bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer
Authors: Kluth Martina , Harasimowicz Silvia , Burkhardt Lia , Grupp Katharina , Krohn Antje , Prien Kristina , Gjoni Jovisa , Haß Thomas , Galal Rami , Graefen Markus , Haese Alexander , Simon Ronald , Hühne‐Simon Julia , Koop Christina , Korbel Jan , Weischenfeld Joachim , Huland Hartwig , Sauter Guido , Quaas Alexander , Wilczak Waldemar , Tsourlakis Maria‐Christina , Minner Sarah , Schlomm Thorsten
Published: February 2014

Despite a multitude of p53 immunohistochemistry (IHC) studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. A tissue microarray including 11,152 prostate cancer samples was analyzed by p53 IHC and fluorescence in situ hybridization. Nuclear p53 accumulation was found in 10.1% of patients including 1.4% with high‐level and 8.7% with low‐level immunostaining. TP53 sequencing revealed that 17 of 22 (77%) cases with high‐level p53 immunostaining, but only 3% (1 of 31) low‐level p53 cases carried putative dominant‐negative mutations. TP53 deletions occurred in 14.8% of cancers. Both deletions and protein accumulation were linked to unfavorable tumor phenotype and prostate specific antigen (PSA) recurrence (p < 0.0001 each). The combination of both methods revealed subgroups with remarkable differences in their clinical course. Tumors with either TP53 deletion (14%) or low‐level p53 positivity (8.7%) had identical risks of PSA recurrence, which were markedly higher than in cancers without p53 alterations (p < 0.0001). Tumors with both p53 deletion and low‐level p53 positivity (1.5%) had a worse prognosis than patients with only one of these alterations (p < 0.0001). Tumors with strong p53 immunostaining or homozygous inactivation through deletion of one allele and disrupting translocation involving the second allele had the worst outcome, independent from clinical and pathological parameters. These data demonstrate a differential clinical impact of various TP53 alterations in prostate cancer. Strong p53 immunostaining—most likely accompanying dominant negative or oncogenic p53 mutation—has independent prognostic relevance and may thus represent a clinical useful molecular feature of prostate cancer.
The mediating role of disgust sensitivity and thought‐action fusion between religiosity and obsessive compulsive symptoms
Authors: Inozu Mujgan , Ulukut Fulya Ozcanli , Ergun Gokce , Alcolado Gillian M.
Published: February 2014

Psychological theories of obsessions and compulsions have long recognised that strict religious codes and moral standards might promote thought‐action fusion (TAF) appraisals. These appraisals have been implicated in the transformation of normally occurring intrusions into clinically distressing obsessions. Furthermore, increased disgust sensitivity has also been reported to be associated with obsessive compulsive (OC) symptoms. No research, however, has investigated the mediating roles of TAF and disgust sensitivity between religiosity and OC symptoms. This study was composed of 244 undergraduate students who completed measures of OC symptoms, TAF, disgust sensitivity, religiosity and negative effect. Analyses revealed that the relationship between religiosity and OC symptoms was mediated by TAF and disgust sensitivity. More importantly, the mediating role of TAF was not different across OC symptom subtypes, whereas the mediating role of disgust sensitivity showed different patterns across OC symptom subtypes. These findings indicate that the tendency for highly religious Muslims to experience greater OC symptoms is related to their heightened beliefs about disgust sensitivity and the importance of thoughts.
Bone segmentation and 3D visualization of CT images for traumatic pelvic injuries
Authors: Wu Jie , Belle Ashwin , Hargraves Rosalyn H , Cockrell Charles , Tang Yang , Najarian Kayvan
Published: February 2014

Pelvic bone segmentation is a vital step in analyzing pelvic CT images, which assists physicians with diagnostic decision making in cases of traumatic pelvic injuries. Due to the limited resolution of the original CT images and the complexity of pelvic structures and their possible fractures, automatic pelvic bone segmentation in multiple CT slices is very difficult. In this study, an automatic pelvic bone segmentation approach is proposed using the combination of anatomical knowledge and computational techniques. It is developed for solving the problem of accurate and efficient bone segmentation using multiple consecutive pelvic CT slices obtained from each patient. Our proposed segmentation method is able to handle variation of bone shapes between slices there by making it less susceptible to inter‐personal variability between different patients' data. Moreover, the designed training models are validated using a cross‐validation process to demonstrate the effectiveness. The algorithm's capability is tested on a set of 20 CT data sets. Successful segmentation results and quantitative evaluations are present to demonstrate the effectiveness and robustness of proposed algorithm, well suited for pelvic bone segmentation purposes.
Automated texture‐based characterization of fibrosis and carcinoma using low‐dose lung CT images
Authors: Devan Lakshmi , Santosham Roy , Hariharan Ranganathan
Published: February 2014

Lung cancer is the most common cause of cancer deaths worldwide and account for 1.38 million deaths per year. Patients with lung cancer are often misdiagnosed as pulmonary tuberculosis (TB) leading to delay in the correct diagnosis as well as exposure to inappropriate medication. The diagnosis of TB and lung cancer can be difficult as symptoms of both diseases are similar in computed tomography (CT) images. However, treating TB leads to inflammatory fibrosis in some of the patients. There comes the need of an efficient computer aided diagnosis (CAD) of the fibrosis and carcinoma diseases. To design a fully automated CAD for characterizing fibrous and carcinoma tissues without human intervention using lung CT images. The 18 subjects in this study include seven healthy, two fibrosis and eight carcinoma, and one necrosis cases. The dataset is built by CT cuts representing healthy is 113, fibrosis is 103, necrosis is 39, and carcinoma is 185 totalling 440 images. The gray‐level spatial dependence matrix and gray level run length matrix approach are used for extracting texture‐based features. These features are given to neural network classifier and statistical classifier. These classifier performances are evaluated using receiver‐operating characteristics (ROC). The proposed method characterizes these tissues without human intervention. Sensitivity, specificity, precision, and accuracy followed by ROC curves were obtained and also studied. Thus, the proposed automated image‐based classifier could act as a precursor to histopathological analysis, thereby creating a way to class specific treatment procedures.
GRP78 Mediates Cell Growth and Invasiveness in Endometrial Cancer
Authors: Calì Gaetano , Insabato Luigi , Conza Domenico , Bifulco Giuseppe , Parrillo Luca , Mirra Paola , Fiory Francesca , Miele Claudia , Raciti Gregory Alexander , Di Jeso Bruno , Terrazzano Giuseppe , Beguinot Francesco , Ulianich Luca
Published: February 2014

Recent studies have indicated that endoplasmic reticulum stress, the unfolded protein response activation and altered GRP78 expression can play an important role in a variety of tumors development and progression. Very recently we reported for the first time that GRP78 is increased in endometrial tumors. However, whether GRP78 could play a role in the growth and/or invasiveness of endometrial cancer cells is still unknown. Here we report that the silencing of GRP78 expression affects both cell growth and invasiveness of Ishikawa and AN3CA cells, analyzed by the (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide) and transwell migration assay, respectively. At variance with Ishikawa cells, AN3CA cells showed, besides an endoplasmic reticulum, also a plasma membrane GRP78 localization, evidenced by both immunofluorescence and cell membrane biotinylation experiments. Intriguingly, flow cytometry experiments showed that the treatment with a specific antibody targeting GRP78 C‐terminal domain caused apoptosis in AN3CA but not in Ishikawa cells. Induction of apoptosis in AN3CA cells was not mediated by the p53 pathway activation but was rather associated to reduced AKT phosphorylation. Interestingly, immunofluorescence analysis evidenced that endometrioid adenocarcinoma tissues displayed, similarly to AN3CA cells, also a GRP78 plasma membrane localization. These data suggest that GRP78 and its plasma membrane localization, might play a role in endometrial cancer development and progression and might constitute a novel target for the treatment of endometrial cancer. J. Cell. Physiol. 229: 1417–1426, 2014. © 2014 Wiley Periodicals, Inc.
Dynamics and constraints of enzyme evolution
Authors: Kaltenbach Miriam , Tokuriki Nobuhiko
Published: February 2014

The wealth of distinct enzymatic functions found in nature is impressive and the on‐going evolutionary divergence of enzymatic functions continues to generate new and efficient catalysts, which can be seen through the recent emergence of enzymes able to degrade xenobiotics. However, recreating such processes in the laboratory has been met with only moderate success. What are the factors that lead to suboptimal research outputs? In this review, we discuss constraints on enzyme evolution, which can restrict evolutionary trajectories and lead to evolutionary dead‐ends. We highlight recent studies that have used experimental evolution to mimic different aspects of enzymatic adaptation under simple, controlled settings to shed light on evolutionary dynamics and constraints. A better understanding of these constraints will lead to the development of more efficient strategies for directed evolution and enzyme engineering. J. Exp. Zool. (Mol. Dev. Evol.) 322B: 468–487, 2014. © 2014 Wiley Periodicals, Inc.
Hepatitis C virus serine protease: synthesis of radioactive and stable isotope‐labeled potent inhibitors
Authors: Latli Bachir , Hrapchak Matt , Gorys Vida , Llinàs‐Brunet Montse , Campbell Scot S. , Song Jinhua , Senanayake Chris H.
Published: February 2014

Drug candidates labeled with radioactive and stable isotopes are required for absorption, distribution, metabolism, and excretion (ADME) studies, pharmacokinetics, autoradiography, bioanalytical, and other research activities. The findings from these studies are crucial in the development of a drug candidate and its approval for human use. Herein, we report the synthesis of potent and selective hepatitis C virus serine protease inhibitors related to BILN 2061 and BI 201335 labeled with radioactive and stable isotopes. Synthetic efforts were focused on the common substituted thiazole moiety, which is easily accessible via a Hantzsch's reaction of α‐bromoketones and mono‐substituted thioureas. In the radioactive synthesis, commercially available carbon‐14 thiourea was utilized to prepare mono‐substituted thioureas, which upon condensation with α‐bromoketones in isopropanol followed by ester hydrolysis gave the desired carbon‐14‐labeled protease inhibitors. The same strategy was used to prepare these inhibitors labeled with stable isotopes. Mono‐substituted thioureas were obtained from commercially available deuterium‐labeled intermediates and then condensed with α‐bromoketones followed by ester hydrolysis to give the deuterium‐labeled inhibitors.
Clinical characteristics and genetic diversity of noroviruses in adults with acute gastroenteritis in Beijing, China in 2008–2009
Authors: Tian Geng , Jin Miao , Li Huiying , Li Quanrui , Wang Jing , Duan Zhao‐jun
Published: February 2014

Norovirus (NoV) infections that cause acute gastroenteritis are commonly observed during colder months. This study was conducted to investigate the clinical features and molecular epidemiology of NoVs in adult outpatients with acute gastroenteritis in Beijing, China from August 2008 to July 2009. Five hundred nineteen patients were enrolled, their stool specimens were collected, and 136 (26.2%) were positive for NoV. The elderly were found to be more susceptible to NoVs than other age groups. The greatest number of gastroenteritis cases associated with occurred in October. Six GI and eleven GII NoV genotypes were isolated; among these, the GII.4 genotype was most prevalent (70/140 and 50% were the 2006b variant). The elderly were more susceptible to the GII.4 genotype than to other genotypes. Greater numbers of neutrophils in the peripheral blood were observed in the NoV infected group than in uninfected control group. However, the levels of neutrophils and leukocytes in the non‐GII.4 patients infected with NoV were higher than those of the GII.4‐infected patients. The data highlight the role of NoV as a primary agent responsible for gastroenteritis in adults in Beijing, China. J. Med. Virol. 86:1235–1242, 2014. © 2014 Wiley Periodicals, Inc.
Prevalence, genetic drift of haemagglutinin, and antiviral resistance of influenza A/H3N2 viruses circulating in Shanghai in children during 2009–2012
Authors: Cai Jiehao , Wang Xiangshi , Zhao Baihui , Yao Weilei , Wang Xiaohong , Zhu Qirong , Zeng Mei
Published: February 2014

Influenza A/H3N2 viruses are associated with severe epidemics. Antiviral resistance and continued antigenic drift are the major concerns regarding prophylaxis and treatment of influenza. The objectives of this study were to investigate the prevalence and frequency of antiviral drug resistance in influenza A/H3N2 viruses circulating among Shanghainese children from June 2009 to May 2012 and to understand the genetic evolution of the hemagglutinin (HA) epitopes. Nasopharyngeal/throat swabs were collected from outpatients with influenza‐like illness. Of the 3,475 children tested, 344 (9.9%) were positive for influenza A/H3N2 viruses. Epidemics of influenza A/H3N2 occurred in July–September 2009, August 2010–January 2011, and November 2011–May 2012. The 71 A/H3N2‐positive specimens were sequenced to characterize the genotypic antiviral resistance and genetic drift in the HA epitopes. All of the 71 A/H3N2 viruses sequenced were genotypically resistant to adamantine but sensitive to oseltamivir. The HA1 sequence analysis revealed that the A/H3N2 viruses underwent constant mutations in the HA antigenic sites over the three seasons compared with the corresponding vaccine strains, and amino acid changes in at least three epitopes were observed each season. Phylogenic analyses indicated that the A/H3N2 strains circulating in Shanghai fell into clades different from those of the corresponding seasonal vaccine strains and were grouped into the A/Perth/16/2009 genetic clade and the A/Victoria/208/2009 genetic clades 3B, 3C, and 5. The continuous monitoring of genetic drift and antiviral resistance of influenza viruses is important for the management of influenza and for updating the vaccine composition. J. Med. Virol. 86:1026–1033, 2014. © 2014 Wiley Periodicals, Inc.
Externalizing and Internalizing Subtypes of Posttraumatic Psychopathology and Anger Expression
Authors: Castillo Diane T. , Joseph Jeremy S. , Tharp Andra T. , C'de Baca Janet , Torres‐Sena Lorraine M. , Qualls Clifford , Miller Mark W.
Published: February 2014

Subtypes of posttraumatic psychopathology were replicated and extended in 254 female veterans with posttraumatic stress disorder (PTSD). Cluster analyses on Minnesota Multiphasic Personality Inventory‐2 and Personality Psychopathology Five scales (Harkness, McNulty, & Ben‐Porath, ) yielded internalizing and externalizing psychopathology dimensions, with a third low psychopathology group (simple PTSD). Externalizers were higher than the internalizers and the simple PTSD groups on the antisocial, substance, and aggression scales; internalizers were higher on depression and anxiety scales. Further validation included an independent measure of psychopathology to examine anger (Buss‐Durkee Hostility Inventory, [BDHI]; Buss & Durkee, ). Externalizers were higher on extreme behavioral anger scales (assault and verbal hostility); and externalizers and internalizers were higher than the simple PTSD subjects on other anger scales. Positive correlations between the BDHI scales and the PTSD symptom of “irritability and anger outbursts” were found across scales in the total sample (range: r = .19–.36), on the assault scale in externalizers (r = .59), and the verbal hostility scale in both internalizers (r = .30) and simple PTSD (r = .37) groups, suggesting the broad utility of the symptom in the diagnosis. The results demonstrate the generalizability of the internalizing/externalizing typology to the female veteran population and highlight clinically relevant distinctions in anger expression within PTSD.
Synthesis and On‐Demand Gelation of Multifunctional Poly(ethylene glycol)‐Based Polymers
Authors: Sokolovskaya Ekaterina , Barner Leonie , Bräse Stefan , Lahann Jörg
Published: February 2014

The synthesis of a novel photoreactive poly(ethylene glycol) (PEG)‐based polymer with caged carbonyl groups is reported. We further demonstrate its use for the on‐demand fabrication of hydrogels. For rapid gelation, a hydrazide‐functionalized PEG is used as the second component for the hydrogel preparation. The photoreactive PEG‐based polymer is designed for controlled cleavage of the protecting groups upon exposure to UV light releases free aldehyde moieties, which readily react with hydrazide groups in situ. This hydrogel system may find applications in controlled release drug delivery applications, when combined with in situ gelation. Furthermore, the possibility of forming gels specifically upon UV irradiation gives an opportunity for 3D fabrication of degradable scaffolds.

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A novel synthetic oleanane triterpenoid suppresses adhesion, migration, and invasion of highly metastatic melanoma cells by modulating gelatinase signaling axis
Authors: Sinha Dona , Dutta Kaustav , Ganguly Kirat K. , Biswas Jaydip , Bishayee Anupam
Published: February 2014

A methyl derivative natural triterpenoid amooranin (methyl‐25‐hydroxy‐3‐oxoolean‐12‐en‐28‐oate, AMR‐Me) has been found to possess antiproliferative, proapoptotic, and antiinflammatory effects against established tumor cells. Large‐scale synthesis of pure AMR‐Me has eliminated the need of the natural phytochemical for further development of AMR‐Me as an anticancer drug. Metastatic melanoma is a fatal form of cutaneous malignancy with poor prognosis and limited therapeutic options. It was hypothesized that antitumor pharmacological effect of AMR‐Me could be linked to AMR‐Me‐mediated suppression of the metastatic potential of B16F10 murine melanoma. AMR‐Me was assessed for its antimetastatic efficacy by cell adhesion, migration, and invasion assays in B16F10 cells. The signaling crosstalk was explored by gelatin zymography, Western blot, ELISA, and immunocytochemistry. The results elicited that AMR‐Me was successful in restricting the adhesion, migration, and invasion of highly metastatic cells. The antimetastatic potential of this compound may be attributed to the reduced expression of membrane type 1 metalloproteinase (MT1‐MMP) and matrix metalloproteinases (MMP‐2 and MMP‐9). AMR‐Me was found to downregulate vascular endothelial growth factor (VEGF)/phosphorylated forms of focal adhesion kinase (pFAK397)/Jun N‐terminus kinase (pJNK)/extracellular signal‐regulated kinase (pERK). This, in turn, inhibited transcription factor nuclear factor‐κB (NF‐κB) and transactivation of MMPs. Moreover, the activation of tissue inhibitors of metalloproteinases (TIMP‐1 and TIMP‐2) might have influenced the downmodulation of MT1‐MMP, MMP‐2, and MMP‐9. AMR‐Me suppresses the activity of MT1‐MMP, MMP‐2, and MMP‐9 by downregulation of VEGF/pFAK397/pJNK/pERK/NF‐κB and activation of TIMP‐1 and TIMP‐2 in metastatic melanoma cell line, B16F10. AMR‐Me has the potential as an effective anticancer drug for metastatic melanoma which is a dismal disease. © 2014 Wiley Periodicals, Inc.
Qualitative analysis for a competition model with B‐D functional response and numerical simulation
Authors: Jiang Hongling , Wu Jianhua , Wang Lijuan , Li Jian , Guo Gaihui
Published: February 2014

In this article, a competition model with Beddington–DeAngelis functional response is discussed. By the fixed point index theory, some sufficient conditions for the existence of positive solutions are obtained. Moreover, by the regularity theory and perturbation technique, the existence, uniqueness, and stability of positive solutions are established. Our studies show that the competition can be controlled by the intrinsic growth rates and competition coefficients of two species. Especially, one sufficient condition that the system has a unique globally asymptotically stable positive solution is gained. Finally, some numerical simulations are given to support and supplement our theoretical results.Copyright © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 30: 1575–1594, 2014
Superconvergence and gradient recovery for a finite volume element method for solving convection‐diffusion equations
Authors: Zhang Tie , Sheng Ying
Published: February 2014

We study the superconvergence of the finite volume element (FVE) method for solving convection‐diffusion equations using bilinear trial functions. We first establish a superclose weak estimate for the bilinear form of FVE method. Based on this estimate, we obtain the H1‐superconvergence result: . Then, we present a gradient recovery formula and prove that the recovery gradient possesses the ‐order superconvergence. Moreover, an asymptotically exact a posteriori error estimate is also given for the gradient error of FVE solution.Copyright © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 30: 1152–1168, 2014
Self‐Compassion and Risk Behavior Among People Living With HIV/AIDS
Authors: Dawson Rose Carol , Webel Allison , Sullivan Kathleen M. , Cuca Yvette P. , Wantland Dean , Johnson Mallory O. , Brion John , Portillo Carmen J. , Corless Inge B. , Voss Joachim , Chen Wei‐Ti , Phillips J. Craig , Tyer‐Viola Lynda , Rivero‐Méndez Marta , Nicholas Patrice K. , Nokes Kathleen , Kemppainen Jeanne , Sefcik Elizabeth , Eller Lucille Sanzero , Iipinge Scholastika , Kirksey Kenn , Chaiphibalsarisdi Puangtip , Davila Nancy , Hamilton Mary Jane , Hickey Dorothy , Maryland Mary , Reid Paula , Holzemer William L.
Published: February 2014

Sexual risk behavior and illicit drug use among people living with HIV/AIDS (PLWHA) contribute to poor health and onward transmission of HIV. The aim of this collaborative multi‐site nursing research study was to explore the association between self‐compassion and risk behaviors in PLWHA. As part of a larger project, nurse researchers in Canada, China, Namibia, Puerto Rico, Thailand and the US enrolled 1211 sexually active PLWHA using convenience sampling. The majority of the sample was male, middle‐aged, and from the US. Illicit drug use was strongly associated with sexual risk behavior, but participants with higher self‐compassion were less likely to report sexual risk behavior, even in the presence of illicit drug use. Self‐compassion may be a novel area for behavioral intervention development for PLWHA. © 2014 Wiley Periodicals, Inc.
Mechanical properties and morphology of intumescent flame retardant filled polypropylene composites
Authors: Liang Ji‐Zhao , Li Feng‐Jiao , Feng Jin‐Qing
Published: February 2014

The intumescent flame retardant (IFR) filled polypropylene (PP) composites were prepared using a twin‐screw extruder. The tensile and impact fracture behavior of the composites were measured at room temperature. It was found that the Young's modulus increased roughly, while the tensile strength decreased slightly with increasing the IFR weight fraction; the toughening effect of the filler on the PP resin was significant. Both the V‐notched Izod impact strength and the V‐notched Charpy impact strength of the PP/IFR composites showed a nonlinear increase with increasing the filler weight fraction (φf) as φf was less than 20%, then it decreased. The limited oxygen index of the composites increases nonlinearly with increasing φf. The relationship between them obeyed a quadratic equation. The impact fracture surface was observed by means of a scanning electronic microscope to understand the toughening mechanisms for the composite systems. Copyright © 2014 John Wiley & Sons, Ltd.
The production of carbon nanotube reinforced poly(vinyl) butyral nanofibers by the Forcespinning® method
Authors: Weng Baicheng , Xu Fenghua , Garza George , Alcoutlabi Mataz , Salinas Alfonso , Lozano Karen
Published: February 2014

Poly(vinyl) butyral (PVB) nanofibers (NFs) and carbon nanotube (CNT) reinforced PVB NF composites were developed by using the Forcespinning® technology. PVB was dissolved in a mixture of ethanol and methanol (7:3 wt/wt) at various concentrations, and the solutions were spun at rotational speeds varying between 3,000 and 9,000 rpm. The CNT/PVB solutions were prepared using the same solvent ratio with varying the concentration of CNTs. The results show that the diameter of the PVB fibers increased with increasing rotational speed; however the standard deviation of the fiber diameter distribution decreased. The morphology and thermal properties of the developed fiber systems were studied by DSC, TGA, Raman, and FTIR. The effect of CNT on the mechanical properties of the developed fibers was investigated by carrying out tensile tests at different strain rates. Raman and FTIR analyses indicate a noncovalent π–π stacking interactions and hydrogen bonding between CNT and the PVB NFs. Adding CNT to the PVB NF matrix resulted in improved tensile strength by 150%. POLYM. ENG. SCI., 55:81–87, 2015. © 2014 Society of Plastics Engineers
Thermoelectric properties of Cu2Ga4Te7 based compounds with Zn substitution for Cu and Ga
Authors: Chen Shaoping , Ren Wei , Meng Qingsen , Liu Xianglian , Yang Jiangfeng , Cui Jiaolin
Published: February 2014

We present two series of Cu2Ga4Te7‐based compounds with Zn substituting for Cu (Cu‐poor) and Ga (Ga‐poor), and have observed enhanced thermoelectric performance. Generally, the Seebeck coefficient (α) and lattice thermal conductivity (κL) increase and electrical conductivity (σ) decreases with the Zn content increasing. The variation in electrical properties might be mainly due to the formation of antisite defects ( and ), the acceptors. The defects increase the local density of states (DOS) near the Fermi level and effective mass, leading to the increase in α, while on the other hand, they widen the bandgap (Eg) leading to the degradation of the electrical conductivity. The gradual enhancement in κL is attributed to the reduced phonon scattering resulting from the decrease in vacancy concentration. As a result, we attained the maximum ZT value of 0.46 for Cu‐CGT and 0.47 for Ga‐CGT at ∼770 K with a proper Zn content, which is about 20–22% higher than that of intrinsic Cu2Ga4Te7.
Adjusting for centre heterogeneity in multicentre clinical trials with a time‒to‒event outcome
Authors: Munda Marco , Legrand Catherine
Published: February 2014

Conducting a clinical trial at multiple study centres raises the issue of whether and how to adjust for centre heterogeneity in the statistical analysis. In this paper, we address this issue for multicentre clinical trials with a time‒to‒event outcome. Based on simulations, we show that the current practice of ignoring centre heterogeneity can be seriously misleading, and we illustrate the performances of the frailty modelling approach over competing methods. A special attention is paid to the problem of misspecification of the frailty distribution. The appendix provides sample codes in R and in SAS to perform the analyses in this paper. Copyright © 2014 John Wiley & Sons, Ltd.
Optimization of individualized dynamic treatment regimes for recurrent diseases
Authors: Huang Xuelin , Ning Jing , Wahed Abdus S.
Published: February 2014

Patients with cancer or other recurrent diseases may undergo a long process of initial treatment, disease recurrences, and salvage treatments. It is important to optimize the multi‐stage treatment sequence in this process to maximally prolong patients' survival. Comparing disease‐free survival for each treatment stage over penalizes disease recurrences but under penalizes treatment‐related mortalities. Moreover, treatment regimes used in practice are dynamic; that is, the choice of next treatment depends on a patient's responses to previous therapies. In this article, using accelerated failure time models, we develop a method to optimize such dynamic treatment regimes. This method utilizes all the longitudinal data collected during the multi‐stage process of disease recurrences and treatments, and identifies the optimal dynamic treatment regime for each individual patient by maximizing his or her expected overall survival. We illustrate the application of this method using data from a study of acute myeloid leukemia, for which the optimal treatment strategies for different patient subgroups are identified. Copyright © 2014 John Wiley & Sons, Ltd.
The influence of etofenprox on narrow clawed crayfish (Astacus leptodactylus Eschscholtz, 1823): Acute toxicity and sublethal effects on histology, hemolymph parameters, and total hemocyte counts
Authors: Benli Aysel Caglan Karasu
Published: February 2014

The acute and sublethal effects of etofenprox, a nonester pyrethroid, was determined in narrow‐clawed crayfish (Astacus leptodactylus Eschscholtz, 1823). Semistatic bioassay procedures were followed in both experiments, and the 24, 48, 72, and 96 h LC50 values (with 95% confidence limits) of technical etofenprox for crayfish were calculated as 0.68, 0.61, 0.45, and 0.41 µg/L, respectively based on Finney's probit analysis. Two concentrations of etofenprox (0.04 and 0.1 µg/L) were tested to determine sublethal effects due to 96 hours exposure. After exposure to sublethal etofenprox, hemolymph glucose, and lactate levels increased while total hemocyte counts and sodium levels decreased (p < 0.05). Hemolymph calcium, potassium, magnesium, and chloride concentrations did not change significantly. Histological alterations were evident in the gills and hepatopancreas after exposure to sublethal etofenprox concentrations. Lamellar hyperplasia and lining in the afferent and efferent branchial vessels were recorded in gills; whilst tubule necrosis was obvious in hepatopancreas. Etofenprox was found to be very highly toxic to crayfish, a nontarget organism. Exposure to sublethal concentrations for 96 h affected circulating hemocytes and hemolymph stress parameters via histological response, to compansate for the adverse effects of etofenprox. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 887–894, 2015.
Opportunistic interference management: a new approach for multiantenna downlink cellular networks
Authors: Kiskani Mohsen Karimzadeh , Wang Zheng , Sadjadpour Hamid R. , Oviedo Jose A. , Garcia‐Luna‐Aceves Jose Joaquin
Published: February 2014

A new approach for multiantenna broadcast channels in cellular networks based on multiuser diversity concept is introduced. The technique called opportunistic interference management achieves dirty paper coding capacity asymptotically with minimum feedback required. When there are K antennas at the base station with M mobile users in the cell, the proposed technique only requires K integer numbers related to channel state information between mobile users and base station. The encoding and decoding complexity of this scheme is the same as that of point‐to‐point communications, which makes the implementation of this technique easy. An antenna selection scheme is proposed at the base station to reduce the minimum required mobile users significantly at the expense of reasonable increase in feedback. In order to guarantee fairness, a new algorithm is presented that incorporates opportunistic interference management into existing Global System for Mobile communications (GSM) standard. Copyright © 2014 John Wiley & Sons, Ltd.
Fluoroferrates with (dabcoH2)2+ or (dabcoH)+ Cations
Authors: Darmograi Ganna , Jouffret Laurent , Hémon‐Ribaud Annie , Leblanc Marc , Dujardin Gilles , Maisonneuve Vincent , Lhoste Jerome
Published: February 2014

Four new hybrid fluoroferrates synthesized with 1,4‐diazabicyclooctane (dabco) are discussed. They were obtained through the use of conventional solvothermal synthesis in Teflon vessels to explore the composition space diagram of the (Fe2+,Fe3+)‐dabco‐HFaq. chemical system with ethanol or dimethylformamide as solvent. These Class I hybrid fluorides exhibit isolated hydrated and/or fluorinated iron entities associated to mono or diprotonated amines according to the synthesis conditions. Their structures were determined from single crystal diffraction: (dabcoH2)[FeIII2F8(H2O)2] (I), triclinic, space group P$\bar{1}$, Z = 2, a = 7.1657(2) Å, b = 7.6031(2) Å, c = 13.1497(3) Å, α = 73.631(1)°, β = 76.210(1)°, γ = 84.286(1)°, V = 667.1(1) Å3, R = 0.0299; (dabcoH2)2[FeIII2F10]·2H2O (II), orthorhombic, space group Pbca, Z = 4, a = 12.9801(7) Å, b = 11.4624(6) Å, c = 13.8641(7) Å, V = 2062.7(2) Å3, R = 0.0425; (dabcoH)4[FeIII2F10]·10H2O (III), triclinic, space group P$\bar{1}$, Z = 1, a = 8.921(3) Å, b = 9.468(4) Å, c = 13.452(4) Å, α = 76.87(2)°, β = 74.62(2)°, γ = 74.86(2)°, V = 1042.2(6) Å3, R = 0.0549; (dabcoH)[(FeII(H2O)6)(FeIIIF6)] (IV), trigonal, space group P31c, Z = 2, a = 9.2866(2) Å, c = 10.2401(2) Å, V = 764.8(3) Å3, R = 0.0252. The paper focuses on structural descriptions, environment of dabco cations or iron species, and hydrogen bonding modes in the light of literature examples.
Clinical, biochemical and molecular analysis of 13 Japanese patients with β‐ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation
Authors: Nakajima Yoko , Meijer Judith , Dobritzsch Doreen , Ito Tetsuya , Meinsma Rutger , Abeling Nico G. G. M. , Roelofsen Jeroen , Zoetekouw Lida , Watanabe Yoriko , Tashiro Kyoko , Lee Tomoko , Takeshima Yasuhiro , Mitsubuchi Hiroshi , Yoneyama Akira , Ohta Kazuhide , Eto Kaoru , Saito Kayoko , Kuhara Tomiko , van Kuilenburg André B. P.
Published: February 2014

β‐ureidopropionase (βUP) deficiency is an autosomal recessive disease characterized by N‐carbamyl‐β‐amino aciduria. To date, only 16 genetically confirmed patients with βUP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese βUP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant βUP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (≤ 1.3 %). Conversely, βUP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non‐coding region of the UPB1 gene. Analysis of a human βUP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that βUP deficiency is not as rare as generally considered and screening for βUP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.
Effects of belowground vertical distribution of a herbivore on plant biomass and survival in Lolium perenne
Authors: Tsunoda Tomonori , Kachi Naoki , Suzuki Jun‐Ichirou
Published: February 2014

Root herbivory affects plant performance, but the effects are not well understood. We tested the effects of the vertical distribution of a root‐feeding beetle larva (Anomala cuprea) by restricting its access to the top, middle, or bottom zone in pots of perennial ryegrass (Lolium perenne) or by allowing unrestricted access. We predicted that plant mortality, biomass, and biomass allocation should change with the zone of root herbivory, because both the magnitude of root loss and the consequences of such loss are specific to the point of damage. Seven of nine plants died in each treatment in which the larvae had access to the top zone. In contrast, no plants died when larvae occupied the middle or bottom zones. Plants were killed when the larvae grazed the root base and severed the shoots from the roots. Moreover, total plant biomass and biomass allocation to roots were significantly lower when the larvae were confined to the top and middle feeding zones. The greatest number of roots were removed when the larvae occupied the top feeding zone. Thus, the vertical distribution of a belowground herbivore is crucially important to plant fate. In nature, most belowground herbivores are concentrated near the soil surface, and thus the effects of belowground herbivory are often more severe than the effects of aboveground herbivory.
Application of EPR Spectroscopy and DSC for Oxidative Stability Studies of Nigella sativa and Lepidium sativum Seed Oil
Authors: Naik Azza , Meda V. , Lele S. S.
Published: February 2014

Food products incorporating oil rich in polyunsaturated fatty acids are known to become easily rancid. In order to delay the process of oxidation there is a need to develop analytical methods that accurately estimate the antioxidant potential of the oil and predict its oxidative stability. Thus, the present work investigated Lepidium sativum and Nigella sativa seed oil as a source of natural antioxidants. Further, the effect of blending the two oils on the oxidative stability of the unsaturated L. sativum oil was also studied. Electro‐paramagnetic resonance (EPR) spectroscopy showed 100 % 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical quenching by both the oils at a concentration of 5 % w/v oil in benzene thereby establishing the anti‐oxidant potential of both the oils. Differential scanning calorimetry (DSC) studies showed addition of N. sativa oil to L. sativum oil enhanced its oxidation onset temperature, a relevant indicator of oil stability, thereby making N. sativa a source of natural antioxidants. Consequently, the DSC and EPR spectroscopy techniques so developed can find application in shelf life studies of oil.
Speleothem evidence for late Holocene climate variability and floods in Southern Greece
Authors: Finné Martin , Bar-Matthews Miryam , Holmgren Karin , Sundqvist Hanna S. , Liakopoulos Ilias , Zhang Qiong
Published: February 2014

We present stable isotope data (δ18O, δ13C) from a detrital rich stalagmite from Kapsia Cave, the Peloponnese, Greece. The cave is rich in archeological remains and there are reasons to believe that flooding of the cave has directly affected humans using the cave. Using a combination of U–Th and 14C dating to constrain a site-specific correction factor for (232Th/238U) detrital molar ratio, a linear age model was constructed. The age model shows that the stalagmite grew during the period from ca. 950 BC to ca. AD 830. The stable oxygen record from Kapsia indicates cyclical changes of close to 500 yr in precipitation amount, with rapid shifts towards wetter conditions followed by slowly developing aridity. Superimposed on this signal, wetter conditions are inferred around 850, 700, 500 and 400–100 BC, and around AD 160–300 and AD 770; and driest conditions are inferred to have occurred around 450 BC, AD 100–150 and AD 650. Detrital horizons in the stalagmite indicate that three major floods took place in the cave at 500 BC, 70 BC and AD 450. The stable carbon isotope record reflects changes in biological activity being a result of both climate and human activities.
AN ACTUARIAL BALANCE SHEET MODEL FOR DEFINED BENEFIT PAY-AS-YOU-GO PENSION SYSTEMS WITH DISABILITY AND RETIREMENT CONTINGENCIES
Authors: Ventura-Marco Manuel , Vidal-Meliá Carlos
Published: February 2014

In this paper, we develop a theoretical basis for drawing up a “Swedish” type actuarial balance sheet for a defined benefit pay-as-you-go (DB PAYG) scheme with retirement and disability benefits. Our model enables us to obtain the system's expected average turnover duration, measure the scheme's solvency and explore the phenomenon identified as “pension reclassification”, a widespread practice that masks the system's real status unless further pension information becomes available. The model is clearly linked to actuarial practice in social security and gives partial support to the practical adaptation of Swedish methodology carried out by OSFI (2012) in applying the concept of the contribution asset to the Canadian Pension Plan (CPP) balance sheet, which includes disability and survivor benefits.
Stability analysis for the onset of thermoacoustic oscillations in a gas-filled looped tube
Authors: Hyodo H. , Sugimoto N.
Published: February 2014

This paper develops a stability analysis for the onset of thermoacoustic oscillations in a gas-filled looped tube with a stack inserted, subject to a temperature gradient. Analysis is carried out based on approximate theories for a thermoviscous diffusion layer derived from the thermoacoustic-wave equation taking account of the temperature dependence of the viscosity and the heat conductivity. Assuming that the stack consists of many pores axially and that the thickness of the diffusion layer is much thicker than the pore radius, the diffusion wave equation with higher-order terms included is applied for the gas in the pores of the stack. For the gas outside of the pores, the theory of a thin diffusion layer is applied. In a section called the buffer tube over which the temperature relaxes from that at the hot end of the stack to room temperature, the effects of the temperature gradient are taken into account. With plausible temperature distributions specified on the walls of the stack and the buffer tube, the solutions to the equations in both theories are obtained and a frequency equation is finally derived analytically by matching the conditions at the junctions between the various sections. Seeking a real solution to the frequency equation, marginal conditions of instability are obtained numerically not only for the one-wave mode but also for the two-wave mode, where the tube length corresponds to one wavelength and two wavelengths, respectively. It is revealed that the marginal conditions depend not only on the thickness of the diffusion layer but also on the porosity of the stack. Although the toroidal geometry allows waves to be propagated in both senses along the tube, it is found that the wave propagating in the sense from the cold to the hot end through the stack is always greater, so that a travelling wave in this sense emerges as a whole. The spatial and temporal variations of excess pressure and mean axial velocity averaged over the cross-section of a flow passage are displayed for the two modes of oscillations at the marginal state. The spatial distribution of mean acoustic energy flux (acoustic intensity) over one period is also shown. It is unveiled that the energy flux is generated only in the stack, and it decays slowly in the other sections by lossy effects due to a boundary layer. Mechanisms for the generation of the acoustic energy flux are also discussed.
Discourse Grammar, the dual process model, and brain lateralization: some correlations
Authors: HEINE BERND , KUTEVA TANIA , KALTENBÖCK GUNTHER
Published: February 2014

abstract

Some more recent lines of research converge on claiming that human cognitive behavior in general and linguistic discourse in particular cannot reasonably be reduced to one monolithic system of cognitive activity. What this research suggests, rather, is that this behavior exhibits a dualistic organization. In the present paper, two frameworks representing this tradition are contrasted, namely Discourse Grammar and the dual process model. The former rests on observations on language structure and language use, while the latter was developed on the basis of neurolinguistic observations. The two frameworks converge on claiming that there is a significant correlation between linguistic categorization and hemisphere-based brain activity. The present paper argues that this correlation can be related to contrasting linguistic functions associated with each of the two hemispheres.
Micro-architectural changes in cancellous bone differ in female and male C57BL/6 mice with high-fat diet-induced low bone mineral density
Authors: Gautam Jyoti , Choudhary Dharmendra , Khedgikar Vikram , Kushwaha Priyanka , Singh Ravi Shankar , Singh Divya , Tiwari Swasti , Trivedi Ritu
Published: February 2014

The relationship between fat and bone mass at distinct trabecular and cortical skeletal compartments in a high-fat diet (HFD) model was studied. For this, C57BL/6 mice were assigned to four groups of eight animals each. Two groups, each of males and females, received a standard chow diet while the remaining other two groups received the HFD for a period of 10 weeks. Male mice on the HFD were heavier and gained more weight (15·8 %;P<  0·05)v.those on the control diet or when compared with the female rats fed the HFD. We observed an increased lipid profile in both males and females, with significantly higher lipid levels (about 20–25 %;P< 0·01) in males. However, glucose intolerance was more pronounced in females than males on the HFD (about 30 %;P< 0·05). The micro-architectural assessment of bones showed that compared with female mice on the HFD, male mice on the HFD showed more deterioration at the trabecular region. This was corroborated by plasma osteocalcin and carboxy-terminal collagen crosslinks (CTx) levels confirming greater loss in males (about 20 %;P< 0·01). In both sexes cortical bone parameters and strength remained unchanged after 10 weeks of HFD treatment. The direct effect of the HFD on bone at the messenger RNA level in progenitor cells isolated from femoral bone marrow was a significantly increased expression of adipogenic marker genesv.osteogenic genes. Overall, the present data indicate that obesity induced by a HFD aggravates bone loss in the cancellous bone compartment, with a greater loss in males than females, although 10 weeks of HFD treatment did not alter cortical bone mass and strength in both males and females.
Modelling inter-human transmission dynamics of Chagas disease: analysis and application
Authors: FABRIZIO M. C. , SCHWEIGMANN N. J. , BARTOLONI N. J.
Published: February 2014

Transmission ofTrypanosoma cruzi, the causal agent of Chagas disease, has expanded from rural endemic to urban areas due to migration. This so-calledurban Chagasis an emerging health problem in American, European, Australian and Japanese cities. We present a mathematical model to analyse the dynamics of urban Chagas to better understand its epidemiology. The model considers the three clinical stages of the disease and the main routes of inter-human transmission. To overcome the complexities of the infection dynamics, the next-generation matrix method was developed. We deduced expressions which allowed estimating the number of new infections generated by an infected individual through each transmission route at each disease stage, the basic reproduction number and the number of individuals at each disease stage at the outbreak of the infection. The analysis was applied to Buenos Aires city (Argentina). We estimated that 94% of the new infections are generated by individuals in the chronic indeterminate stage. When migration was not considered, the infection disappeared slowly andR0 = 0·079, whereas when migration was considered, the number of individuals in each stage of the infection tended to stabilize. The expressions can be used to estimate different numbers of infected individuals in any place where only inter-human transmission is possible.