsive manner (odds ratio 2.05 and Wald 95% confidence limits between 1.2 and 3.4). The most common neoplastic process was hepatic hemangiosarcoma, which is consistent with published lifetime rodent riddelliine carcinogenesis studies. Angiectasis (peliosis hepatis) and other previously unreported lesions were also identified. The results of this research demonstrate the utility of the heterozygous p53 knockout mouse model for further investigation of comparative carcinogenesis of structurally and toxicologically different DHPAs and their N‐oxides. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Extended culture of macrophages from different sources and maturation results in a common M2 phenotype
Authors: Chamberlain Lisa M. , Holt‐Casper Dolly , Gonzalez‐Juarrero Mercedes , Grainger David W.
Published: February 2015

Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign‐body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely used in short‐term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte–macrophage cell types have intrinsic in vitro culture‐specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary‐derived origins were cultured for 21 days on model polymer biomaterials. Cell type‐based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development toward an M2 phenotype via up‐regulation of the macrophage mannose receptor for all cell types following 21‐day extended culture. Significantly, implanted biomaterials experiencing the foreign‐body response and encapsulation in vivo often elicit a shift toward an analogous M2 macrophage phenotype. In vitro “default” of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized, but has important implications to in vitro modeling of in vivo host response. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2864–2874, 2015.
Computational Simulation Techniques to Understand Rifampicin Resistance Mutation (S425L) of rpoB in M. leprae
Authors: Nisha J. , Shanthi V.
Published: February 2015

Mycobacterium leprae, the etiologic agent of leprosy, is non‐cultivable in vitro. Consequently, the assessment of antibiotic activity against M. leprae hinge mainly upon the time consuming mouse footpad system. As M. leprae develops resistance against most of the drugs, the evolution of new long acting antimycobacterial compounds stand in need for leprosy control. The rpoB of M. leprae is the target of antimycobacterial drug, rifampicin. Recently, cases were reported that rpoB mutation (S425L) became resistant to rifampicin and the mechanism of resistance is still not well understood. The present study is aimed at studying the molecular and structural mechanism of the rifampicin binding to both native and mutant rpoB through computational approaches. From molecular docking, we demonstrated the stable binding of rifampicin through two hydrogen bonding with His420 residue of native than with mutant rpoB where one hydrogen bonding was found with Ser406. The difference in binding energies observed in the docking study evidently signifies that rifampicin is less effective in the treatment of patients with S425L variant. Moreover, the molecular dynamics studies also highlight the stable binding of rifampicin with native than mutant (S425L) rpoB. J. Cell. Biochem. 116: 1278–1285, 2015. © 2015 Wiley Periodicals, Inc.
Vitamin D Control of Hematopoietic Cell Differentiation and Leukemia
Authors: Studzinski George P. , Harrison Jonathan S. , Wang Xuening , Sarkar Surojit , Kalia Vandana , Danilenko Michael
Published: February 2015

It is now well known that in the mammalian body vitamin D is converted by successive hydroxylations to 1,25‐dihydroxyvitamin D (1,25D), a steroid‐like hormone with pleiotropic properties. These include important contributions to the control of cell proliferation, survival and differentiation, as well as the regulation of immune responses in disease. Here, we present recent advances in current understanding of the role of 1,25D in myelopoiesis and lymphopoiesis, and the potential of 1,25D and analogs (vitamin D derivatives; VDDs) for the control of hematopoietic malignancies. The reasons for the unimpressive results of most clinical studies of the therapeutic effects of VDDs in leukemia and related diseases may include the lack of a precise rationale for the conduct of these studies. Further, clinical trials to date have generally used extremely heterogeneous patient populations and, in many cases, small numbers of patients, generally without controls. Although low calcemic VDDs have been used and combined with agents that can increase the leukemia cell killing or differentiation effects in acute leukemias, the sequencing of agents used for combination therapy should to be more clearly delineated. Most importantly, it is recommended that in future clinical trials the rationale for the basis of the enhancing action of drug combinations should be clearly articulated and the effects on anticancer immunity should also be evaluated. J. Cell. Biochem. 116: 1500–1512, 2015. © 2015 Wiley Periodicals, Inc.
An Optimal Medium Supplementation Regimen for Initiation of Hepatocyte Differentiation in Human Induced Pluripotent Stem Cells
Authors: Tomizawa Minoru , Shinozaki Fuminobu , Motoyoshi Yasufumi , Sugiyama Takao , Yamamoto Shigenori , Ishige Naoki
Published: February 2015

Human induced pluripotent stem (hiPS) cells are an ideal source for hepatocytes. Glucose and arginine are necessary for cells to survive. Hepatocytes have galactokinase (GALK), which metabolizes galactose for gluconeogenesis, and ornithine transcarbamylase (OTC), which converts ornithine to arginine in the urea cycle. Hepatocyte selection medium (HSM) lacks both glucose and arginine, but contains galactose and ornithine. Although human primary hepatocytes survive in HSM, all the hiPS cells die in 3 days. The aim of this study was to modify HSM so as to initiate hepatocyte differentiation in hiPS cells within 2 days. Hepatocyte differentiation initiating medium (HDI) was prepared by adding oncostatin M (10 ng/ml), hepatocyte functional proliferation inducer (10 nM), 2,2'‐methylenebis (1,3‐cyclohexanedione) (M50054) (100 μg/ml), 1× non‐essential amino acid, 1× sodium pyruvate, nicotinamide (1.2 mg/ml), L‐proline (30 ng/ml), and L‐glutamine (0.3 mg/ml) to HSM. HiPS cells (201B7 cells) were cultured in HDI for 2 days. RNA was isolated, used as template for cDNA, and subjected to real‐time quantitative polymerase chain reaction. Alpha‐fetoprotein, γ‐glutamyl transpeptidase, and delta‐like 1 were upregulated. Expression of albumin was not observed. Expression of transcription factors specific to hepatocytes was upregulated. The expression of GALK2, OTC, and CYP3A4 were increased. In conclusion, differentiation of 201B7 cells to hepatoblast‐like cells was initiated in HDI. Limitations were small number of cells were obtained, and the cells with HDI were not mature hepatocytes. J. Cell. Biochem. 116: 1479–1489, 2015. © 2015 Wiley Periodicals, Inc.
Enhanced conformational sampling method for proteins based on the TaBoo SeArch algorithm: Application to the folding of a mini‐protein, chignolin
Authors: Harada Ryuhei , Takano Yu , Shigeta Yasuteru
Published: February 2015

The conformational samplings are indispensible for obtaining reliable canonical ensembles, which provide statistical averages of physical quantities such as free energies. However, the samplings of vast conformational space of biomacromolecules by conventional molecular dynamics (MD) simulations might be insufficient, due to their inadequate accessible time‐scales for investigating biological functions. Therefore, the development of methodologies for enhancing the conformational sampling of biomacromolecules still remains as a challenging issue in computational biology. To tackle this problem, we newly propose an efficient conformational search method, which is referred as TaBoo SeArch (TBSA) algorithm. In TBSA, an inverse energy histogram is used to select seeds for the conformational resampling so that states with high frequencies are inhibited, while states with low frequencies are efficiently sampled to explore the unvisited conformational space. As a demonstration, TBSA was applied to the folding of a mini‐protein, chignolin, and automatically sampled the native structure (Cα root mean square deviation < 1.0 Å) with nanosecond order computational costs started from a completely extended structure, although a long‐time 1‐µs normal MD simulation failed to sample the native structure. Furthermore, a multiscale free energy landscape method based on the conformational sampling of TBSA were quantitatively evaluated through free energy calculations with both implicit and explicit solvent models, which enable us to find several metastable states on the folding landscape. © 2015 Wiley Periodicals, Inc.
A comparative examination of odontogenic gene expression in both toothed and toothless amniotes
Authors: Lainoff Alexis J. , Moustakas‐Verho Jacqueline E. , Hu Diane , Kallonen Aki , Marcucio Ralph S. , Hlusko Leslea J.
Published: February 2015

A well‐known tenet of murine tooth development is that BMP4 and FGF8 antagonistically initiate odontogenesis, but whether this tenet is conserved across amniotes is largely unexplored. Moreover, changes in BMP4‐signaling have previously been implicated in evolutionary tooth loss in Aves. Here we demonstrate thatBmp4, Msx1, andMsx2expression is limited proximally in the red‐eared slider turtle (Trachemys scripta) mandible at stages equivalent to those at which odontogenesis is initiated in mice, a similar finding to previously reported results in chicks. To address whether the limited domains in the turtle and the chicken indicate an evolutionary molecular parallelism, or whether the domains simply constitute an ancestral phenotype, we assessed gene expression in a toothed reptile (the American alligator,Alligator mississippiensis) and a toothed non‐placental mammal (the gray short‐tailed opossum,Monodelphis domestica). We demonstrate that theBmp4domain is limited proximally inM. domesticaand that theFgf8domain is limited distally inA. mississippiensisjust preceding odontogenesis. Additionally, we show thatMsx1andMsx2expression patterns in these species differ from those found in mice. Our data suggest that a limitedBmp4domain does not necessarily correlate with edentulism, and reveal that the initiation of odontogenesis in non‐murine amniotes is more complex than previously imagined. Our data also suggest a partially conserved odontogenic program inT. scripta, as indicated by conservedPitx2, Pax9, andBarx1expression patterns and by the presence of aShh‐expressing palatal epithelium, which we hypothesize may represent potential dental rudiments based on the Testudinata fossil record.J. Exp. Zool. (Mol. Dev. Evol.) 324B: 255–269, 2015. © 2015 Wiley Periodicals, Inc.
Clinical features of pancreatic neuroendocrine tumors
Authors: Grozinsky‐Glasberg Simona , Mazeh Haggi , Gross David J.
Published: February 2015

Pancreatic neuroendocrine tumors (PNETs), also known as islet cell tumors, are rare neoplasms that arise in the endocrine tissues of the pancreas. Most of pancreatic NETs (50–75%) are nonfunctioning (not associated with a hormonal clinical syndrome); however, in up to one third they can secrete a variety of peptide hormones, including insulin, gastrin, glucagon, vasoactive intestinal peptide, somatostatin etc., resulting in rare but unique clinical syndromes. In this article, the clinical features of the different types of PNETs will be reviewed. Other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, as they are covered by other papers in this volume.
Prior pneumococcal and influenza vaccinations and in‐hospital outcomes for community‐acquired pneumonia in elderly veterans
Authors: Li Chenghui , Gubbins Paul O. , Chen Guoqing J.
Published: February 2015

BACKGROUND

Studies of adults hospitalized for community‐acquired pneumonia (CAP) reported better outcomes associated with prior pneumococcal vaccination (PV), suggesting potential additional benefits of PV in hospitalized CAP patients. Influenza (flu) vaccination (FV) could independently/additively improve CAP outcomes in hospitalized patients.

OBJECTIVE

To examine the effect of prior PV and FV on in‐hospital outcomes in elderly veterans hospitalized for CAP.

DESIGN

Retrospective cohort study.

SETTING AND PATIENTS

A total of 6,723 elderly veterans who were admitted to Veterans Affairs hospitals for CAP between October 1, 2002 and September 30, 2003.

INTERVENTION

PV in the 5 years and FV in the 1 year before admission.

MEASUREMENTS

The association of prior PV and/or FV with inpatient mortality and length of stay (LOS) (primary) and risk of any bacteremia and respiratory complications (secondary) were assessed using logistic regressions and generalized linear model, controlling for patient demographic and clinical characteristics.

RESULTS

Prior PV alone was not associated with shortened LOS, or reduced risk of inpatient mortality or respiratory complications. Lower risk of bacteremia was associated with prior PV (odds ratio: 0.66; 95% confidence interval [CI]: 0.48‐0.90). After adjusting for patients' characteristics, risk of inpatient mortality was not statistically significantly different across the vaccination groups, but having had both PV and FV before CAP admission was associated with a 10% reduction in LOS (95% CI: 0.86‐0.95) compared to having had neither vaccinations.

CONCLUSION

Significant survival benefit and improved in‐hospital outcomes may not be expected among CAP‐hospitalized elderly patients with prior PV alone. However, having both PV and FV before CAP admission may reduce LOS. Journal of Hospital Medicine 2015;10:287–293. © 2015 Society of Hospital Medicine
Structural determinants for the interactions between muscarinic toxin 7 and muscarinic acetylcholine receptors
Authors: Xu Jianrong , Zhao Hengyi , Zheng Zhaoxi , Wang Yu , Niu Yinyao , Wang Hao , Xu Jun , Lu Yang , Chen Hongzhuan
Published: February 2015

Muscarinic acetylcholine receptors (mAChRs) have five subtypes and play crucial roles in various physiological functions and pathophysiological processes. Poor subtype specificity of mAChR modulators has been an obstacle to discover new therapeutic agents. Muscarinic toxin 7 (MT7) is a natural peptide toxin with high selectivity for the M1 receptor. With three to five residues substituted, M3, M4, and M5 receptor mutants could bind to MT7 at nanomolar concentration as the M1 receptor. However, the structural mechanisms explaining MT7–mAChRs binding are still largely unknown. In this study, we constructed 10 complex models of MT7 and each mAChR subtype or its mutant, performed molecular dynamics simulations, and calculated the binding energies to investigate the mechanisms. Our results suggested that the structural determinants for the interactions on mAChRs were composed of some critical residues located separately in the extracellular loops of mAChRs, such as Glu4.56, Leu4.60, Glu/Gln4.63, Tyr4.65, Glu/Asp6.67, and Trp7.35. The subtype specificity of MT7 was attributed to the non‐conserved residues at positions 4.56 and 6.67. These structural mechanisms could facilitate the discovery of novel mAChR modulators with high subtype specificity and enhance the understanding of the interactions between ligands and G‐protein‐coupled receptors. Copyright © 2015 John Wiley & Sons, Ltd.
Selenium speciation in tea by dispersive liquid–liquid microextraction coupled to high‐performance liquid chromatography after derivatization with 2,3‐diaminonaphthalene
Authors: Zhou Qingxiang , Lei Man , Li Jing , Wang Mengyun , Zhao Danchen , Xing An , Zhao Kuifu
Published: February 2015

Selenium is an important element for human health, and it is present in many natural drinks and foods. Present study described a new method using dispersive liquid–liquid microextraction prior to high‐performance liquid chromatography with a UV variable wavelength detector for the determination of the total selenium, Se(IV), Se(VI), and total organoselenium in tea samples. In the procedure, 2,3‐diaminonaphthalene was used as the chelating reagent, 400 μL acetonitrile was used as the disperser solvent and 60 μL chlorobenzene was used as the extraction solvent. The complex of Se(IV) and 2,3‐diaminonaphthalene in the final extracted phase was analyzed by high‐performance liquid chromatography. The factors influencing the derivatization and microextraction were investigated. Under the optimal conditions, the limit of detection was 0.11 μg/L for Se(IV) and the linearity range was in the range of 0.5–40 μg/L. This method was successfully applied to the determination of selenium in four tea samples with spiked recoveries ranging from 91.3 to 100%.
MELDEQ : An alternative Model for End‐Stage Liver Disease score for patients with hepatocellular carcinoma
Authors: Marvin Michael R. , Ferguson Nicole , Cannon Robert M. , Jones Christopher M. , Brock Guy N.
Published: February 2015

Multiple studies have demonstrated an advantage for hepatocellular carcinoma (HCC) patients under the current liver allocation system, such that the United Network for Organ Sharing (UNOS) recently voted in support of a proposal to delay granting Model for End‐Stage Liver Disease (MELD) exception points to all HCC patients for 6 months, independently of a candidate's native MELD score or alpha‐fetoprotein (AFP) level. We obtained UNOS data on adult patients who were added to the wait list between January 22, 2005 and September 30, 2009, and we explored the relationship between HCC, MELD, AFP, and other factors that contribute to not only dropout on the wait list but posttransplant survival as well. The aim was to establish an equivalent Model for End‐Stage Liver Disease (MELDEQ) score for HCC patients that would reduce the disparity in access to transplantation between HCC and non‐HCC patients. We determined risk groups for HCC patients with dropout hazards equivalent to those of non‐HCC patients, and we evaluated projections for HCC wait‐list dropout/transplantation probabilities on the basis of the MELDEQ prioritization scheme. Projections indicate that lower risk HCC patients (MELDEQ ≤ 18) would have dropout probabilities similar to those of non‐HCC patients in the same MELD score range, whereas dropout probabilities for higher risk HCC patients would actually be improved. The posttransplant survival of all HCC risk groups is lower than that of their non‐HCC counterparts, with 1‐year survival of 0.77 (95% CI, 0.70‐0.85) for MELDEQ scores ≥ 31. These results suggest that HCC patients with a combination of a low biochemical MELD score and a low AFP level (MELDEQ ≤ 15) would receive a marked advantage in comparison with patients with chemical MELD scores in a similar range and that a delay of 6 months for listing may be appropriate. In contrast, patients with MELDEQ scores > 15 would likely be adversely affected by a universal 6‐month delay in listing. Liver Transpl 21:612–622, 2015. © 2015 AASLD.
Trace metal imaging in diagnostic of hepatic metal disease
Authors: Susnea Iuliana , Weiskirchen Ralf
Published: February 2015

The liver is the most central organ and the largest gland of the body that influences and controls a variety of metabolic and catabolic processes. It produces inconceivable many essential proteins, is responsible for the recovery of various food components, degrades toxins, mediates the bile production, and is involved in the excretion of unwanted metabolites. Several of these anabolic or catabolic functions of the liver depend on trace elements. These are either integral part of enzymes, cofactors, or act as chemical catalysts. Therefore, a lack of trace elements can lead to organ failure or systemic illness. Conversely, excessive hepatic trace element deposition resulting from genetic disorders, intoxication, extensive dietary supply, or long‐term parenteral nutrition may cause hepatic inflammation, fibrosis, cirrhosis, and even hepatocellular carcinoma. Although specific serum parameters currently allow rough assessment of metal deficit and excess, the precise quantification of hepatic metal content in liver is presently only possible by different titration or staining techniques of biopsy specimens. Recently, novel innovative metal imaging techniques were developed that are on the way to replace these traditional methods. In the present review, we summarize the function of different trace elements in liver health and disease and discuss the present knowledge on how quantitative biometal imaging techniques such as synchrotron X‐ray fluorescence microscopy, secondary ion mass spectrometry, and laser ablation inductively coupled plasma mass spectrometry enrich diagnostics in the detection and quantification of hepatic metal disorders. We will further discuss sample preparation, sensitivity, spatial resolution, specificity, quantification strategies, and potential future applications of metal bioimaging in experimental research and clinical daily routine. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:666–686, 2016
Hodge decomposition for two‐dimensional time‐harmonic Maxwell's equations: impedance boundary condition
Authors: Brenner S. C. , Gedicke J. , Sung L. ‐Y.
Published: February 2015

We extend the Hodge decomposition approach for the cavity problem of two‐dimensional time‐harmonic Maxwell's equations to include the impedance boundary condition, with anisotropic electric permittivity and sign‐changing magnetic permeability. We derive error estimates for aP1finite element method based on the Hodge decomposition approach and present results of numerical experiments that involve metamaterials and electromagnetic cloaking. The well‐posedness of the cavity problem when both electric permittivity and magnetic permeability can change sign is also discussed. Copyright © 2015 John Wiley & Sons, Ltd.
In Search of Strategy
Authors: Hager Mark A. , Brudney Jeffrey L.
Published: February 2015

The canon of volunteer administration contends that adoption of specified practices separates effective from ineffective programs. Alternatively, structural contingency and strategic human resource management theories suggest that managers make adoption decisions based on how organizational circumstances dictate the applicability or efficacy of particular practices. We test propositions that universalistic adoption of “best practices,” contingent adoption of practices, and configurational adoption of bundles of practices are associated with program outcomes of recruitment ease, retention of volunteers, and the net benefits that volunteers bring to organizational operations. With all sets of tests garnering limited empirical support, we conclude that human resource practice in volunteer administration is loosely coupled with outcomes, but that some organizations do—and many more should—manage according to the singular context of their institutional and external environments.
Association between serum soluble corin and obesity in Chinese adults: A cross‐sectional study
Authors: Peng Hao , Zhang Qiu , Shen Hengshan , Liu Yan , Chao Xiangqin , Tian Honggang , Cai Xiaoqin , Jin Jianhua
Published: February 2015

Objective

Corin has been suggested to be associated with obesity by cell‐ and animal‐based studies. However, the association has not yet been studied in populations. Here, the aim was to explore the association in a general population of China.

Methods

This was a cross‐sectional study. Data on demographic information, lifestyle risk factors, and personal medical history were collected; body mass index, waist circumference, and blood pressures were measured; and serum corin, blood lipids, and blood glucose were determined in 2498 participants aged above 30 years.

Results

Log‐transformed corin correlated to body mass index (r = 0.197, P < 0.001) and waist circumference (r = 0.289, P < 0.001). In the risk factor‐adjusted analysis, compared with participants in the lowest quartile of serum corin, participants in the 4th quartile had significantly increased risk of prevalent overweight or obesity (OR = 2.26, 95% CI: 1.67‐3.04) and central obesity (OR = 1.74, 95% CI: 1.30‐2.34). ORs of overweight or obesity and central obesity positively and significantly increased with serum corin levels (P for trend < 0.001).

Conclusions

Serum soluble corin was significantly and positively associated with obesity. Our findings suggested that serum soluble corin may be a marker or risk factor for obesity.
UVA‐shielding silicone/zinc oxide nanocomposite coating for automobile windows
Authors: Zhao Xueying , Li Liyi , Liu Yan , Wong Ching‐Ping
Published: February 2015

Among all types of ultraviolet radiation, UVA rays are the most prevalent and can penetrate clouds and glass. In this article, we report the fabrication of a novel silicone/zinc oxide (ZnO) nanocomposite that has outstanding performance in shielding the harmful UVA light. We prepared wurtzite ZnO nanoparticles of three growth durations and dispersed them in a transparent silicone matrix via solution mixing. Our results exhibit a red shift in the absorption peak of the nanocomposites when compared with ZnO colloidal dispersions and decreasing the growth duration of ZnO nanoparticles could improve the UVA‐shielding properties of the nanocomposite. In addition, the nanocomposite presents good shear adhesion strength over 10.5 MPa on glass substrate. The excellent optical and mechanical properties of the novel nanocomposite make it highly promising for automobile window coatings. POLYM. COMPOS., 37:2053–2057, 2016. © 2015 Society of Plastics Engineers
Visualization of proteomics data using R and Bioconductor
Authors: Gatto Laurent , Breckels Lisa M. , Naake Thomas , Gibb Sebastian
Published: February 2015

Data visualization plays a key role in high‐throughput biology. It is an essential tool for data exploration allowing to shed light on data structure and patterns of interest. Visualization is also of paramount importance as a form of communicating data to a broad audience. Here, we provided a short overview of the application of the R software to the visualization of proteomics data. We present a summary of R's plotting systems and how they are used to visualize and understand raw and processed MS‐based proteomics data.
Superdomains in the protein structure hierarchy: The case of PTP‐C2
Authors: Haynie Donald T. , Xue Bin
Published: February 2015

Superdomain is uniquely defined in this work as a conserved combination of different globular domains in different proteins. The amino acid sequences of 25 structurally and functionally diverse proteins from fungi, plants, and animals have been analyzed in a test of the superdomain hypothesis. Each of the proteins contains a protein tyrosine phosphatase (PTP) domain followed by a C2 domain. Four novel conserved sequence motifs have been identified, one in the PTP domain and three in the C2 domain. All contribute to the PTP‐C2 domain interface in PTEN, a tumor suppressor, and all are more conserved than the PTP signature motif, HCX3(K/R)XR, in the 25 sequences. We show that PTP‐C2 was formed prior to the fungi, plant, and animal kingdom divergence. A superdomain as defined here does not fit the usual protein structure classification system. The demonstrated existence of one superdomain suggests the existence of others.
Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine‐linked antibody drug conjugate
Authors: Marcoux Julien , Champion Thierry , Colas Olivier , Wagner‐Rousset Elsa , Corvaïa Nathalie , Van Dorsselaer Alain , Beck Alain , Cianférani Sarah
Published: February 2015

Antibody–drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM‐MS) for the characterization of trastuzumab emtansine (T‐DM1, Kadcyla®). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)‐positive breast cancer, and combines the anti‐HER2 antibody trastuzumab (Herceptin®), with the cytotoxic microtubule‐inhibiting maytansine derivative, DM1. We show that native MS combined with high‐resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM‐MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T‐DM1.
Ion implantation for isolation of AlGaN/GaN HEMTs using C or Al
Authors: Taube Andrzej , Kamińska Eliana , Kozubal Maciej , Kaczmarski Jakub , Wojtasiak Wojciech , Jasiński Jakub , Borysiewicz Michał A. , Ekielski Marek , Juchniewicz Marcin , Grochowski Jakub , Myśliwiec Marcin , Dynowska Elżbieta , Barcz Adam , Prystawko Paweł , Zając Marcin , Kucharski Robert , Piotrowska Anna
Published: February 2015

In this work, we report on the fabrication of electrical isolation for planar AlGaN/GaN high electron mobility transistors (HEMTs) using Al and C ion implantation. Our methodology was to maintain uniform vacancy concentration (>4 × 1020 cm−3) up to the depth of 0.7 µm for both ion species. Electrical measurements have shown that after implantation, the sheet resistance was 1 × 1011 Ω/□ and increased to 5 × 1013–1 × 1014 Ω/□ after annealing at 400 °C and to 5 × 1012–1 × 1013 Ω/□ after annealing at 600 °C. Further annealing at 800 °C decreased the sheet resistance to 5 × 107 Ω/□ and 1 × 108 Ω/□, respectively for C and Al implantation. Characterization by XRD, Raman and photoluminescence spectroscopy provides evidence that implantation damages the crystal lattice, yielding insulating properties. It is demonstrated that the isolation is stable up to 600 °C. We also demonstrate AlGaN/GaN HEMTs on semi‐insulating Ammono‐GaN substrates working both in DC (IDS = 800 mA/mm) and RF (up to 6.5 GHz) mode with isolation prepared by means of the described approach.
Improvement of strained InGaN solar cell performance with a heavily doped n+‐GaN substrate
Authors: Sumiya Masatomo , Honda Tohru , Sang Liwen , Nakano Yoshitaka , Watanabe Kenji , Hasegawa Fumio
Published: February 2015

We simulated III–V nitride heterojunction solar cells with a Mg‐doped GaN/intrinsic InGaN/Si‐doped GaN structure. We investigated the threshold dislocation density, the carrier lifetime, and the strain in the InGaN active layer. The conversion efficiency was sensitive to carrier lifetime limited by Shockely–Read recombination rather than the dislocation density. The electric field induced by the piezoelectric effect in the InGaN layer on +c polarity GaN was opposite to that in the depletion region. The recombination of photo‐generated carriers in the p‐GaN/i‐InGaN/ n‐GaN solar cell structure took place dominantly at the i/n interface even at 0 V, and the performance was remarkably degraded. It was found that this negative influence of the piezoelectric effect was reduced by a heavy doping of more than 3 × 1019 cm−3 into the n+‐GaN layer at the interface.
Improvements in statistical forecasts of monthly and two‐monthly surface air temperatures using a stratospheric predictor
Authors: Karpechko Alexey Yu.
Published: February 2015

Anomalies in the extratropical stratospheric circulation are known to affect climate at the surface for up to 2 months during winter. Previously, several studies have proposed simple statistical models based on a stratospheric predictor to forecast surface climate; however, none of these studies considered a possibility, nor evaluated the skill, of categorical weather forecasts at individual sites. Here we evaluate the skill of the three‐category (below‐normal, near‐normal and above‐normal) monthly and two‐monthly mean surface air temperature statistical forecasts, both deterministic and probabilistic, which use, as predictors, normalized mean polar cap geopotential height at 150 hPa and mean surface air temperature over the preceding 30‐day period (persistence). We show that, during the period 1957–2013, at several sites influenced by the Northern Annular Mode variability, the monthly and two‐monthly forecasts based on the stratospheric predictor possess a moderate skill in December–March at lead times of several days, but in many cases they only marginally improve forecasts based on persistence only. Nevertheless at some sites in northeastern Europe and northwestern Russia the improvements indicate that statistical climate forecasting at these sites can benefit from addition of stratospheric information. The results of this study further demonstrate usefulness of simple statistical models based on stratospheric predictors, both as a complementary source of forecasts, and as providing benchmarks for evaluating the skill of more complex dynamical systems.
On the mass anomaly of potential vorticity vortices
Authors: Viúdez A.
Published: February 2015

The mass anomaly associated with piecewise constant symmetric potential vorticity (PV) vortices in rotating and stratified fluids is investigated. It is found that the absolute value of this mass anomaly depends linearly on the distance to the vortex centre and is therefore unbounded. This property of PV ball vortices is found under quasi‐geostrophic and semi‐geostrophic approximations, as well as the more general Euler dynamics. To overcome this difficulty, a new class of vortices is introduced. These vortices occupy, in all senses, a limited amount of volume and are therefore bounded. Unlike PV ball vortices, which have homogeneous PV, the new vortices have a central core of continuous PV of one sign and an outer shell of opposite signed PV, such that the amount of PV anomaly is zero.