bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel inflammatory biomarkers of portal pressure in compensated cirrhosis patients
Authors: Buck Martina , Garcia-Tsao Guadalupe , Groszmann Roberto J. , Stalling Caitlin , Grace Norman D. , Burroughs Andrew K. , Patch David , Matloff Daniel S. , Clopton Paul , Chojkier Mario
Published: October 2013

The rationale for screening inflammatory serum biomarkers of the hepatic vein pressure gradient (HVPG) is based on the fact that portal hypertension is pathogenically related to liver injury and fibrosis, and that in turn these are associated with the activation of inflammatory pathways. This was a nested cohort study in the setting of a randomized, clinical trial to assess the development of gastroesophageal varices (GEV) (N Engl J Med 2005;353:2254). Patients had cirrhosis and portal hypertension but did not have GEV. A total of 90 patients who had baseline day-1 sera available were enrolled in the present study. The objective of this study was to determine whether inflammatory biomarkers in conjunction with clinical parameters could be used to develop a predictive paradigm for HVPG. The correlations between HVPG and interleukin (IL)-1β (P = 0.0052); IL-1R-α (P = 0.0085); Fas-R (P = 0.0354), and serum VCAM-1 (P = 0.0007) were highly significant. By using multivariate logistic regression analysis and selected parameters (transforming growth factor beta [TGFβ]; heat shock protein [HSP]-70; at-risk alcohol use; and Child class B) we could exclude HVPG ≥12 mmHg with 86% accuracy (95% confidence interval [CI]: 67.78 to 96.16%) and the sensitivity was 87.01% (95% CI: 69.68 to 96.34%). Therefore, the composite test could identify 86% of compensated cirrhosis patients with HVPG below 12 mmHg and prevent unnecessary esophagogastroduodenoscopy with its associated morbidity and costs in these patients. Our diagnostic test was not efficient in predicting HVPG ≥12 mmHg. Conclusion: A blood test for HVPG could be performed in cirrhosis patients to prevent unnecessary esophagogastroduodenoscopy. (HEPATOLOGY 2014;59:1052–1059)
MKKing the most of liver regeneration: An in vivo screen identifies the MKK4 pathway as a suppressor of regeneration
Authors: Jacob Vinitha , Sadler Kirsten C. , Wuestefeld T , Pesic M , Rudalska R , Dauchm D , Longerich T , Kang T W
Published: October 2013

Abstract

The liver harbors a distinct capacity for endogenous regeneration; however, liver regeneration is often impaired in disease and therefore insufficient to compensate for the loss of hepatocytes and organ function. Here we describe a functional genetic approach for the identification of gene targets that can be exploited to increase the regenerative capacity of hepatocytes. Pools of small hairpin RNAs (shRNAs) were directly and stably delivered into mouse livers to screen for genes modulating liver regeneration. Our studies identify the dual-specific kinase MKK4 as a master regulator of liver regeneration. MKK4 silencing robustly increased the regenerative capacity of hepatocytes in mouse models of liver regeneration and acute and chronic liver failure. Mechanistically, induction of MKK7 and a JNK1-dependent activation of the AP1 transcription factor ATF2 and the Ets factor ELK1 are crucial for increased regeneration of hepatocytes with MKK4 silencing.
Novel Death Defying Domain in Met Entraps the Active Site of Caspase-3 and Blocks Apoptosis in Hepatocytes
Authors: Ma Jihong , Zou Chunbin , Guo Lida , Seneviratne Danushka S. , Tan Xinping , Kwon Yong-Kook , An Jiyan , Bowser Robert , DeFrances Marie C. , Zarnegar Reza
Published: October 2013

Met, the transmembrane tyrosine kinase receptor for hepatocyte growth factor (HGF), is known to function as a potent antiapoptotic mediator in normal and neoplastic cells. Herein we report that the intracellular cytoplasmic tail of Met has evolved to harbor a tandem pair of caspase-3 cleavage sites, which bait, trap, and disable the active site of caspase-3, thereby blocking the execution of apoptosis. We call this caspase-3 cleavage motif the Death Defying Domain (DDD). This site consists of the following sequence: DNAD-DEVD-T (where the hyphens denote caspase cleavage sites). Through functional and mechanistic studies, we show that upon DDD cleavage by caspase-3 the resulting DEVD-T peptide acts as a competitive inhibitor and entraps the active site of caspase-3 akin to DEVD-CHO, which is a potent, synthetic inhibitor of caspase-3 activity. By gain- and loss-of-function studies using restoration of DDD expression in DDD-deficient hepatocytic cells, we found that both caspase-3 sites in DDD are necessary for inhibition of caspase-3 and promotion of cell survival. Employing mutagenesis studies, we show that DDD could operate independently of Met's enzymatic activity as determined by using kinase-dead human Met mutant constructs. Studies of both human liver cancer tissues and cell lines uncovered that DDD cleavage and entrapment of caspase-3 by DDD occur

in vivo

, further proving that this site has physiological and pathophysiological relevance.

Conclusion :

Met can directly inhibit caspase-3 by way of a novel mechanism and promote hepatocyte survival. The results presented here will further our understanding of the mechanisms that control not only normal tissue homeostasis but also abnormal tissue growth such as cancer and degenerative diseases in which apoptotic caspases are at play. (Hepatology 2014;59:2010–2021)
Diagnostic accuracy of 18F-methylcholine positron emission tomography/computed tomography for intra- and extrahepatic hepatocellular carcinoma
Authors: Bieze Matthanja , Klümpen Heinz-Josef , Verheij Joanne , Beuers Ulrich , Phoa Saffire S.K.S. , van Gulik Thomas M. , Bennink Roelof J.
Published: October 2013

Diagnosis of hepatocellular carcinoma (HCC) primarily involves imaging. The aim of this study was to assess the accuracy of 18F-fluorocholine (18F-FCH) positron emission tomography (PET) for detection of HCC and evaluation of extent of disease. Patients with HCC >1 cm were included between 2009 and July 2011, and follow-up closed in February 2013. Diagnosis was based on American Association for the Study of Liver Diseases criteria, and all patients underwent 18F-FCH PET/computed tomography (CT) at baseline before treatment, 6 underwent a second PET/CT posttreatment, and 1 a third during follow-up. Whole-body PET and low-dose CT imaging were performed 15 minutes after 18F-FCH injection. Evaluation of imaging was done with standardized uptake value (SUV) ratios: SUV maximum of the lesion divided by the SUV mean of surrounding tissue. Statistical analyses included descriptive analyses, receiver operating characteristic curve, McNemar's test, and Kaplan-Meier's test at 5% level of significance. Twenty-nine patients revealed 53 intrahepatic lesions. In 48 of 53 lesions, 18F-FCH PET was positive (SUVratio, 1.95 ± 0.66; sensitivity, 88%; specificity, 100%). PET/CT showed uptake in 18 extrahepatic lesions and no uptake in 3 lesions affirmed non-HCC lesions; all lesions were confirmed with additional investigation (accuracy, 100%). In 17 of 29 patients, additional lesions were found on PET/CT imaging, with implications for treatment in 15 patients. Posttreatment PET/CT showed identical results, compared with standard treatment evaluation. Conclusion: This study shows additional value of 18F-FCH PET/CT for patients with HCC. 18F-FCH PET/CT has implications for staging, management, and treatment evaluation because of accurate assessment of extrahepatic disease. (HEPATOLOGY 2014;59:996–1006)
Soret Effect on Darcy–Brinkman Convection in a Binary Viscoelastic Fluid‐Saturated Porous Layer
Authors: Gaikwad S.N. , Dhanraj M.
Published: October 2013

A linear and weakly nonlinear stability analyses is performed to study the onset of Darcy–Brinkman double diffusive convection in a binary viscoelastic fluid‐saturated porous layer in the presence of the Soret effect. The modified Darcy–Brinkman–Oldroyd model including the time derivative term is employed for the momentum equation. The expressions for stationary, oscillatory, and finite amplitude Rayleigh number are obtained as a function of the governing parameters. There is a competition between the processes of the Soret coefficient, viscoelasticity, thermal diffusion, and solute diffusion that causes the convection to set in through an oscillatory mode rather than a stationary mode. The effects of the Soret parameter, Darcy number, relaxation and retardation parameters, and Darcy–Prandtl number on the stationary, oscillatory, and finite amplitude convection is shown graphically. The weakly nonlinear theory is based on truncated representation of the Fourier series method and is used to find the Nusselt and Sherwood numbers. Further, the transient behavior of the Nusselt and Sherwood numbers is investigated by solving the nonlinear system of ordinary differential equations numerically using the Runge–Kutta method. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(4): 297–320, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21076
MHD Boundary Layer Flow of a Nanofluid Over an Exponentially Stretching Sheet in the Presence of Radiation
Authors: Loganathan P. , Vimala C.
Published: October 2013

Effects of thermal radiation on the steady laminar magnetohydrodynamic boundary layer flow of a nanofluid over an exponentially stretching sheet is studied theoretically. The governing boundary layer equations of the problem are formulated and transformed into ordinary differential equations, using a similarity transformation. The resulting ordinary differential equations are solved numerically by the shooting method. The effects of the parameters, namely, the magnetic parameter M, radiation parameter NR, and the solid volume fraction parameter ϕ, are discussed and presented in detail. Different types of nanoparticles namely, Cu, Ag, Al2O3, and TiO2 with the base fluid water, are studied. It is found that the nanoparticles with low thermal conductivity, TiO2 have better enhancement on heat transfer, compared to Cu, Ag, and Al2O3. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(4): 321–331, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21077
Constrained Optimization of Heat Transfer from an Extended Surface
Authors: Thyageswaran Sridhar
Published: October 2013

Two different zero‐order optimization techniques are used to maximize the rates of heat transfer from a fin assembly of a specified cost and in the shape of several annular fins that are mounted on a central stem. The problem is formulated to account for two‐dimensional steady‐state heat transfer that is limited by several inequality constraints. The dimensionless governing equations are used to identify the relevant decision variables. The number of fins making up the assembly is treated as an input parameter. A digital computer is used to determine the required temperature distributions and to implement the optimization search algorithms. Three different fin materials are assessed—aluminum, copper and carbon steel. Design optimizations of the extended surface assembly were made over a range of operating conditions, encompassing several different convection heat transfer coefficients that are representative of free and forced convection in air, and several different overall temperature differences between the substrate surface and air. A few recommendations based on trends in the predicted results are given. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(6): 504–521, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21093
Cytochrome P450 2A13 mediates the neoplastic transformation of human bronchial epithelial cells at a low concentration of aflatoxin B1
Authors: Zhang Zhan , Lu Huiyuan , Huan Fei , Meghan Cromie , Yang Xuejiao , Wang Yun , Wang Xichen , Wang Xinru , Wang Shou‐Lin
Published: October 2013

Cytochrome P450 2A13 (CYP2A13), mainly expressed in human respiratory tract, is highly efficient in the metabolic activation of aflatoxin (AF) B1 (AFB1) and is assumed to play a role in human lung tumorigenesis in airborne AFB1 exposure. To validate the assumption, we exposed human bronchial epithelial (BEAS‐2B) cells stably expressing CYP2A13 (B‐2A13), CYP1A2 (B‐1A2) and CYP2A6 (B‐2A6) to 0.1–10 nM AFB1 for 30–50 passages. B‐2A13 cells showed increased sensitivity to 0.1 nM AFB1‐induced neoplastic transformation and the formation of tumors in nude mice were observed at passage 30 (P30) while it occurred at P50 B‐1A2 cells. B‐2A6, similar to vector control, showed no neoplastic transformation in this condition. Additionally, AFB1‐DNA adducts and 8‐OHdG significantly increased in transformed P40 B‐2A13, in parallel with the upregulation of p‐ATR, p‐BRCA1, Mre11, Rad50 and Rad51. However, the apoptosis of P40 cells was near normal, while the expression of Bax, C‐Caspase 3 and C‐PARP increased passage‐dependently. Inhibition of ATR (ATR siRNA or NU6027) reversely increased the apoptosis of P40 B‐2A13 cells in parallel with the upregulation of Bax, C‐Caspase 3 and C‐PARP, suggesting that ATR plays an important role in maintaining cell survival via antiapoptosis. Additionally, activation of ATR was necessary to neoplastic transformation since blockage of ATR in P40 cells inhibited DNA damage repair response and anchorage‐independent growth. Our data demonstrated that CYP2A13 played a critical role in AFB1‐induced neoplastic transformation. ATR‐mediated the dysfunction of apoptosis and DNA damage repair might be involved. These results help establish a linkage between airborne AFB1 and human respiratory carcinoma.
Influence of omega‐3 fatty acids on Tamoxifen‐induced suppression of rat mammary carcinogenesis
Authors: Manni Andrea , Richie John P. , Xu Haifang , Washington Sharlene , Aliaga Cesar , Bruggeman Richard , Cooper Timothy K. , Prokopczyk Bogdan , Trushin Neil , Calcagnotto Ana , Das Arunangshu , Liao Jason , El‐Bayoumy Karam
Published: October 2013

We report here a detailed time course study of the individual and combined chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on multiple histologic parameters of mammary carcinogenesis. Groups of female Sprague‐Dawley rats were injected ip with 1‐methyl‐1‐nitrosourea at 50 days of age and assigned to either a control diet (20% corn oil [CO]) or a FO‐rich diet (10% FO + 10% CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when ∼90% of control rats had palpable tumors). Our results demonstrate a major effect of Tam in inhibiting the development of early preneoplastic lesions. FO, while having a marginal protective effect of it own, enhanced the antitumor action of Tam on all histologic parameters of carcinogenesis, although the effects of the combination were not statistically different from those of Tam alone. The combination of FO and Tam was the only intervention that induced regression of established preneoplastic lesions. We also found that in contrast to plasma, only target tissue n‐3 fatty acids (FAs) levels correlated with select tissue biomarkers of carcinogenesis whose expression was altered in a manner predictive of a protective effect. Our results demonstrating the potentially superior chemopreventive efficacy of Tam and n‐3FA have important translational implications. Our data also emphasize the importance of local factors in affecting target tissue levels and biologic effects of n‐3FA.
Rethinking Academic Literacies
Authors: Kiili Carita , Mäkinen Marita , Coiro Julie
Published: October 2013

This manuscript introduces a multidimensional framework for academic literacies to help instructors become more aware of different aspects of literacies and how they might be used to plan and orchestrate meaningful, multifaceted literacy experiences in their classes. More specifically, this broad framework for literacy and learning explicitly considers the overlapping role of argumentation, digital inquiry, collaboration, and innovation as they are applied to continuously evolving disciplinary literacy practices. The framework is applied to a course designed for pre‐service teachers that integrated several aspects of academic literacies and offered some pedagogical guidelines to support their literacy development. A summary of the different domains of academic literacies and research‐based pedagogical guidelines is provided to assist teachers in various disciplines and educational levels in applying the framework in their own instructional contexts.
Using quantitative structure–activity relationship modeling to quantitatively predict the developmental toxicity of halogenated azole compounds
Authors: Craig Evisabel A. , Wang Nina Ching , Zhao Q. Jay
Published: October 2013

Developmental toxicity is a relevant endpoint for the comprehensive assessment of human health risk from chemical exposure. However, animal developmental toxicity data remain unavailable for many environmental contaminants due to the complexity and cost of these types of analyses. Here we describe an approach that uses quantitative structure–activity relationship modeling as an alternative methodology to fill data gaps in the developmental toxicity profile of certain halogenated compounds. Chemical information was obtained and curated using the OECD Quantitative Structure–Activity Relationship Toolbox, version 3.0. Data from 35 curated compounds were analyzed via linear regression to build the predictive model, which has an R2 of 0.79 and a Q2 of 0.77. The applicability domain (AD) was defined by chemical category and structural similarity. Seven halogenated chemicals that fit the AD but are not part of the training set were employed for external validation purposes. Our model predicted lowest observed adverse effect level values with a maximal threefold deviation from the observed experimental values for all chemicals that fit the AD. The good predictability of our model suggests that this method may be applicable to the analysis of qualifying compounds whenever developmental toxicity information is lacking or incomplete for risk assessment considerations. Copyright © 2013 John Wiley & Sons, Ltd.
Decreased Quantity and Quality of the Periarticular and Nonperiarticular Bone in Patients With Rheumatoid Arthritis: A Cross-Sectional HR-pQCT Study
Authors: Kocijan Roland , Finzel Stephanie , Englbrecht Matthias , Engelke Klaus , Rech Jürgen , Schett Georg
Published: October 2013

Rheumatoid arthritis (RA) is a highly bone destructive disease. Although it is well established that RA leads to bone loss and increased fracture risk, current knowledge on the microstructural changes of bone in RA is still limited. The purpose of this study was to assess the microstructure of periarticular and nonperiarticular bone in female and male RA patients and compare it with respective healthy controls. We performed two high-resolution peripheral quantitative computed tomography (HR-pQCT; Xtreme-CT) scans, one of the distal radius and one of the ultradistal radius in 90 patients with RA (60 females, 30 males) and 70 healthy controls (40 females, 30 males) matched for sex, age, and body mass index. Volumetric bone mineral density (vBMD), bone geometry, and bone microstructure including trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical thickness (Ct.Th) and cortical porosity (Ct.Po) were assessed. At the distal and ultradistal radius, trabecular (p = 0.005 and p < 0.001) and cortical BMD (p < 0.001 and p < 0.001) were significantly decreased in male and female patients with RA, respectively. BV/TV was also decreased at both sites, based on lower Tb.N in female RA (p < 0.001 for both sites) and lower Tb.Th (p = 0.034 and p = 0.005) in male RA patients compared with respective healthy controls. Cortical thinning (p = 0.018 and p = 0.002) but not Ct.Po (p = 0.070 and p = 0.275) was pronounced in male and female RA patients at the distal radius. Cortical perimeter was increased in male and female RA patients at both sites. Multiple regression models showed that bone geometry (cortical perimeter) is predominantly influenced by age of the RA patient, cortical thickness by both age and disease duration, and trabecular microstructure predominantly by the disease duration. In summary, these data show profound deterioration of bone microstructure in the appendicular skeleton of RA patients at both periarticular and nonperiarticular sites. © 2014 American Society for Bone and Mineral Research.
Comparison of the capillary wave method and pressure tensor route for calculation of interfacial tension in molecular dynamics simulations
Authors: Nickerson Stella , Frost Denzil S. , Phelan Harrison , Dai Lenore L.
Published: October 2013

We have studied the calculation of surface and interfacial tension for a variety of liquid–vapor and liquid–liquid interfaces using molecular dynamics (MD) simulations. Because of the inherently small scale of MD systems, large pressure fluctuations can cause imprecise calculations of surface tension using the pressure tensor route. The capillary wave method exhibited improved precision and stability throughout all of the simulated systems in this study. In order to implement this method, the interface was defined by fitting an error function to the density profile. However, full mapping of the interface from coordinate files produced enhanced accuracy. Upon increasing the system size, both methods exhibited higher precision, although the capillary wave method was still more reliable. © 2013 Wiley Periodicals, Inc.
Highly asymmetric electrolytes in the primitive model: Hypernetted chain solution in arbitrary spatial dimensions
Authors: Heinen Marco , Allahyarov Elshad , Löwen Hartmut
Published: October 2013

The pair‐correlation functions for fluid ionic mixtures in arbitrary spatial dimensions are computed in hypernetted chain (HNC) approximation. In the primitive model (PM), all ions are approximated as nonoverlapping hyperspheres with Coulomb interactions. Our spectral HNC solver is based on a Fourier‐Bessel transform introduced by Talman (J. Comput. Phys. 1978, 29, 35), with logarithmically spaced computational grids. Numeric efficiency for arbitrary spatial dimensions is a commonly exploited virtue of this transform method. Here, we highlight another advantage of logarithmic grids, consisting in efficient sampling of pair‐correlation functions for highly asymmetric ionic mixtures. For three‐dimensional fluids, ion size and charge‐ratios larger than 1000 can be treated, corresponding to hitherto computationally not accessed micrometer‐sized colloidal spheres in 1‐1 electrolyte. Effective colloidal charge numbers are extracted from our PM results. For moderately large ion size and charge‐asymmetries, we present molecular dynamics simulation results that agree well with the approximate HNC pair correlations. © 2013 Wiley Periodicals, Inc.
RNA Polymerase II CTD Modifications: How Many Tales From a Single Tail
Authors: Napolitano Giuliana , Lania Luigi , Majello Barbara
Published: October 2013

Eukaryote's RNA polymerases II (RNAPII) have the feature to contain, at the carbossi‐terminal region of their largest subunit Rpb1, a unique CTD domain. Rpb1‐CTD is composed of an increasing number of repetitions of the Y1S2P3T4S5P6S7 heptad that goes in parallel with the developmental level of organisms. Because of its composition, the CTD domain has a huge structural plasticity; virtually all the residues can be subjected to post‐translational modifications and the two prolines can either be in cis or trans conformations. In light of these features, it is reasonable to think that different specific nuances of CTD modification and interacting factors take place not only on different gene promoters but also during different stages of the transcription cycle and reasonably might have a role even if the polymerase is on or off the DNA template. Rpb1‐CTD domain is involved not only in regulating transcriptional rates, but also in all co‐transcriptional processes, such as pre‐mRNA processing, splicing, cleavage, and export. Moreover, recent studies highlight a role of CTD in DNA replication and in maintenance of genomic stability and specific CTD‐modifications have been related to different CTD functions. In this paper, we examine results from the most recent CTD‐related literature and give an overview of the general function of Rpb1‐CTD in transcription, transcription‐related and non transcription‐related processes in which it has been recently shown to be involved in. J. Cell. Physiol. 229: 538–544, 2014. © 2013 Wiley Periodicals, Inc.
Steady‐state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit
Authors: Cheatham S. Christian , Fleming Megan R. , Healy Daniel P. , Chung Eun Kyoung , Shea Katherine M. , Humphrey Melissa L. , Kays Michael B.
Published: October 2013

The study objective was to evaluate meropenem pharmacokinetics and pharmacodynamics in morbid obesity. Nine patients hospitalized in an intensive care unit with a body mass index ≥40 kg/m2 received meropenem 500 mg or 1 g q6h, infused over 0.5 hours. Pharmacokinetic parameters were estimated, and Monte Carlo simulations were performed for 5 dosing regimens (500 mg q8h, 1 g q8h, 2 g q8h, 500 mg q6h, 1 g q6h) infused over 0.5 and 3 hours. Probability of target attainment (PTA) was calculated using fT > MIC of 40% and 54%. Total body weight and body mass index were 152.3 ± 31.0 kg and 54.7 ± 8.6 kg/m2, respectively. Volume of distribution of the central compartment was 13.3 ± 6.7 L, volume of distribution at steady‐state was 37.4 ± 14.7 L, and systemic clearance was 10.2 ± 5.0 L/h. At an MIC of 2 µg/mL, PTA was ≥90% for 4/5 and 2/5 regimens infused over 0.5 hours and for 5/5 and 4/5 regimens infused over 3 hours at 40% and 54% fT > MIC, respectively. Standard doses achieve adequate exposures for susceptible bacteria at a pharmacodynamic target of 40% fT > MIC. Higher doses or prolonged infusion regimens are needed at the higher pharmacodynamic target.
Netupitant PET imaging and ADME studies in humans
Authors: Spinelli Tulla , Calcagnile Selma , Giuliano Claudio , Rossi Giorgia , Lanzarotti Corinna , Mair Stuart , Stevens Lloyd , Nisbet Ian
Published: October 2013

Netupitant is a new, selective NK1 receptor antagonist under development for the prevention of chemotherapy‐induced nausea and vomiting. Two studies were conducted to evaluate the brain receptor occupancy (RO) and disposition (ADME) of netupitant in humans. Positron emission tomography (PET) imaging with the NK1 receptor‐binding–selective tracer [11C]‐GR205171 was used to evaluate the brain penetration of different doses of netupitant (100, 300, and 450 mg) and to determine the NK1‐RO duration. A NK1‐RO of 90% or higher was achieved with all doses in the majority of the tested brain regions at Cmax, with a long duration of RO. The netupitant minimal plasma concentration predicted to achieve a NK1‐RO of 90%, C90%, in the striatum was 225 ng/mL; after administration of netupitant 300 mg, concentrations exceeded the C90%. In the ADME study, a single nominal dose of [14C]‐netupitant 300 mg was used to assess its disposition. Absorption was rapid and netupitant was extensively metabolized via Phase I and II hepatic metabolism. Elimination of >90% was predicted at day 29 and was principally via hepatic/biliary route (>85%) with a minor contribution of the renal route (<5%). In conclusion, these studies demonstrate that netupitant is a potent agent targeting NK1 receptors with long lasting RO. In addition, netupitant is extensively metabolized and is mainly eliminated through the hepatic/biliary route and to a lesser extent via the kidneys.
Plasmon‐induced reduction of bromate with Au–Ag–AgI/Al2O3 under visible‐light irradiation
Authors: Peng Tianwei , Tu Jinjun , Hu Chun , Hu Xuexiang , Zhou Xuefeng
Published: October 2013

BACKGROUND

The plasmon‐induced photocatalytic reduction of bromate (BrO3–) was investigated in visible‐light irradiated Au–Ag–AgI/Al2O3 suspension. The BrO3– reduction process was studied in detail.

RESULTS

The catalyst was found to be highly effective for the reduction of BrO3– from pH 3 to 6. An enhancement of the electrical interaction between BrO3– and the positively charged surface of the photocatalyst favored adsorption and reduction of BrO3–. Organic compounds such as ethanol could react as sacrificial electron donors with excited holes (h+) on the metal nanoparticles (NPs) to accelerate electron transfer, inhibiting the release of metal ions and the recombination of h+ and electrons, hence promoting photocatalytic reduction of BrO3–. Electron quenching and cyclic voltammetry studies under a variety of experimental conditions verified that BrO3– trapped conduction band electrons of AgI from the excited metal NPs were reduced, competing with O2.

CONCLUSION

The photocatalyst Au–Ag–AgI/Al2O3 exhibited particularly good reduction of BrO3– under visible‐light irradiation. The BrO3– reduction was highly favored at acidic condition due to the greater adsorption of BrO3– onto the catalyst. This finding indicates that this visible‐light‐driven catalyst could be applied to the reduction of some oxidative pollutants or even simultaneous removal of both oxidative and reductive pollutants. © 2013 Society of Chemical Industry
Combined effects of food deprivation and food frequency on the amount and temporal distribution of schedule‐induced drinking
Authors: Castilla José Luis , Pellón Ricardo
Published: October 2013

Under intermittent food schedules animals develop temporally organized behaviors throughout interfood intervals, with behaviors early in the intervals (interim) normally occurring in excess. Schedule‐induced drinking (a prototype of interim, adjunctive behavior) is related to food deprivation and food frequency. This study investigated the interactions that resulted from combining different food‐deprivation levels (70%, 80% or 90% free‐feeding weights) with different food‐occurrence frequencies (15‐, 30‐ or 60‐s interfood intervals) in a within‐subjects design. Increases in food deprivation and food frequency generally led to increased licking, with greater differences due to food deprivation as interfood intervals became shorter. Distributions of licking were modestly shifted to later in the interfood interval as interfood intervals lengthened, a result that was most marked under 90% food deprivation, which also resulted in flatter distributions. It would therefore appear that food deprivation modulates the licking rate and the distribution of licking in different ways. Effects of food deprivation and food frequency are adequately explained by a theory of adjunctive behavior based on delayed food reinforcement, in contrast to alternative hypotheses.
The effect of the Madden‐Julian Oscillation on station rainfall and river level in the Fly River system, Papua New Guinea
Authors: Matthews Adrian J. , Pickup Geoff , Peatman Simon C. , Clews Peter , Martin Jason
Published: October 2013

The Madden‐Julian oscillation (MJO) is the dominant mode of intraseasonal variability in tropical rainfall on the large scale, but its signal is often obscured in individual station data, where effects are most directly felt at the local level. The Fly River system, Papua New Guinea, is one of the wettest regions on Earth and is at the heart of the MJO envelope. A 16 year time series of daily precipitation at 15 stations along the river system exhibits strong MJO modulation in rainfall. At each station, the difference in rainfall rate between active and suppressed MJO conditions is typically 40% of the station mean. The spread of rainfall between individual MJO events was small enough such that the rainfall distributions between wet and dry phases of the MJO were clearly separated at the catchment level. This implies that successful prediction of the large‐scale MJO envelope will have a practical use for forecasting local rainfall. In the steep topography of the New Guinea Highlands, the mean and MJO signal in station precipitation is twice that in the satellite Tropical Rainfall Measuring Mission 3B42HQ product, emphasizing the need for ground‐truthing satellite‐based precipitation measurements. A clear MJO signal is also present in the river level, which peaks simultaneously with MJO precipitation input in its upper reaches but lags the precipitation by approximately 18 days on the flood plains.
The effect of 1.9 and 1.4 Ga impact events on 4.3 Ga zircon and phosphate from an Apollo 15 melt breccia
Authors: Grange M. L. , Nemchin A. A. , Pidgeon R. T.
Published: October 2013

Zircon and phosphate grains from matrix and quartz‐monzodiorite (QMD) clasts in two thin sections of Apollo 15 impact melt breccia 15405 were investigated using optical microscopy, scanning electron microscopy, Raman spectroscopy, and ion microprobe U‐Pb analyses. U‐Pb results for zircon grains with well‐defined cathodoluminescence zoning define the primary (i.e., magmatic) crystallization age as 4330 ± 6 Ma (2σ). One zircon consists of a preserved inner part surrounded by a porous polycrystalline (“granular”) mixture of zircon and baddeleyite, indicating incomplete reaction of the zircon with melt. Previous work showed that this microstructure could form at pressures above 60 GPa and a temperature close to ~1700°C and is evidence of an impact‐related melting event. The U‐Pb system of this grain indicates a resetting event at 1940 ± 10 Ma, interpreted as the age of this impact (impact #1). Other zircon and phosphate grains also have disturbed U‐Pb systems, showing an even younger reset event (impact #2) at 1407 ± 57 Ma. Evidence of impact is supported by microstructures of zircon and baddeleyite such as secondary rims. These impacts are tentatively identified as those having formed Autolycus and Aristillius craters.
A Facile Method for the Synthesis of Hydrazine‐4‐oxothiazolidine and Imino‐5‐oxothiadiazine Derivatives from 1,4‐Disubstituted Thiosemicarbazides
Authors: Hassan Alaa A. , Aly Ashraf A. , Bedair Tarek I. M. , Brown Alan B. , El‐Emary Talaat I.
Published: October 2013

1,4‐Disubstituted thiosemicarbazides reacted with dimethyl acetylenedicarboxylate with formation of (2‐hydrazono‐4‐oxothiazolidin‐5‐ylidene)acetates and, in one case, a (2‐imino‐1,3,4‐thiadiazin‐5‐on‐6‐ylidene)acetate. Several mechanistic options involving nucleophilic interaction are presented. The structures of all newly synthesized compounds were identified by 1H NMR, 13C NMR, COSY, HMQC and HMBC spectral data.
R2* as a surrogate measure of ferriscan iron quantification in thalassemia
Authors: Chan Wesley C. , Tejani Zahra , Budhani Faisal , Massey Christine , Haider Masoom A.
Published: October 2013

Purpose

To determine whether R2* values are a consistent predictor of hepatic iron concentration (HIC) in thalassemia patients by demonstrating a correlation between R2* relaxation rates and FerriScan‐determined HIC.

Materials and Methods

Eighty‐eight patients with thalassemia major were retrospectively evaluated. All patients underwent FerriScan imaging and multiecho gradient echo imaging. The results from FerriScan analysis were fitted against R2* estimates using linear regression.

Results

There was a very strong linear correlation between R2* values and FerriScan‐determined HIC (Spearman correlation of 0.976; 95% confidence interval [CI]: 0.963, 0.984).

Conclusion

R2* values can predict HIC determined by FerriScan using a linear calibration curve. This technique may provide a potentially cost‐saving alternative for hepatic iron determination and improve acceptance by referring physicians. J. Magn. Reson. Imaging 2014;39:1007–1011. © 2013 Wiley Periodicals, Inc.
Physiorack: An integrated MRI safe/conditional, Gas delivery, respiratory gating, and subject monitoring solution for structural and functional assessments of pulmonary function
Authors: Halaweish Ahmed F. , Charles H. Cecil
Published: October 2013

Purpose

To evaluate the use of a modular MRI conditional respiratory monitoring and gating solution, designed to facilitate proper monitoring of subjects' vital signals and their respiratory efforts, during free‐breathing and breathheld 19F, oxygen‐enhanced, and Fourier‐decomposition MRI‐based acquisitions.

Materials and Methods

All Imaging was performed on a Siemens TIM Trio 3 Tesla MRI scanner, following Institutional Review Board approval. Gas delivery is accomplished through the use of an MR compatible pneumotachometer, in conjunction with two three‐way pneumatically controlled Hans Rudolph Valves. The pneumatic valves are connected to Douglas bags used as the gas source. A mouthpiece (+nose clip) or an oro‐nasal Hans Rudolph disposable mask is connected following the pneumatic valve to minimize dead‐space and provide an airtight seal. Continuous monitoring/sampling of inspiratory and expiratory oxygen and carbon dioxide levels at the mouthpiece/mask is achieved through the use of an Oxigraf gas analyzer.

Results

Forty‐four imaging sessions were successfully monitored, during Fourier‐decomposition (n = 3), fluorine‐enhanced (n = 29), oxygen‐enhanced, and ultra short echo (n = 12) acquisitions. The collected waveforms, facilitated proper monitoring and coaching of the subjects.

Conclusion

We demonstrate an inexpensive, off‐the‐shelf solution for monitoring these signals, facilitating assessments of lung function. Monitoring of respiratory efforts and exhaled gas concentrations assists in understanding the heterogeneity of lung function visualized by gas imaging. J. Magn. Reson. Imaging 2014;39:735–741. © 2013 Wiley Periodicals, Inc.
Influenza C virus infection in military recruits—symptoms and clinical manifestation
Authors: Kauppila Jaana , Rönkkö Esa , Juvonen Raija , Saukkoriipi Annika , Saikku Pekka , Bloigu Aini , Vainio Olli , Ziegler Thedi
Published: October 2013

Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus infections are poorly characterized. Respiratory infections in military recruits in eastern Finland were monitored between July 2004 and December 2005 in order to study the epidemiology and clinical picture of infections caused by this virus. Blood samples were obtained at entry and at the end of the military service, and during each episode of respiratory infection to measure antibody responses against 10 viral and 2 bacterial pathogens. If possible, sputum samples were collected during the acute phase of respiratory infection episodes. Symptoms of the episodes were recorded for comparison of the clinical picture caused by various infectious agents. Infection with influenza C virus was detected in 38 of 892 young men during their service. The virus usually caused a mild upper respiratory tract infection. Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness. A striking difference to infections caused by influenza A virus was the lack of fever. Influenza C virus is an important cause of a respiratory tract infection in army conscripts. Infections with this virus are usually mild but can be complicated in some cases. J. Med. Virol. 86:879–885, 2014. © 2013 Wiley Periodicals, Inc.
Clinical evaluation of a bioluminescent enzyme immunoassay for detecting norovirus in fecal specimens from patients with acute gastroenteritis
Authors: Shigemoto Naoki , Tanizawa Yukie , Matsuo Takeshi , Sakamaki Nozomi , Ohiro Yoshiyuki , Takayasu Susumu , Fukuda Shinji
Published: October 2013

Noroviruses (NoVs), which belong to the family Caliciviridae, are major causative agents of acute gastroenteritis worldwide. Thus, rapid and highly sensitive assays for detecting NoVs are required. Recently, a bioluminescent enzyme immunoassay (BLEIA) for detecting NoVs in fecal specimens was developed. This new assay was evaluated using fecal specimens obtained from acute gastroenteritis patients. Of the 107 specimens that were found to be NoV‐positive by RT‐PCR or RT‐LAMP, 104 specimens produced positive results in the BLEIA (sensitivity: 96.3%). On the other hand, no false‐positive results were observed during the testing of 176 NoV‐negative specimens containing group A or C rotaviruses, astroviruses, sapoviruses, adenovirus type 41, bocaviruses, or parechoviruses. Furthermore, the BLEIA was able to detect many NoV genotypes in the tested specimens, including three genotypes from genogroup I (genotypes 1, 4, and 8) and ten genotypes belonging to genogroup II (genotypes 1, 2, 3, 4, 5, 6, 12, 13, 16, and 19). By quantifying the number of NoV genome copies in the clinical specimens tested with the BLEIA, its detection limit was estimated to be 106 genome copies per gram of stool and below. Furthermore, as the BLEIA can be performed with an automated device and does not involve complicated procedures it can be used to rapidly test many samples. Therefore, the BLEIA is a rapid and highly sensitive method and could be used as a diagnostic tool at hospitals and clinical laboratories that deal with large numbers of clinical specimens from acute gastroenteritis patients or food handlers. J. Med. Virol. 86:1219–1225, 2014. © 2013 Wiley Periodicals, Inc.
Molecular characterization of norovirus variants and genetic diversity of noroviruses and sapoviruses in Thailand
Authors: Chaimongkol Natthawan , Khamrin Pattara , Malasao Rungnapa , Thongprachum Aksara , Kongsricharoern Tipachan , Ukarapol Nuthapong , Ushijima Hiroshi , Maneekarn Niwat
Published: October 2013

Norovirus (NoV) and Sapovirus (SaV) have been reported as a common cause of acute gastroenteritis worldwide. For a decade, surveillances of NoV and SaV have been conducted continually in Thailand. To monitor the epidemiological situation and to determine the genetic variation of NoV and SaV in Chiang Mai, Thailand, 567 samples collected from pediatric patients hospitalized with acute gastroenteritis were examined during 2007, and 2010–2011 by semi‐nested RT‐PCR and nucleotide sequencing methods. NoV was detected at 15.9%. Phylogenetic analysis revealed multiple NoV genotypes, GI/14 (1.1%), GII/1 (1.1%), GII/2 (1.1%), GII/3 (4.4%), GII/4 (65.6%), GII/6 (10.0%), GII/7 (2.2%), GII/12 (4.4%), GII/13 (3.3%), GII/16 (5.7%), and unclassified genotype (1.1%), circulating in this area. Among these, NoV GII/4 was the most prevalent genotype with a predominance of GII/4 2009 over other variants, 1996, 2006a, and 2006b. For SaV, the prevalence was 1.2% which was much lower than those of NoV and only SaV GI/1 was detected. This study highlights the epidemiology of NoV and SaV and genetic diversity of viruses circulating in pediatric patients hospitalized with acute gastroenteritis in Chiang Mai, Thailand.J. Med. Virol. 86:1210–1218, 2014.© 2013 Wiley Periodicals, Inc.
Analysis of the RF and noise performance of junctionless MOSFETs using Monte Carlo simulation
Authors: Chen Yongbo , Xu Ruimin
Published: October 2013

The dynamic characteristics and high‐frequency noise performance of junctionless (JL) metal‐oxide‐semiconductor field‐effect transistors (MOSFETs) are investigated using a full‐band Monte Carlo simulator. A detailed comparison with conventional inversion mode (IM) MOSFETs is presented. The results of the radio frequency performance indicate that, compared with the traditional IM MOSFET, the JL transistor exhibits lower drain current (Ids), transconductance (gm), and cut‐off frequency (ft) because of its lower electron velocity in the high doping channel. However, owing to a reduced output conductance (gds) and a larger Cgs/Cgd ratio (Cgs is the gate‐to‐source capacitance; Cgd is the gate‐to‐drain capacitance), the JL MOSFET presents an improvement in the intrinsic voltage gain (Avo) and maximum frequency of oscillation (fmax) in comparison with the IM transistor, which makes it be a viable option for the high‐voltage and power gain analog/radio frequency applications. The results of the noise characteristics show that the JL MOSFET exhibits higher minimum noise figure (NFmin) and equivalent noise resistance (Rn), indicating an inferior noise performance. Copyright © 2013 John Wiley & Sons, Ltd.
Diverse nodule bacteria were associated with Astragalus species in arid region of northwestern China
Authors: Chen Weimin , Sun Liangliang , Lu Jianjun , Bi Liangliang , Wang Entao , Wei Gehong
Published: October 2013

The legume species of Astragalus as traditional Chinese medicine source and environmental protection plants showed an extensive distribution in the arid region of northwestern China. However, few rhizobia associating with Astragalus have been investigated in this region so far. In this study, 78 endophytic bacteria were isolated from root nodules of 12 Astragalus species and characterized by the PCR‐RFLP of 16S rRNA gene and symbiotic genes together with the phylogenetic analysis. Results showed that the majority (53%) of isolates are non‐nodulating Agrobacterium sp. and the rest are Mesorhizobium genomic species (41%), Ensifer spp. and Rhizobium gallicum (6%), respectively. Mesorhizobium genomic species are broadly distributed in the Astragalus symbioses and most of them share similar symbiotic genes. It seems that horizontal gene transfer occurred frequently among different genomic species independent of their original hosts and sites. Astragalus adsurgens is nodulated by a widely range of rhizobial species in the nodulation test, revealing that it could play an important role in diversification of Astragalus symbionts and that might be a reason for its wide adaptation to diverse environments.
Generation of regional climate ensembles using Atmospheric Forcing Shifting
Authors: Sasse Romi , Schädler Gerd
Published: October 2013

Ensembles of high‐resolution regional climate model (RCM) simulations are crucial for assessing regional climate change and the associated uncertainties. This article presents an RCM ensemble generation technique which explores uncertainties arising from the positioning of synoptic systems in the large‐scale atmospheric forcing by shifting the atmospheric fields from global climate model (GCM) runs horizontally. Here, we discuss how the so‐called Atmospheric Forcing Shifting (AFS) affects temperature and precipitation over Europe for the period 1980–1984. We use ERA‐40 reanalysis data in which the atmospheric fields are shifted to each direction by 25 and 50 km, respectively, to run RCM simulations with COSMO‐CLM at 50‐km resolution. The analysis of the AFS ensemble includes comparisons with E‐OBS observations and COSMO‐CLM runs driven by different GCMs. AFS has an evident effect on the spatiotemporal distributions of temperature and particularly precipitation, which is most pronounced during hydrological summer (May to October) when spatial weather patterns are more variable. Furthermore, AFS produces realistic changes in the likelihood and intensity of extreme precipitation. The changes induced by AFS depend strongly on orography, i.e. precipitation increases are likely to occur where moist air masses are shifted towards the windward mountain side and vice versa. Thus, increasing the RCM ensemble spread by means of AFS is a simple and useful method for sampling observed climate statistics and assessing the variability and changes in mean and extreme climate.