bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skeletal muscle dysfunction in the db/db mouse model of type 2 diabetes
Authors: Bayley Jeppe Seamus , Pedersen Thomas Holm , Nielsen Ole Bækgaard 
Published: February 2016

ABSTRACTIntroductionIn this study we examined the mechanisms of motor dysfunction in type 2 diabetes.MethodsContractile force was measured in isolated nerve–muscle preparations of db/db mice using various protocols for electrical stimulation. Sarcoplasmic reticulum Ca2+ adenosine triphosphatase protein (SERCA) was quantified by comparing Ca2+‐dependent and non‐specific phosphorylation.ResultsCompared with controls, the muscle–nerve preparations of db/db mice displayed muscle atrophy, reduced axonal excitability, and force deficit when stimulated via the nerve. Muscle relaxation after contraction was slowed, and SERCA content was reduced. In contrast, the sensitivity of the neuromuscular junction to tubocurarine and muscle fiber excitability were not affected.ConclusionsThe force deficit in db/db muscles was caused by atrophy and failure of neuromuscular signal transmission related to motor nerve axonal dysfunction. The slowed relaxation rate generally observed in diabetic muscles can, to a large extent, be explained by decreased SERCA pump content. Muscle Nerve 54: 460–468, 2016
In vivo observation of quadrupolar splitting in 39K magnetic resonance spectroscopy of human muscle tissue
Authors: Rösler M. B. , Nagel A. M. , Umathum R. , Bachert P. , Benkhedah N. 
Published: February 2016

The purpose of this work was to explore the origin of oscillations of the T*2 decay curve of 39K observed in studies of 39K magnetic resonance imaging of the human thigh. In addition to their magnetic dipole moment, spin‐3/2 nuclei possess an electric quadrupole moment. Its interaction with non‐vanishing electrical field gradients leads to oscillations in the free induction decay and to splitting of the resonance.All measurements were performed on a 7T whole‐body MRI scanner (MAGNETOM 7T, Siemens AG, Erlangen, Germany) with customer‐built coils. According to the theory of quadrupolar splitting, a model with three Lorentzian‐shaped peaks is appropriate for 39K NMR spectra of the thigh and calf. The frequency shifts of the satellites depend on the angle between the calf and the static magnetic field. When the leg is oriented parallel to the static magnetic field, the satellites are shifted by about 200 Hz. In the thigh, rank‐2 double quantum coherences arising from anisotropic quadrupolar interaction are observed by double‐quantum filtration with magic‐angle excitation. In addition to the spectra, an image of the thigh with a nominal resolution of (16 × 16 × 32) mm3 was acquired with this filtering technique in 1:17 h.From the line width of the resonances, 39K transverse relaxation time constants T*2, fast = (0.51 ± 0.01) ms and T*2, slow = (6.21 ± 0.05) ms for the head were determined. In the thigh, the left and right satellite, both corresponding to the short component of the transverse relaxation time constant, take the following values: T*2, fast = (1.56 ± 0.03) ms and T*2, fast = (1.42 ± 0.03) ms. The centre line, which corresponds to the slow component, is T*2, slow = (9.67 ± 0.04) ms. The acquisition time of the spectra was approximately 10 min. Our results agree well with a non‐vanishing electrical field gradient interacting with 39K nuclei in the intracellular space of muscle tissue. Copyright © 2016 John Wiley & Sons, Ltd.
A Green's discrete transformation meshfree method for simulating transient diffusion problems
Authors: Mai Weijie , Soghrati Soheil , Buchheit Rudolph G. 
Published: February 2016

SummaryThis manuscript presents the formulation and application of the Green's discrete transformation method (GDTM) for the meshfree simulation of transient diffusion problems, including those with moving boundaries. The GDTM implements a linear combination of time‐dependent Green's basis functions defined on a set of source points to approximate the field in the form of a solution series. A discrete transformation is implemented to evaluate unknown coefficients of this series, which eliminates the need to use time integration schemes. We will study the optimal number and location of the GDTM source points that yield the highest level of accuracy, while maintaining a manageable condition number for the resulting linear system of equations. The optimal values of these parameters, which are inherently independent of the domain geometry, are determined such that the basis functions have appropriate features for approximating the field. A comprehensive convergence study is presented to show the precision and convergence rate of the GDTM for modeling various diffusion problems. We also demonstrate the application of this method for simulating three diffusion problems with complex and evolving morphologies: heat transfer in a turbine blade, thermal response of a porous material, and localized (pitting) corrosion in stainless steel. Copyright © 2016 John Wiley & Sons, Ltd.
Computational Studies on Nitro, Nitramino, and Dinitramino Derivatives of 1‐Aminoazadiboridine as High Energetic Material
Authors: Gupta Satyendra , Sengupta Soumitra K. , Singh Hari Ji 
Published: February 2016

AbstractComputational studies were performed to determine the thermodynamic and explosive characteristics of high energy materials formed by placing explosophores such as nitro (−NO2), nitramino (−NHNO2), and dinitramino (−N(NO2)2) groups on 1‐aminoazadiboridine. G3 level calculations were made to determine the gas phase heat of formation of the designed species. In addition to the above, condensed phase heat of formation was also determined by evaluating the sublimation enthalpy. Crystal densities of title compounds were predicted with the help of a wave function analysis (WFA) program and were found to be in the range of 1.55–1.83 g cm−3. Bond dissociation energies of various possible bond rupture routes of the designed molecules were calculated at DFT‐B3LYP/6‐311G(d,p) level and attempt was made to identify the trigger linkage. Impact sensitivity was evaluated theoretically by employing a method based on statistical parameters determined from electrostatic potential data. Results show that the designed molecules are highly energetic and their corresponding detonation properties place them in the category of safe and high performance explosive materials.
Classification of proteins with shared motifs and internal repeats in the ECOD database
Authors: Schaeffer R. Dustin , Kinch Lisa N. , Liao Yuxing , Grishin Nick V. 
Published: February 2016

AbstractProteins and their domains evolve by a set of events commonly including the duplication and divergence of small motifs. The presence of short repetitive regions in domains has generally constituted a difficult case for structural domain classifications and their hierarchies. We developed the Evolutionary Classification Of protein Domains (ECOD) in part to implement a new schema for the classification of these types of proteins. Here we document the ways in which ECOD classifies proteins with small internal repeats, widespread functional motifs, and assemblies of small domain‐like fragments in its evolutionary schema. We illustrate the ways in which the structural genomics project impacted the classification and characterization of new structural domains and sequence families over the decade.
Iterative design of emetine‐based prodrug targeting fibroblast activation protein (FAP) and dipeptidyl peptidase IV DPPIV using a tandem enzymatic activation strategy
Authors: Akinboye Emmanuel S. , Brennen W. Nathaniel , Rosen D. Marc , Bakare Oladapo , Denmeade Samuel R. 
Published: February 2016

BACKGROUNDThere is an urgent need to develop new agents for treating metastatic prostate cancer to overcome multiple drug resistance to the current standard targeted cancer therapy. Emetine is a highly cytotoxic natural product protein synthesis inhibitor, which is toxic to all cell types. Its cytotoxicity can be blocked by derivatizing its N‐2′ position. Thus emetine can be selectively delivered to cancer cells in the region of metastatic cancer as a prodrug that will be activated by an enzyme selectively overexpressed within the metastatic tumor microenvironment. In this work, we convert emetine to a prodrug activatable by the fibroblast activation protein (FAP), a serine protease overexpressed by the carcinoma associated fibroblasts.METHODBy using an iterative structure‐activity relationship strategy, several peptidyl emetine prodrug analogs (1–11) were synthesized by chemical derivatization of emetine at its N‐2′ position and tested for in‐vitro activation by FAP. The lead prodrug 11 is made up of a DPPIV activatable prodrug precursor 10 (Ala‐Pro‐PABC‐Emetine) coupled to FAP substrate (Ala‐Ser‐Gly‐Pro‐Ala‐Gly‐Pro). Activation assays of the prodrugs were performed in purified FAP, DPPIV, FBS, and human serum and were analyzed by LCMS. In vitro cytotoxicity assays of these prodrugs are carried out in prostate (LNCaP, PC3) and breast (MCF7 and MDA‐MB‐231) cancer cell lines. The prodrugs are also tested in normal immortalized human prostatic epithelial cell line (PrEC).RESULTSThe lead FAP activated emetine prodrug 11 is activated to emetine in tandem by FAP and DPPIV in about 70% conversion within 24 hr. In prostate and breast cancer cell lines treated with prodrug 11, it is found to be equipotent with emetine in the presence of FAP and DPPIV. However, in the PrEC cell line grown in serum free media, prodrug 11 is more than 200‐fold less cytotoxic than emetine in the absence of FAP and DPPIV.CONCLUSIONThis FAP activated prodrug of cytotoxic agent emetine further shows the crucial role of the N‐2′ position of emetine in controlling its cytotoxicity. Significantly reduced toxicity observed in the PrEC cell line in the absence of FAP and DPPIV shows that prodrug 11 could be systemically delivered to regions of metastatic prostate cancer or other solid tumor for activation by cancer selective enzymes within the cancer microenvironment, such as FAP that is overexpressed by the carcinoma‐associated fibroblasts. The two‐step tandem enzymatic activation of prodrug 11 by FAP and DPPIV is a strategy for overcoming steric hindrance. Prostate 76:703–714, 2016. © 2016 Wiley Periodicals, Inc.
Allelobiosis in the interference of allelopathic wheat with weeds
Authors: Li Yong‐Hua , Xia Zhi‐Chao , Kong Chui‐Hua 
Published: February 2016

AbstractBACKGROUNDPlants may chemically affect the performance of neighbouring plants through allelopathy, allelobiosis or both. In spite of increasing knowledge about allelobiosis, defined as the signalling interactions mediated by non‐toxic chemicals involved in plant–plant interactions, the phenomenon has received relatively little attention in the scientific literature. This study examined the role of allelobiosis in the interference of allelopathic wheat with weeds.RESULTSAllelopathic wheat inhibited the growth of five weed species tested, and the allelochemical (2,4‐dihydroxy‐7‐methoxy‐1,4‐benzoxazin‐3‐one) production of wheat was elicited in the presence of these weeds, even with root segregation. The inhibition and allelochemical levels varied greatly with the mixed species density. Increased inhibition and allelochemical levels occurred at low and medium densities but declined at high densities. All the root exudates and their components of jasmonic acid and salicylic acid from five weeds stimulated allelochemical production. Furthermore, jasmonic acid and salicylic acid were found in plants, root exudates and rhizosphere soils, regardless of weed species, indicating their participation in the signalling interactions defined as allelobiosis.CONCLUSIONThrough root‐secreted chemical signals, allelopathic wheat can detect competing weeds and respond by increased allelochemical levels to inhibit them, providing an advantage for its own growth. Allelopathy and allelobiosis are two probably inseparable processes that occur together in wheat–weed chemical interactions. © 2016 Society of Chemical Industry
EPCS: an efficient and privacy‐preserving classification service query framework for SVM
Authors: Zhu Hui , Liu Xiaoxia , Lu Rongxing , Li Hui 
Published: February 2016

AbstractSupport vector machine (SVM) classification, which can handle large data sets in high dimensional spaces, has been widely applied in numerous settings nowadays, such as genetic match, spam detection, and financial prediction. However, because of the data's sensitivity and classifiers' confidentiality, how to provide a privacy‐preserving SVM classification has attracted considerable interest recently. Aiming at these privacy challenges, in this paper, we present an efficient and privacy‐preserving classification service query framework, named EPCS, for the linear kernel SVM classifier. Specifically, based on lightweight multiparty random masking and polynomial aggregation techniques, EPCS preserves the privacy of users' data and SVM classifier efficiently during the process of user query. Through detailed security analysis, we show that EPCS can resist various security threats. In addition, we implement EPCS in Java and evaluate EPCS over a smart phone and a PC, and extensive simulation results demonstrate that the EPCS framework can indeed achieve high efficiency and effectiveness in SVM classification. Copyright © 2016 John Wiley & Sons, Ltd.
Structurally Different Calcium(II) Complexes with 5‐Substituted Tetrazole Ligands
Authors: Liu Qiao , Zhao Li Yang , Lu Yi Ming , Yue Qiu Yan , Zhang Fei Fei , Wei Bo , Li Qiao Yun , Yang Gao Wen 
Published: February 2016

AbstractThree different tetrazole‐carboxylate ligands, Hpymtza, Hpytza, and H2dtzeda were chosen to be reacted with Ca(NO3)2·4H2O, resulting in the formation of three coordination compounds, [Ca(pymtza)2(H2O)4] (1), [Ca(pytza)2(H2O)2] (2), and [Ca(dtzeda)(H2O)2] (3) [Hpymtza = 5‐(2‐pyrimidyl)tetrazole‐1‐acetic acid, Hpytza = 5‐(3‐pyridyl)tetrazole‐2‐acetic acid, and H2dtzeda = 1, 2‐bis(tetrazol‐5‐yl)ethane‐N1, N1′‐diacetic acid]. X‐ray diffraction analysis revealed that compound 1 displays a mononuclear structure, compound 2 is a one dimensional zigzag chain structure, whereas 3 shows a three‐dimensional structure. The structures were controlled by not only the different substituents of the tetrazolyl ring, but also the complementary hydrogen bonds. Furthermore, the luminescence properties of compounds 1–3 were investigated at room temperature in the solid state. These emissions can be tentatively attributed to the ligand centered emission.
Reward functions of the basal ganglia
Authors: Schultz Wolfram 
Published: February 2016

Abstract
Besides their fundamental movement function evidenced by Parkinsonian deficits, the basal ganglia are involved in processing closely linked non-motor, cognitive and reward information. This review describes the reward functions of three brain structures that are major components of the basal ganglia or are closely associated with the basal ganglia, namely midbrain dopamine neurons, pedunculopontine nucleus, and striatum (caudate nucleus, putamen, nucleus accumbens). Rewards are involved in learning (positive reinforcement), approach behavior, economic choices and positive emotions. The response of dopamine neurons to rewards consists of an early detection component and a subsequent reward component that reflects a prediction error in economic utility, but is unrelated to movement. Dopamine activations to non-rewarded or aversive stimuli reflect physical impact, but not punishment. Neurons in pedunculopontine nucleus project their axons to dopamine neurons and process sensory stimuli, movements and rewards and reward-predicting stimuli without coding outright reward prediction errors. Neurons in striatum, besides their pronounced movement relationships, process rewards irrespective of sensory and motor aspects, integrate reward information into movement activity, code the reward value of individual actions, change their reward-related activity during learning, and code own reward in social situations depending on whose action produces the reward. These data demonstrate a variety of well-characterized reward processes in specific basal ganglia nuclei consistent with an important function in non-motor aspects of motivated behavior.
Computational design of an automotive twist beam
Authors: Aalae Benki , Abderrahmane Habbal , Gael Mathis 
Published: February 2016

Abstract
In recent years, the automotive industry has known a remarkable development in order to satisfy the customer requirements. In this paper, we will study one of the components of the automotive which is the twist beam. The study is focused on the multicriteria design of the automotive twist beam undergoing linear elastic deformation (Hooke's law). Indeed, for the design of this automotive part, there are some criteria to be considered as the rigidity (stiffness) and the resistance to fatigue. Those two criteria are known to be conflicting, therefore, our aim is to identify the Pareto front of this problem. To do this, we used a Normal Boundary Intersection (NBI) algorithm coupling with a radial basis function (RBF) metamodel in order to reduce the high calculation time needed for solving the multicriteria design problem. Otherwise, we used the free form deformation (FFD) technique for the generation of the 3D shapes of the automotive part studied during the optimization process.
Highlights We model the automotive twist beam. We developed an algorithm to solve multicriteria optimization problem. We solve our industrial problem with our developed algorithm. New profiles of the twist beam are proposed.
Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines
Authors: Lin Zu‐Yau , Kuo Chao‐Hung , Wu Deng‐Chyang , Chuang Wan‐Long 
Published: February 2016

AbstractColchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer effects on gastric cancer cells, and its possible anticancer mechanisms. Two human gastric cancer cell lines (i.e., AGS and NCI‐N87) were investigated by proliferative assay, microarray, quantitative reverse transcriptase‐polymerase chain reaction, and a nude mice study using clinically acceptable colchicine concentrations (2 ng/mL and 6 ng/mL for in vitro tests and 0.07 mg colchicine/kg/d for in vivo tests). Our results showed that colchicine had the same inhibitory effects on the proliferation of both cell lines. The antiproliferative effects of colchicine on both cell lines were achieved only at the concentration of 6 ng/mL (p < 0.0001). In both cell lines, 18 genes were consistently upregulated and 10 genes were consistently downregulated by 6 ng/mL colchicine, compared with 2 ng/mL colchicine. Among these genes, only the upregulated DUSP1 gene may contribute to the antiproliferative effects of colchicine on gastric cancer cells. The nude mice (BALB/c‐nu) experiment showed that colchicine‐treated mice after 14 days of treatment had lower increased tumor volume ratios (p = 0.0199) and tumor growth rates (p = 0.024) than the control mice. In conclusion, colchicine has potential for the palliative treatment of gastric cancer. However, the anticancer effects are achieved only at high clinically acceptable colchicine concentrations. Monitoring the colchicine plasma concentration is mandatory if this drug is applied for the palliative treatment of gastric cancer.
Refining the Structure and Revisiting the Relevant Jurisdiction of Crimes against Humanity
Authors: Zysset Alain 
Published: February 2016

In this article, I test predominant normative approaches to CAH against the notion’s deployment in law. Embarking on this cross-disciplinary project is needed because those the predominant literature fail to address (or were just articulated before) the waves of cases brought before international criminal courts throughout the last decade. I start by examining how international criminal courts have specified the core elements of the definition and then assessifandhowthe predominant philosophical literature can account for it. I then argue that this legal-empirical inquiry leads to both refining the structure and revisiting the relevant jurisdiction of CAH.As far as structure is concerned, I distinguish a third but neglected element in the structure of CAH, which I identify as thepreparatory conditions of the crimes(the ‘PCs’). In relying on Joseph Raz’ concept of authority, I argue that reconstructing the PCs help to specify what it is about states that those crimes deeply pervert. While the PCs strikingly mirror the systematic and pre-emptive role of the state, those patterns are established to massively persecute, terrorize and finally odiously attack. As far as jurisdiction is concerned, I infer that the agent of CAH and the state in which those crimes occur become ‘answerable’ to the normative community of responsible states (following Anthony Duff’s accountability model). By establishing international trials, this normative community does justice not only to the victims by proving the crimes but also to the perpetrators by treating them as responsible members.
Prevalence of qacA/B Genes and Mupirocin Resistance Among Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates in the Setting of Chlorhexidine Bathing Without Mupirocin
Authors: Warren David K. , Prager Martin , Munigala Satish , Wallace Meghan A. , Kennedy Colleen R. , Bommarito Kerry M. , Mazuski John E. , Burnham Carey-Ann D. 
Published: February 2016

OBJECTIVEWe aimed to determine the frequency of qacA/B chlorhexidine tolerance genes and high-level mupirocin resistance among MRSA isolates before and after the introduction of a chlorhexidine (CHG) daily bathing intervention in a surgical intensive care unit (SICU).DESIGNRetrospective cohort study (2005–2012)SETTINGA large tertiary-care centerPATIENTSPatients admitted to SICU who had MRSA surveillance cultures of the anterior naresMETHODSA random sample of banked MRSA anterior nares isolates recovered during (2005) and after (2006–2012) implementation of a daily CHG bathing protocol was examined for qacA/B genes and high-level mupirocin resistance. Staphylococcal cassette chromosome mec (SCCmec) typing was also performed.RESULTSOf the 504 randomly selected isolates (63 per year), 36 (7.1%) were qacA/B positive (+) and 35 (6.9%) were mupirocin resistant. Of these, 184 (36.5%) isolates were SCCmec type IV. There was a significant trend for increasing qacA/B (P=.02; highest prevalence, 16.9% in 2009 and 2010) and SCCmec type IV (P<.001; highest prevalence, 52.4% in 2012) during the study period. qacA/B(+) MRSA isolates were more likely to be mupirocin resistant (9 of 36 [25%] qacA/B(+) vs 26 of 468 [5.6%] qacA/B(−); P=.003).CONCLUSIONSA long-term, daily CHG bathing protocol was associated with a change in the frequency of qacA/B genes in MRSA isolates recovered from the anterior nares over an 8-year period. This change in the frequency of qacA/B genes is most likely due to patients in those years being exposed in prior admissions. Future studies need to further evaluate the implications of universal CHG daily bathing on MRSA qacA/B genes among hospitalized patients.Infect Control Hosp Epidemiol 2016;37:590–597