bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of diversity by somatic mutation in theCamelus dromedariusT‐cell receptor gamma variable domains
Authors: Vaccarelli Giovanna , Antonacci Rachele , Tasco Gianluca , Yang Fengtang , Giordano Luca , El Ashmaoui Hassan M. , Hassanane Mohamed S. , Massari Serafina , Casadio Rita , Ciccarese Salvatrice
Published: September 2012

In jawed vertebrates theV‐(D)‐Jrearrangement is the main mechanism generating limitless variations of antigen‐specific receptors, immunoglobulins (IGs), andT‐cell receptors (TCRs) from few genes. Once the initial diversity is established in primary lymphoid organs, further diversification occurs inIGs by somatic hypermutation, a mechanism from which rearrangedTCRgenes were thought to be excluded. Here, we report the locus organization and expression of theT‐cell receptor gamma (TCRG) genes in theArabian camel (Camelus dromedarius). Expression data provide evidence that dromedary utilizes only twoTCRG V‐Jgenomic arrangements and, as expected,CDR3 contributes the major variability in theVdomain. The data also suggest that diversity might be generated by mutation in the productively rearrangedTCRGVgenes. As forIGgenes, the mutational target is biased towardGandCbases and (A/G/T)G(C/T)(A/T) motif (orDGYW). The replacement and synonymous substitutions (R/S) ratios inTCRGVregions are higher forCDRthan for framework region, thus suggesting selection toward amino acid changes inCDR. Using the counterpart humanTCRγδ receptor as a template, structural models computed adopting a comparative procedure show that nonconservative mutations contribute to diversity inCDR2 and at the γδVdomain interface.
Redox‐Active Guanidine Ligands with Pyridine and p‐Benzoquinone Backbones
Authors: Stang Simone , Lebkücher Anna , Walter Petra , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: September 2012

Herein we report on the synthesis and some aspects of the chemistry of the new redox‐active ligands 2,3,5,6‐tetrakis(tetramethylguanidino)pyridine, 2,3,5,6‐tetrakis(tetramethylguanidino)‐p‐benzoquinone and 2,3,5,6‐tetrakis(N,N′‐dimethyl‐N,N′‐ethyleneguanidino)‐p‐benzoquinone. All three ligands are strong electron donors. In addition, the p‐benzoquinone systems feature low LUMO energies and small HOMO–LUMO gaps. A comparison of the ligands was made with regard to their optical properties, Brønsted basicity and electron‐donor properties; results of quantum chemical calculations were included in this comparison. Subsequently, dinuclear copper complexes were prepared. Preliminary experiments on their redox chemistry followed.
Functional Hybrid Materials Based on Layered Simple Hydroxide Hosts and Dicarboxylate Schiff Base Metal Complex Guests
Authors: Eyele‐Mezui Séraphin , Delahaye Emilie , Rogez Guillaume , Rabu Pierre
Published: September 2012

The insertion of carboxysalen‐type complexes into magnetic layered transition‐metal simple hydroxides has provided new hybrid compounds. Three kinds of carboxysalen ligands have been used: an ethylenediamine bridge (SED‐H2), a chiral cyclohexanediamine bridge [(S,S)‐SCD‐H2 and (R,R)‐SCD‐H2], and an aromatic o‐phenylenediamine bridge (SBD‐H2). The ccorresponding CuII, NiII, CoII, ZnII, MnIII, and AlIII complexes were synthesized and inserted into layered cobalt and copper hydroxides. The structural and spectroscopic investigations confirmed the successful insertion‐grafting of the complexes leading to new layered hybrid materials in which the inserted complexes act as pillars between the inorganic layers. The use of carboxylate anchoring functions enabled some of the difficulties encountered during the previously reported insertion of sulfonatosalen complex analogues to be overcome, namely hydrolysis and decomplexation during the insertion reaction. Hence, in this work it was possible to insert a wide variety of complexes into layered simple hydroxides, including MIII complexes, for the first time. The insertion of chiral carboxysalen complexes led to the formation of chiral magnets in which chirality transfer to the inorganic layers was evidenced and seems to be favored by the carboxylate anchoring groups. Finally, magnetic characterization showed that the copper hydroxide hybrids exhibit overall antiferrimagnetic behavior, whereas the cobalt hydroxide hybrids present ferromagnetic ordering, with ordering temperatures ranging from 6.5 to 12.8 K. In this case the nature of the cation inserted between the layers influences the magnetic behavior of the hybrid, contrary to what was observed in the case of the sulfonate analogues.
CuI/SnCl2 Co‐Catalyzed Four‐Component Reaction of Ketones, Amines, Alkynes, and Carbon Dioxide
Authors: Zhao Jinwu , Huang Huawen , Qi Chaorong , Jiang Huanfeng
Published: September 2012

The four‐component CuI and SnCl2 co‐catalyzed assembly of ketones, amines, alkynes, and carbon dioxide could be performed in DMSO at 70 °C under CO2 pressure to synthesize 5‐alkynlene oxazolidinones. It was found that steric hindrance had an extreme effect on the four‐component coupling. Aliphatic ketones, basic primary amines, and aryl alkynes were good substrates.
Potassium 4‐Iodylbenzenesulfonate: Preparation, Structure, and Application as a Reagent for Oxidative Iodination of Arenes
Authors: Yusubov Mekhman S. , Yusubova Roza Y. , Nemykin Victor N. , Maskaev Andrey V. , Geraskina Margarita R. , Kirschning Andreas , Zhdankin Viktor V.
Published: September 2012

A new hypervalent iodine(V) compound, potassium 4‐iodylbenzenesulfonate, was prepared by the oxidation of 4‐iodobenzensulfonic acid with Oxone in water. This potassium salt can be further converted into 4‐iodylbenzenesulfonic acid by treatment with the acidic form of Amberlyst 15 in water. A single‐crystal X‐ray structure of potassium 4‐iodylbenzenesulfonate revealed the presence of polymeric chains in the solid state due to a combination of numerous intra‐ and intermolecular interactions. Potassium 4‐iodylbenzenesulfonate will likely find many practical applications as a thermally stable and water‐soluble hypervalent iodine‐based oxidant, particularly useful as a reagent for oxidative iodination of aromatic substrates. This reagent can be effectively recovered from the reaction mixture (92 % recovery) by treatment of the aqueous layer with Oxone at 60 °C for 2 h, followed by filtration of the precipitate.
Evaluation and optimisation of preparative semi‐automated electrophoresis systems for Illumina library preparation
Authors: Quail Michael A. , Gu Yong , Swerdlow Harold , Mayho Matthew
Published: September 2012

Size selection can be a critical step in preparation of next‐generation sequencing libraries. Traditional methods employing gel electrophoresis lack reproducibility, are labour intensive, do not scale well and employ hazardous interchelating dyes. In a high‐throughput setting, solid‐phase reversible immobilisation beads are commonly used for size‐selection, but result in quite a broad fragment size range. We have evaluated and optimised the use of two semi‐automated preparative DNA electrophoresis systems, the Caliper Labchip XT and the Sage Science Pippin Prep, for size selection of Illumina sequencing libraries.
Correlation in spectral accelerations for earthquakes in Europe
Authors: Cimellaro Gian Paolo
Published: September 2012

The shape of a uniform hazard spectrum has been criticized to be unrealistic for a site where the spectral ordinates of the uniform hazard spectrum at different periods are governed by different scenario events and conservative for long‐return‐period earthquake shaking. The conditional mean spectrum considering epsilon (CMS‐ε) takes into account the correlation of spectral demands (represented by values of ε) at different periods, to address these issues. This paper proposes new prediction models for the correlation coefficient of ε(T1) and ε(T2), a key component for developing a CMS, using Pan‐European earthquake records from a European ground motion database. Epsilon (ε) for each record is computed using the 2005 Ambraseys ground‐motion prediction equation. The model can be used to develop CMS for European sites, and it can be incorporated in the European seismic standards. Copyright © 2012 John Wiley & Sons, Ltd.
Parallel fully implicit two‐grid methods for distributed control of unsteady incompressible flows
Authors: Yang Haijian , Cai Xiao‐Chuan
Published: September 2012

In this paper, we investigate some fully coupled parallel two‐grid Lagrange–Newton–Krylov–Schwarz algorithms for the suboptimal distributed control of unsteady incompressible flows governed by the Navier–Stokes equations. The algorithms include two major parts: a two‐grid Newton method for the nonlinear part of the problem and a two‐level Schwarz preconditioner for the linear part of the problem. Most of the existing approaches for distributed control problems are based on the so‐called reduced space method, which is easier to implement, but may have convergence issues in some situations. In the full space approach, we couple the state variables, the control variables, and the adjoint variables in a single large system of nonlinear equations. The coupled system is considerably more ill‐conditioned than its sub‐systems; however, with the powerful two‐grid approach, we are able to solve these difficult systems efficiently on large scale parallel computers. We show numerically that such an approach is scalable in the sense that the number of Newton iterations and the number of linear iterations are both nearly independent of the grid size, the number of processors, and the Reynolds numbers. We present numerical experiments for some suboptimal control problems obtained on supercomputers with more than two thousand processors. Copyright © 2012 John Wiley & Sons, Ltd.
Clay mineralogy as a tool for integrated sequence stratigraphic and palaeogeographic reconstructions: Late Oligocene–Early Aquitanian western internal South Iberian Margin, Spain
Authors: Alcalá F. J. , López‐Galindo A. , Martín‐Martín M.
Published: September 2012

The different hydrodynamic behaviour of detrital clay minerals in the marine depositional environment allows assessment of relative sea‐level variations in the sedimentary record. Comparison of smectite and kaolinite:illite (S+K:I) changes with the global sea‐level curves and with the third‐order cycles of the eustatic curve for European basins allows assessment of the influence of global eustasy and local tectonics on sequence stratigraphy. In the South Iberian Margin, sedimentation took place both on open‐marine platforms and in deeper water areas. On this margin during the Late Oligocene to Early Aquitanian, the variations in sedimentation were caused not only by global eustasy but also by compressive tectonics. Correlations were made between the S+K:I cycles and the third‐order cycles for European basins, enabling the definition of four third‐order sedimentary sequences (here called C1, C2, C3, and A1) and two lower‐order sequences within C3 and A1 (here called C3a, C3b, A1a, and A1b) related to tectonic movements. High S+K:I values were observed during episodes of maximum flooding in each sequence and lower‐order sequence and in each succession, enabling changes in palaeocoastal morphology to be considered. Copyright © 2012 John Wiley & Sons, Ltd.
Depressive symptoms and frailty
Authors: St. John Philip D. , Tyas Suzanne L. , Montgomery Patrick R.
Published: September 2012

Background

Frailty and depressive symptoms are common issues facing older adults and may be associated.

Objectives

To determine if: (i) depressive symptoms are associated with frailty; (ii) there is a gradient in this effect across the range of depressive symptoms; and (iii) the association between depressive symptoms and frailty is specific to particular types of depressive symptoms (positive affect, negative affect, somatic complaints, and interpersonal relations).

Method

Secondary analysis of an existing population‐based study was conducted.

Population

In 1991, 1751 community‐living adults aged 65+ years were interviewed.

Measures

Depressive symptoms were measured using the Center for Epidemiologic Studies—Depression (CES‐D) scale. Frailty was graded from 0 (no frailty) to 3 (moderate/severe frailty). Age, gender, education, marital status, self‐rated health, and the number of comorbid conditions were self‐reported.

Analyses

Logistic regression models were constructed with the outcome of no frailty/urinary incontinence only versus frailty.

Results

Depressive symptoms were strongly associated with frailty, and there was a gradient effect across the entire range of the CES‐D scale. The odds ratio and 95% confidence interval was 1.08 (1.06, 1.09) per point of the CES‐D in unadjusted models. After potential confounding factors were adjusted, the adjusted odds ratio (95% confidence interval) was 1.03 (1.01, 1.05). Positive affect, negative affect, and somatic complaints were all associated with frailty, whereas interpersonal relations were not associated with frailty.

Conclusions

Depressive symptoms are associated with frailty. Clinicians should consider assessing frail older adults for the presence of depression. Copyright © 2012 John Wiley & Sons, Ltd.
Multisystem physiological dysfunction is associated with depressive symptoms in a population‐based sample of older adults
Authors: Kobrosly Roni W. , Seplaki Christopher L. , Cory‐Slechta Deborah A. , Moynihan Jan , van Wijngaarden Edwin
Published: September 2012

Objective

To evaluate the association between multisystem physiological dysfunction and depressive symptom severity in the US older adults.

Methods

We examined 2405 adults of age 60 years and older by using the data from the 2005–2008 National Health and Nutrition Examination Survey. We constructed a summary score of “physiological dysfunction,” encompassing cardiovascular function, glucose regulation, liver function, and renal function. Overall depressive symptoms were obtained from the 9‐item Patient Health Questionnaire depression scale, and factor analysis was used to derive affective and somatic symptom scores. We employed multiple linear regression models to estimate associations between physiological dysfunction scores and affective, somatic, and overall depressive symptoms, while adjusting for demographic, socioeconomic factors, and other potentially confounding factors.

Results

Greater multisystem physiological dysfunction scores were associated with an increased severity of overall, affective, and somatic depressive symptoms. These associations persisted after adjusting for all covariates: beta = 0.23 (95% confidence interval (CI) = 0.13, 0.32); beta = 0.08 (95% CI = 0.04, 0.11); beta = 0.12 (95% CI = 0.06, 0.18), respectively.

Conclusions

Our results suggest that the multisystem physiological dysfunction is associated with late‐life depressive symptoms. Additional longitudinal studies of links between allostatic load, psychosocial stress events throughout the life course, and late‐life depressive symptoms may shed further light on this association. Copyright © 2012 John Wiley & Sons, Ltd.
Roles of hepatocyte and myeloid CXC chemokine receptor-2 in liver recovery and regeneration after ischemia/reperfusion in mice
Authors: Van Sweringen Heather L. , Sakai Nozomu , Quillin Ralph C. , Bailey Jeff , Schuster Rebecca , Blanchard John , Goetzman Holly , Caldwell Charles C. , Edwards Michael J. , Lentsch Alex B.
Published: September 2012

Previous studies have demonstrated the significance of signaling through the CXC chemokine receptor-2 (CXCR2) receptor in the process of recovery and regeneration of functional liver mass after hepatic ischemia/reperfusion (I/R). CXCR2 is constitutively expressed on both neutrophils and hepatocytes; however, the cell-specific roles of this receptor are unknown. In the present study, chimeric mice were created through bone marrow transplantation (BMT) using wild-type and CXCR2-knockout mice, yielding selective expression of CXCR2 on hepatocytes (Hep) and/or myeloid cells (My) in the following combinations: Hep+/My+; Hep−/My+; Hep+/My−; and Hep−/My−. These tools allowed us to assess the contributions of myeloid and hepatocyte CXCR2 in the recovery of the liver after I/R injury. Flow cytometry confirmed the adoption of the donor phenotype in neutrophils. Interestingly, Kupffer cells from all chimeras lacked CXCR2 expression. Recovery/regeneration of hepatic parenchyma was assessed by histologic assessment and measurement of hepatocyte proliferation. CXCR2Hep+/My+ mice showed the least amount of liver recovery and hepatocyte proliferation, whereas CXCR2Hep−/My− mice had the greatest liver recovery and hepatocyte proliferation. CXCR2Hep+/My− mice had enhanced liver recovery, with hepatocyte proliferation similar to CXCR2Hep−/My− mice. Myeloid expression of CXCR2 directly regulated CXC chemokine expression levels after hepatic I/R, such that mice lacking myeloid CXCR2 had markedly increased chemokine expression, compared with mice expressing CXCR2 on myeloid cells. Conclusion: The data suggest that CXCR2 on myeloid cells is the predominant regulator of liver recovery and regeneration after I/R injury, whereas hepatocyte CXCR2 plays a minor, secondary role. These findings suggest that myeloid cell-directed therapy may significantly affect liver regeneration after liver resection or transplantation. (Hepatology 2013)
Quantifying the Fraction of Cirrhosis Attributable to Alcohol Among Chronic Hepatitis C Virus Patients: Implications for Treatment Cost-Effectiveness
Authors: Innes Hamish A. , Hutchinson Sharon J. , Barclay Stephen , Cadzow Elaine , Dillon John F. , Fraser Andrew , Goldberg David J. , Mills Peter R. , McDonald Scott A. , Morris Judith , Stanley Adrian , Hayes Peter
Published: September 2012

A substantial baseline risk of liver cirrhosis exists for patients with chronic hepatitis C virus (HCV) infection. However, the extent to which this could be driven by heavy alcohol use is unclear. Therefore, our principal aim was to determine the fraction of cirrhosis attributable to heavy alcohol use among chronic HCV patients attending a liver clinic. The study population comprised chronic HCV patients who had attended one of five liver clinics in Scotland during 1996-2010 and had (1) remained in follow-up for at least 6 months, (2) acquired HCV through either injecting drugs or blood transfusion, and (3) an estimated date of acquiring infection. Predictors of cirrhosis were determined from multivariate logistic regression. Regression parameters were used to determine the fraction of cirrhosis attributable to heavy alcohol use. Among 1,620 patients, 9% were diagnosed with cirrhosis, and 34% had ever engaged in heavy alcohol use (>50 units/week for a sustained period). Significant predictors of cirrhosis were age, duration of infection, and ever heavy alcohol use. The fraction of cirrhosis attributable to ever heavy alcohol use was 36.1% (95% confidence interval [CI]: 24.4-47.4). Moreover, among patients who had ever engaged in heavy alcohol use specifically, this attributable fraction exceeded 50% (61.6%; 95% CI: 47.0-72.2).

Conclusions:

A substantial proportion of patients with chronic HCV develop liver cirrhosis as a consequence of heavy alcohol use. This has not been adequately acknowledged by cost utility analyses (CUAs). As such, estimates of cost-effectiveness may be exaggerated. Thus, these data are important to guide forthcoming CUAs in terms of taking better account of the factors leading to cirrhosis among patients with chronic HCV.
A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice
Authors: Puche Juan E. , Lee Youngmin A. , Jiao Jingjing , Aloman Costica , Fiel Maria I. , Muñoz Ursula , Kraus Thomas , Lee Tingfang , Yee Hal F. , Friedman Scott L.
Published: September 2012

We have developed a novel model for depleting mouse hepatic stellate cells (HSCs) that has allowed us to clarify their contributions to hepatic injury and fibrosis. Transgenic (Tg) mice expressing the herpes simplex virus thymidine kinase gene (HSV-Tk) driven by the mouse GFAP promoter were used to render proliferating HSCs susceptible to killing in response to ganciclovir (GCV). Effects of GCV were explored in primary HSCs and in vivo. Panlobular damage was provoked to maximize HSC depletion by combining CCl4 (centrilobular injury) with allyl alcohol (AA) (periportal injury), as well as in a bile duct ligation (BDL) model. Cell depletion in situ was quantified using dual immunofluorescence (IF) for desmin and GFAP. In primary HSCs isolated from both untreated wild-type (WT) and Tg mice, GCV induced cell death in ˜50% of HSCs from Tg, but not WT, mice. In TG mice treated with CCl4+AA+GCV, there was a significant decrease in GFAP and desmin-positive cells, compared to WT mice (˜65% reduction; P < 0.01), which was accompanied by a decrease in the expression of HSC-activation markers (alpha smooth muscle actin, beta platelet-derived growth factor receptor, and collagen I). Similar results were observed after BDL. Associated with HSC depletion in both fibrosis models, there was marked attenuation of fibrosis and liver injury, as indicated by Sirius Red/Fast Green, hematoxylin and eosin quantification, and serum alanine/aspartate aminotransferase. Hepatic expression of interleukin-10 and interferon-gamma was increased after HSC depletion. No toxicity of GCV in either WT or Tg mice accounted for the differences in injury. Conclusion: Activated HSCs significantly amplify the response to liver injury, further expanding this cell type's repertoire in orchestrating hepatic injury and repair. (Hepatology 2013)
Intrahepatic Cholestasis of Pregnancy Levels of Sulfated Progesterone Metabolites Inhibit Farnesoid X Receptor Resulting in a Cholestatic Phenotype
Authors: Abu-Hayyeh Shadi , Papacleovoulou Georgia , Lövgren-Sandblom Anita , Tahir Mehreen , Oduwole Olayiwola , Jamaludin Nurul Akmal , Ravat Sabiha , Nikolova Vanya , Chambers Jenny , Selden Clare , Rees Myrddin , Marschall Hanns-Ulrich , Parker Malcolm G. , Williamson Catherine
Published: September 2012

Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death. The endocrine signals that cause cholestasis are not known but 3α-sulfated progesterone metabolites have been shown to be elevated in ICP, leading us to study the impact of sulfated progesterone metabolites on farnesoid X receptor (FXR)-mediated bile acid homeostasis pathways. Here we report that the 3β-sulfated progesterone metabolite epiallopregnanolone sulfate is supraphysiologically raised in the serum of ICP patients. Mice challenged with cholic acid developed hypercholanemia and a hepatic gene expression profile indicative of FXR activation. However, coadministration of epiallopregnanolone sulfate with cholic acid exacerbated the hypercholanemia and resulted in aberrant gene expression profiles for hepatic bile acid-responsive genes consistent with cholestasis. We demonstrate that levels of epiallopregnanolone sulfate found in ICP can function as a partial agonist for FXR, resulting in the aberrant expression of bile acid homeostasis genes in hepatoma cell lines and primary human hepatocytes. Furthermore, epiallopregnanolone sulfate inhibition of FXR results in reduced FXR-mediated bile acid efflux and secreted FGF19. Using cofactor recruitment assays, we show that epiallopregnanolone sulfate competitively inhibits bile acid-mediated recruitment of cofactor motifs to the FXR-ligand binding domain.

Conclusion:

Our results reveal a novel molecular interaction between ICP-associated levels of the 3β-sulfated progesterone metabolite epiallopregnanolone sulfate and FXR that couples the endocrine component of pregnancy in ICP to abnormal bile acid homeostasis.
Reduced Hepatic Stellate Cell Expression of Kruppel-Like Factor 6 Tumor Suppressor Isoforms Amplifies Fibrosis During Acute and Chronic Rodent Liver Injury
Authors: Ghiassi-Nejad Zahra , Hernandez-Gea Virginia , Woodrell Christopher , Lang Ursula E. , Dumic Katja , Kwong Allison , Friedman Scott L.
Published: September 2012

Kruppel-like factor 6 (KLF6), a zinc finger transcription factor and tumor suppressor, is induced as an immediate-early gene during hepatic stellate cell (HSC) activation. The paradoxical induction of a tumor suppressor in HSCs during proliferation led us to explore the biology of wildtype KLF6 (KLF6WT) and its antagonistic, alternatively spliced isoform KLF6SV1 in cultured HSCs and animal models. The animal models generated include a global heterozygous KLF6 mouse (

Klf6+/−

), and transgenic mice expressing either

hKLF6

WT

or

hKLF6

SV1

under the control of the

Collagen α2 (I)

promoter to drive HSC-specific gene expression following injury. The rat

Klf6

transcript has multiple splice forms that are homologous to those of the human

KLF6

gene. Following a transient increase, all rat

Klf6

isoforms decreased in response to acute carbon tetrachloride (CCl4) liver injury and culture-induced activation. After acute CCl4,

Klf6+/−

mice developed significantly increased fibrosis and enhanced fibrogenic messenger RNA (mRNA) and protein expression. In contrast, HSC-specific transgenic mice overexpressing

KLF6WT

or

KLF6

SV1

developed significantly diminished fibrosis with reduced expression of fibrogenic genes. Chromatin IP and quantitative reverse-transcription polymerase chain reaction in mouse HSCs overexpressing

KLF6

WT

demonstrated KLF6WT binding to GC boxes in promoters of

Colα1 (I), Colα2 (I),

and beta-platelet-derived growth factor receptor (β-
Pdgfr

) with reduced gene expression, consistent with transcriptional repression by KLF6. Stellate cells overexpressing either

KLF6WT

or

KLF6

SV1

were more susceptible to apoptotic stress based on poly (ADP-ribose) polymerase (PARP) cleavage.

Conclusion:

KLF6 reduces fibrogenic activity of HSCs by way of two distinct mechanisms, direct transcriptional repression of target fibrogenic genes and increased apoptosis of activated HSCs. These results suggest that following its initial induction, sustained down-regulation of KLF6 in liver injury may allow de-repression of fibrogenic genes and decreased stellate cell clearance by inhibiting apoptosis.
Information Problems and Company Behaviour vis‐à‐vis Continuous Management Training
Authors: Barrutia Jon , Landeta Jon , Araujo Andrés , Hoyos Jon
Published: September 2012

The purpose of this study is to examine the degree and type of information the company holds on training, and to what extent the lack‐of‐information firms suffer in two senses, information on managerial resources and information on training supply, tends to condition their behavior vis‐à‐vis management training. Data from more than 300 Spanish companies with 50 or more workers are used to examine the connection between information asymmetries and company behavior in relation to continuous management training. The empirical study revealed that company readiness to engage in continuous management training appears to be significantly conditioned by all variables related to the existence of information on managers and training supply. Based on these results, underinvestment in managerial training would be associated with those cases in which information is unavailable or not distributed uniformly and transparently. This study contributes to the existing training literature by providing a novel link between information asymmetries (firm managers; firm training offerings) and their ability to influence training investment rates. © 2012 Wiley Periodicals, Inc.
Beryllium‐7: The Cinderella of fallout radionuclide sediment tracers?
Authors: Walling D. E.
Published: September 2012

Current concern for the sustainable management of soil resources and the many adverse effects of increased sediment loads on streams and river systems has generated a need for more information on rates and patterns of soil loss and an improved understanding of catchment sediment budgets. Traditional measurement techniques are frequently unable to meet the requirements and fallout radionuclides have been shown to offer considerable potential for tracing the mobilization, transfer, redistribution and storage of soil and sediment within catchments and river systems. Caesium‐137 and lead‐210 have been the most widely used fallout radionuclide sediment tracers, but their half‐lives mean that the information that they provide is in most instances limited to the medium term (e.g. 25–120 years). The need for information on shorter timescales has directed attention to the potential for using beryllium‐7, which has a considerable shorter half‐life, for tracing soil and sediment redistribution over short timescales (e.g. days–weeks). To date, however, there have been relatively few attempts to exploit this potential. This situation is likely to be in part a reflection of the emphasis of early work on 137Cs and 210Pb and the more recent nature of work using 7Be. However, it may also reflect the limitations and constraints imposed by the nature of 7Be fallout and the short half‐life of this radionuclide. This contribution explores recent work in using 7Be as a sediment tracer and the constraints imposed by its origin and behaviour. Attention is directed to fallout inputs, the application of 7Be to tracing soil and sediment redistribution on slopes and on river floodplains, its use as a source fingerprint and other related applications. The likely future potential of 7Be as a sediment tracer is assessed. Copyright © 2012 John Wiley & Sons, Ltd.
Hydraulic model evaluation for large‐scale flood risk assessments
Authors: Falter Daniela , Vorogushyn Sergiy , Lhomme Julien , Apel Heiko , Gouldby Ben , Merz Bruno
Published: September 2012

For a nationwide flood risk assessment in Germany, simulations of inundation depth and extent for all major catchments are required. Therefore, a fast two‐dimensional (2D) hydraulic model is needed. From the range of existing methods, two storage cell models are evaluated to find an appropriate method for large‐scale applications. The Dynamic Rapid Flood Spreading Model (Dynamic RFSM) based on irregular storage cells, and a raster‐based model with inertia formulation of momentum equation are compared. Simulation performed with the fully dynamic shallow water model InfoWorks RS 2D served as a reference. The hydraulic models are applied to a test area having a very flat topography adjacent to the river Elbe. As a benchmark scenario, the outflow through a hypothetical dike breach was chosen. To investigate the impact of the grid resolution on run time and model performance, the simulation with the raster model is carried out with different grid sizes. Furthermore, the sensitivity of the Dynamic RFSM to the choice of time step was analysed. Both models were able to simulate the final inundation extent and depths with a reasonable accuracy. However, the Dynamic RFSM showed some weakness in simulating inundation extent over the flat test area. Coarsening the grid resolution reduced the run time of the raster‐based model considerably and can be regarded as a promising strategy to constrain the computational efforts for a large‐scale application, although the model accuracy gradually deteriorated. With similar run time, the raster‐based model performed better than the Dynamic RFSM in terms of inundation extent and comparable regarding maximum inundation depth. Generally, an application at national scale appears feasible with both hydraulic modelling schemes. Copyright © 2012 John Wiley & Sons, Ltd.
Influence of Temporal Distance on the Perceived Importance of Career‐Related Self‐Efficacy and Outcome Expectations
Authors: Lee Seungcheol Austin , Park Hee Sun
Published: September 2012

Because all career choices are about future actions, time is an important contextual variable in social cognitive career choice (Hesketh, 2000). However, there is a dearth of research examining the effect of time. The authors examined how temporal distance to career entry influences the perceived importance of self‐efficacy and outcome expectations concerning a career pursuit. They also examined the moderating effects of perceived support and barriers, as well as country. The participants were college students in the United States (n= 180) and in South Korea (n= 215). The results of hierarchical regression analyses did not show main effects of time, but a 3‐way interaction indicated the complex interplay of time and other contextual variables. Implications for career counseling and future research are discussed.
Improving Prediction of Significant Career‐Related Constructs for High School Students With Learning Disabilities
Authors: Dipeolu Abiola O. , Hargrave Stephanie , Sniatecki Jessica L. , Donaldson Joseph
Published: September 2012

Preparing students with learning disabilities (LDs) to make the transition into the world of work is considered an essential preparation that high schools can provide. However, existing services are limited for career development preparation, and available programs rely on assessments normed for samples of students without LDs. This study examined the predictability of critical career‐related constructs of dysfunctional career thoughts, career maturity, and vocational identity in high school students with LDs, using a sample of 139 such students. Data analyses were performed using multiple regression and t tests. Results indicate that it is possible to predict important career constructs for students with LDs using standardized instruments, which can inform subsequent interventions.
Coming Full Circle: Reoccurring Career Development Trends in Schools
Authors: Schenck Paulette M. , Anctil Tina M. , Smith Carol Klose , Dahir Carol
Published: September 2012

Current state and national mandates focusing on academic achievement have drawn critical counseling resources away from career development. As the world of work radically changes and economic situations remain uncertain, the call for a return to school counseling roots based in career guidance has never been louder. The authors explore reoccurring career guidance trends throughout the history of school counseling to expand awareness of the basis of today's career and technical education discussions and increase understanding of the interconnectedness of career guidance and counseling and educational reform.
DNA damage kinetics and apoptosis in ivermectin‐treated chinese hamster ovary cells
Authors: Molinari Gabriela , Kujawski Maciej , Scuto Anna , Soloneski Sonia , Larramendy Marcelo L.
Published: September 2012

A comet assay was used to analyze DNA damage kinetics in Chinese hamster ovary (CHO‐K1) cells induced by antiparasitic ivermectin (IVM) and the IVM‐containing technical formulation Ivomec® (IVO; 1% IVM). Cells were treated with 50 µg ml–1 IVM and IVO for 80 min, washed and re‐incubated in antiparasiticide‐free medium for 0–24 h until assayed using the single‐cell gel electrophoresis assay (SCGE). Cell viability remained unchanged up to 3 h of incubation. After 6 h of treatment, cell survival decreased up to 75% and 79% in IVM‐ and IVO‐treated cultures, respectively, remaining unchanged within 12–24 h after treatment. For both anthelmintics, biphasic behavior in DNA damage occurred during the incubation time. A time‐dependent increase of IVM‐ and IVO‐induced DNA damage was observed within 0 to 3 h after pulse treatment, revealed by a progressive decrease of undamaged cells and an increase in slightly damaged and damaged cells. Finally, a time‐dependent decrease in IVM‐ and IVO‐induced DNA damage was revealed by a progressive decrease of slightly damaged cells and the absence of damaged cells simultaneously with an increase in the frequency of undamaged cells during the final 18 h of incubation. Flow cytometry analysis revealed that both compounds are able to induce a marked increase in early and late apoptosis. Based on our observations, we could conclude that the decrease in DNA lesions is mostly related to IVM‐induced cytotoxicity rather than attributable to a repair process. Copyright © 2012 John Wiley & Sons, Ltd.
A quantitative bioapatite/collagen calibration method using Raman spectroscopy of bone
Authors: Karampas I. A. , Orkoula M. G. , Kontoyannis C. G.
Published: September 2012

Numerous calibration models were developed and tested for the quantitative analysis of collagen and bioapatite in bone using Raman spectroscopy. The ν1 phosphate vibration at 960 cm–1 was used as indicator of the content of bioapatite while for collagen three markers were used: the C–H2 band at 2940 cm–1, the amide I band at 1667 cm–1 and the vibrations of proline and hydroxyproline at 855 and 878 cm–1, respectively. Also a calibration model based on the PLS algorithm was developed, too. Validation of the derived calibration models indicated that the model that makes use of the height ratio of the peaks 960/(855+878) exhibits the best accuracy. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Evaluation of zebrafish brain development using optical coherence tomography
Authors: Lin Yu‐Sheng , Chu Chin‐Chou , Tsui Po‐Hsiang , Chang Chien‐Cheng
Published: September 2012

The zebrafish is a well‐established model system used to study and understand various human biological processes. The present study used OCT to investigate growth of the adult zebrafish brain. Twenty zebrafish were studied, using their standard lengths as indicators of their age. Zebrafish brain aging was evaluated by analyzing signal attenuation rates and texture features in regions of interest (ROIs). Optical scattering originates from light interaction with biological structures. During development, the zebrafish brain gains cells. Signal attenuation rate, therefore, increases with increasing zebrafish brain age. This study's analyses of texture features could not identify aging in zebrafish brain. These results, therefore, indicated that the OCT signal attenuation rate can indicate zebrafish brain aging, and its analysis provides a more effective means of observing zebrafish brain aging than texture features analysis. Using OCT system could further increase the technique's potential for recognition and monitoring of zebrafish brain development (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Microarray analysis of Drosophila dicer‐2 mutants reveals potential regulation of mitochondrial metabolism by endogenous siRNAs
Authors: Lim Do‐Hwan , Lee Langho , Oh Chun‐Taek , Kim Nam‐Hoon , Hwang Seungwoo , Han Sung‐Jun , Lee Young Sik
Published: September 2012

RNA interference is a eukaryotic regulatory mechanism by which small non‐coding RNAs typically mediate specific silencing of their cognate genes. In Drosophila, the RNase III enzyme Dicer‐2 (Dcr‐2) is essential for biogenesis of endogenous small interfering RNAs (endo‐siRNAs), which have been implicated in regulation of endogenous protein‐coding genes. Although much is known about microRNA‐based regulatory networks, the biological functions of endo‐siRNAs in animals remain poorly understood. We performed gene expression profiling on Drosophila dcr‐2 null mutant pupae to investigate transcriptional effects caused by a severe defect in endo‐siRNA production, and found 306 up‐regulated and 357 down‐regulated genes with at least a twofold change in expression compared with the wild type. Most of these up‐regulated and down‐regulated genes were associated with energy metabolism and development, respectively. Importantly, mRNA sequences of 39% of the up‐regulated genes were perfectly complementary to the sequences of previously reported endo‐siRNAs, suggesting they may be direct targets of endo‐siRNAs. We confirmed up‐regulation of five selected genes matching endo‐siRNAs and concomitant down‐regulation of the corresponding endo‐siRNAs in dcr‐2 mutant pupae. Most of the potential endo‐siRNA target genes were associated with energy metabolism, including the citric acid cycle and oxidative phosphorylation in mitochondria, implying that these are major metabolic processes directly affected by endo‐siRNAs in Drosophila. Consistent with this finding, dcr‐2 null mutant pupae had lower ATP content compared with controls, indicating that mitochondrial energy production is impaired in these mutants. Our data support a potential role for the endo‐siRNA pathway in energy homeostasis through regulation of mitochondrial metabolism. J. Cell. Biochem. 114: 418–427, 2013. © 2012 Wiley Periodicals, Inc.
Imaging the efficacy of UVC irradiation on superficial brain tumors and metastasis in live mice at the subcellular level
Authors: Momiyama Masashi , Suetsugu Atsushi , Kimura Hiroaki , Kishimoto Hiroyuki , Aki Ryoichi , Yamada Akimitsu , Sakurada Harumi , Chishima Takashi , Bouvet Michael , Endo Itaru , Hoffman Robert M.
Published: September 2012

The effect of UVC irradiation was investigated on a model of brain cancer and a model of experimental brain metastasis. For the brain cancer model, brain cancer cells were injected stereotactically into the brain. For the brain metastasis model, lung cancer cells were injected intra‐carotidally or stereotactically. The U87 human glioma cell line was used for the brain cancer model, and the Lewis lung carcinoma (LLC) was used for the experimental brain metastasis model. Both cancer cell types were labeled with GFP in the nucleus and RFP in the cytoplasm. A craniotomy open window was used to image single cancer cells in the brain. This double labeling of the cancer cells with GFP and RFP enabled apoptosis of single cells to be imaged at the subcellular level through the craniotomy open window. UVC irradiation, beamed through the craniotomy open window, induced apoptosis in the cancer cells. UVC irradiation was effective on LLC and significantly extended survival of the mice with experimental brain metastasis. In contrast, the U87 glioma was relatively resistant to UVC irradiation. The results of this study suggest the use of UVC for treatment of superficial brain cancer or metastasis. J. Cell. Biochem. 114: 428–434, 2013. © 2012 Wiley Periodicals, Inc.
MicroRNA‐mediated somatic cell reprogramming
Authors: Kuo Chih‐Hao , Ying Shao‐Yao
Published: September 2012

Since the first report of induced pluripotent stem cells (iPSCs) using somatic cell nuclear transfer (SCNT), much focus has been placed on iPSCs due to their great therapeutic potential for diseases such as abnormal development, degenerative disorders, and even cancers. Subsequently, Takahashi and Yamanaka took a novel approach by using four defined transcription factors to generate iPSCs in mice and human fibroblast cells. Scientists have since been trying to refine or develop better approaches to reprogramming, either by using different combinations of transcription factors or delivery methods. However, recent reports showed that the microRNA expression pattern plays a crucial role in somatic cell reprogramming and ectopic introduction of embryonic stem cell‐specific microRNAs revert cells back to an ESC‐like state, although, the exact mechanism underlying this effect remains unclear. This review describes recent work that has focused on microRNA‐mediated approaches to somatic cell reprogramming as well as some of the pros and cons to these approaches and a possible mechanism of action. Based on the pivotal role of microRNAs in embryogenesis and somatic cell reprogramming, studies in this area must continue in order to gain a better understanding of the role of microRNAs in stem cells regulation and activity. J. Cell. Biochem. 114: 275–281, 2013. © 2012 Wiley Periodicals, Inc.
Reactive oxygen species‐induced activation of ERK and p38 MAPK mediates PMA‐induced NETs release from human neutrophils
Authors: Keshari Ravi S. , Verma Anupam , Barthwal Manoj K. , Dikshit Madhu
Published: September 2012

Neutrophils/polymorphonuclear leukocytes (PMNs), an important component of innate immune system, release extracellular traps (NETs) to eliminate invaded pathogens; however understanding of the role of signaling molecules/proteins need to be elucidated. In the present study role of p38 MAPK and extracellular signal regulated kinase (ERK) against phorbol 12‐myristate 13‐acetate (PMA) induced reactive oxygen species (ROS) generation and NETs formation has been investigated. Human neutrophils were treated with PMA to induce free radical generation and NETs release, which were monitored by NBT reduction and elastase/DNA release, respectively. PMA treatment led to the time dependent phosphorylation of p38 MAPK and ERK in PMNs. Pretreatment of PMNs with SB202190 or U0126 did not significantly reduce PMA induce free radical generation, but prevented NETs release. Pretreatment of PMNs with NADPH oxidase inhibitor (diphenyleneiodonium chloride) significantly reduced free radical generation, p38 MAPK and ERK phosphorylation as well as NETs release, suggesting that p38 MAPK and ERK activation was downstream to free radical generation. The present study thus demonstrates ROS dependent activation of ERK and p38 MAPK, which mediated PMA induced NETs release from human neutrophils. J. Cell. Biochem. 114: 532–540, 2013. © 2012 Wiley Periodicals, Inc.
Hepatitis C virus core protein stimulates fibrogenesis in hepatic stellate cells involving the obese receptor
Authors: Wu Ching‐Fen , Lin Yun‐Lian , Huang Yi‐Tsau
Published: September 2012

Hepatitis C virus core protein (HCVcp), which is secreted by infected cells, is reported as an immunomodulator in immune cells. However, the effects of HCVcp on hepatic stellate cells (HSCs), the key cells in liver fibrosis, still remain unclear. In this study, we investigated the effects of HCVcp on obese receptor (ObR) related downstream signaling pathways and fibrogenic gene expression in HSCs. LX‐2, a human HSC line, was incubated with HCVcp. Inhibitors and short interfering RNAs were used to interrogate the mechanisms of HCVcp action on HSCs. HCVcp (20–100 ng/ml) concentration‐dependently stimulated α‐smooth muscle actin (α‐SMA) protein expression and mRNA expression of α‐SMA, procollagen α2(I) and TGF‐β1 genes, with a plateau of 220% of controls at 100 ng/ml. HCVcp induced mRNA and protein expression of ObR. Blocking of Ob‐Rb with a neutralizing antibody inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and AMPKα stimulated by HCVcp. Furthermore, knockdown of Ob‐Rb down‐regulated HCVcp‐induced STAT3, AKT, and AMPKα phosphorylation, and reversed HCVcp‐suppressed mRNA expression of matrix metalloproteinase (MMP)‐1, peroxisome proliferator‐activated receptor (PPAR)γ and sterol regulatory element binding protein‐1c (SREBP‐1c) genes. AMPKα signaling blockade reversed HCVcp‐suppressed SREBP‐1c mRNA expression. HCVcp stimulated reactive oxygen species formation and gp91phox (a component of NADPH oxidase) protein expression, together with AKT phosphorylation, leading to suppression of PPARγ and SREBP‐1c genes. Our results provide a new finding that HCVcp induced ObR‐dependent Janus Kinase (JAK) 2–STAT3, AMPKα, and AKT signaling pathways and modulated downstream fibrogenetic gene expression in HSCs. J. Cell. Biochem. 114: 541–550, 2013. © 2012 Wiley Periodicals, Inc.
An efficient algorithm for complete active space valence bond self‐consistent field calculation
Authors: Song Jinshuai , Chen Zhenhua , Shaik Sason , Wu Wei
Published: September 2012

This article describes a novel algorithm for the optimization of valence bond self‐consistent field (VBSCF) wave function for a complete active space (CAS), so‐called VBSCF(CAS). This was achieved by applying the strategies adopted in the optimization of CASSCF wave functions to VBSCF(CAS) wave functions, using an auxiliary orthogonal orbital set that generates the same configuration space as the original nonorthogonal orbital set. Theoretical analyses and test calculations show that the VBSCF(CAS) method shares the same computational scaling as CASSCF. The test calculations show the current capability of VBSCF method, which involves millions of VB structures. © 2012 Wiley Periodicals, Inc.