bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of highly selective sigma‐1 receptor antagonist CM304 using liquid chromatography tandem mass spectrometry and its application to a pre‐clinical pharmacokinetic study
Authors: Avery Bonnie A. , Vuppala Pradeep K. , Jamalapuram Seshulatha , Sharma Abhisheak , Mesangeau Christophe , Chin Frederick T. , McCurdy Christopher R. 
Published: December 2016

An ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) method was developed and validated for quantification of CM304, a novel and highly selective sigma‐1 receptor antagonist that has recently entered into human clinical trials. A structural analogue of CM304, SN56, was used as the internal standard (IS). Chromatographic separation was achieved on an Acquity UPLC™ BEH C18 (1.7 μm, 2.1 mm × 50 mm) column using a mobile phase [water:methanol (0.1%v/v formic acid; 50:50, %v/v)] at a flow rate of 0.2 mL/min. Mass spectrometric detection was performed in the positive ionization mode with multiple reaction monitoring (MRM) using m/z transitions of 337 > 238 for CM304 and 319 > 220 for the IS. The method was found to be linear and reproducible with a regression coefficient consistently >0.99 for the calibration range of 3 to 3000 ng/mL. The extraction recovery ranged from 91.5 to 98.4% from spiked (7.5, 300 and 2526 ng/mL) plasma quality control samples. The precision (%RSD; 1.1 to 2.9%) and accuracy (%RE; −1.9 to 1.8%) were within acceptable limit. The validated method was successfully applied to a single dose oral and intravenous (I.V.) pharmacokinetic study of CM304 in rats. Following I.V. administration, the compound exhibited adequate exposure along with high extravascular distribution and insignificant amount of extra hepatic metabolism. Copyright © 2016 John Wiley & Sons, Ltd.
Study design and parameter estimability for spatial and temporal ecological models
Authors: Peacock Stephanie Jane , Krkošek Martin , Lewis Mark Alun , Lele Subhash 
Published: December 2016

AbstractThe statistical tools available to ecologists are becoming increasingly sophisticated, allowing more complex, mechanistic models to be fit to ecological data. Such models have the potential to provide new insights into the processes underlying ecological patterns, but the inferences made are limited by the information in the data. Statistical nonestimability of model parameters due to insufficient information in the data is a problem too‐often ignored by ecologists employing complex models. Here, we show how a new statistical computing method called data cloning can be used to inform study design by assessing the estimability of parameters under different spatial and temporal scales of sampling. A case study of parasite transmission from farmed to wild salmon highlights that assessing the estimability of ecologically relevant parameters should be a key step when designing studies in which fitting complex mechanistic models is the end goal.
Genome Compositional Organization in Gars Shows More Similarities to Mammals than to Other Ray‐Finned Fish
Authors: Symonová Radka , Majtánová Zuzana , Arias‐Rodriguez Lenin , Mořkovský Libor , Kořínková Tereza , Cavin Lionel , Pokorná Martina Johnson , Doležálková Marie , Flajšhans Martin , Normandeau Eric , Ráb Petr , Meyer Axel , Bernatchez Louis 
Published: December 2016

ABSTRACTGenomic GC content can vary locally, and GC‐rich regions are usually associated with increased DNA thermostability in thermophilic prokaryotes and warm‐blooded eukaryotes. Among vertebrates, fish and amphibians appeared to possess a distinctly less heterogeneous AT/GC organization in their genomes, whereas cytogenetically detectable GC heterogeneity has so far only been documented in mammals and birds. The subject of our study is the gar, an ancient “living fossil” of a basal ray‐finned fish lineage, known from the Cretaceous period. We carried out cytogenomic analysis in two gar genera (Atractosteus and Lepisosteus) uncovering a GC chromosomal pattern uncharacteristic for fish. Bioinformatic analysis of the spotted gar (Lepisosteus oculatus) confirmed a GC compartmentalization on GC profiles of linkage groups. This indicates a rather mammalian mode of compositional organization on gar chromosomes. Gars are thus the only analyzed extant ray‐finned fishes with a GC compartmentalized genome. Since gars are cold‐blooded anamniotes, our results contradict the generally accepted hypothesis that the phylogenomic onset of GC compartmentalization occurred near the origin of amniotes. Ecophysiological findings of other authors indicate a metabolic similarity of gars with mammals. We hypothesize that gars might have undergone convergent evolution with the tetrapod lineages leading to mammals on both metabolic and genomic levels. Their metabolic adaptations might have left footprints in their compositional genome evolution, as proposed by the metabolic rate hypothesis. The genome organization described here in gars sheds new light on the compositional genome evolution in vertebrates generally and contributes to better understanding of the complexities of the mechanisms involved in this process.
Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke
Authors: Zhou Yi‐Jiang , Yin Rui‐Xing , Hong Shao‐Cai , Yang Qian , Cao Xiao‐Li , Chen Wu‐Xian 
Published: December 2016

AbstractBackgroundHepatocyte nuclear factor‐1α gene (HNF1A) single nucleotide polymorphisms (SNPs) have been associated with serum lipid traits in several previous genome‐wide association studies. However, little is known about such associations in the Chinese populations. The present study aimed to determine the association of the HNF1A rs1169288, rs2259820, rs2464196 and rs2650000 SNPs and serum lipid traits, the risk of coronary artery disease (CAD) and ischemic stroke (IS).MethodsThe genotypes of the four SNPs in 562 CAD and 521 IS patients, as well as 594 healthy controls, were detected using the Snapshot technology.ResultsThe genotype and allele distribution of the four SNPs was not different between controls and CAD or IS patients (p > 0.05 for all). rs1169288, rs2259820 and rs2464196 SNPs were significantly associated with serum lipid levels in both controls and CAD patients (p < 0.004–0.009). rs2259820 and rs2464196 SNPs were significantly associated with a lower risk of CAD [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.44–0.91, p = 0.015 and OR =0.62, 95% CI = 0.43–0.89, p = 0.010, respectively]. Significant linkage disequilibrium was noted among the four SNPs (r2 > 0.5, D′ > 0.8). The haplotype of rs1169288A‐rs2259820C‐rs2464196G‐rs2650000A was associated with an increased risk of CAD (OR =1.95, 95% CI: 1.13–3.37, p = 0.015). Interactions of SNP–SNP (rs1169288–rs2464196–rs2650000) and haplotype–environment on the risk of CAD (A‐C‐G‐A–smoking) or IS (A‐C‐G‐A–sex and A‐T‐A‐C–alcohol consumption) were also observed among these SNPs.ConclusionsThese findings suggest that the HNF1A polymorphisms may be the genetic risk factors for CAD and IS.
Improving the Thermal Properties of Poly(2,5‐furandicarboxylate)s Using Cyclohexylene Moieties: A Comparative Study
Authors: Matos Marina , Sousa Andreia F. , Silvestre Armando J. D. 
Published: December 2016

The search for new polymers from renewable origin is a sparkling field in polymer chemistry, especially those having promising properties, for example, in terms of their thermal performance. In this vein, in this study, an original renewable 2,5‐furandicarboxylic acid‐based cycloaliphatic homopolyester, poly(1,4‐cyclohexylene 2,5‐furandicarboxylate) (PCdF), is synthesized from dimethyl‐2,5‐furandicarboxylate and 1,4‐cyclohexanediol. Poly(1,4‐cyclohexanedimethylene 2,5‐furandicarboxylate) is also prepared for comparison purposes, since it is the direct renewable substitute of poly(1,4‐cyclohexanedimethylene terephthalate) and they are structurally related. The resulting homopolyesters are characterized in detail by using attenuated total reflectance Fourier transform infrared, 1H, 13C and 2D NMR, X‐ray and elemental analysis, and thermal properties are assessed by thermogravimetric analysis, differential scanning calorimetry, and dynamic mechanical thermal analysis. PCdF shows to have a semicrystalline character, exhibiting an extremely high glass transition temperature around 175 °C. Moreover, this polyester also shows to be a high thermally stable material with a degradation temperature of 380.0 °C.
image
Targeted metabolomics reveals differences in the extended postprandial plasma metabolome of healthy subjects after intake of whole‐grain rye porridges versus refined wheat bread
Authors: Shi Lin , Brunius Carl , Lindelöf Magnus , Shameh Souad Abou , Wu Huaxing , Lee Isabella , Landberg Rikard , Moazzami Ali A. 
Published: December 2016

ScopeWe previously found that whole‐grain (WG) rye porridges suppressed appetite and improved glucose metabolism. This study aimed to investigate potential plasma metabolites that may be related to differences in those appetite and glucose responses.Methods and resultsTwenty‐one health subjects consumed six isocaloric breakfasts in a randomized cross‐over study. Plain WG rye porridges (40 and 55 g), rye porridge enriched with different inulin: gluten proportions (9:3 g; 6:6 g; 3:9 g), and a 55 g refined wheat bread (control) were served as part of complete breakfast, followed by a standardized lunch. NMR metabolomics assessed 36 plasma metabolites and short chain fatty acids were measured by GC‐MS from baseline up to 8 h. Pre‐lunch plasma essential amino acids reflected protein composition and post‐lunch plasma short chain fatty acids varied with fiber content in breakfasts. No correlations were observed between measured metabolites and glucose, insulin, or appetite responses.ConclusionsDifferences in protein and fiber contents in breakfasts altered postprandial plasma amino acids and short chain fatty acids, respectively, but were unrelated to appetite and glucose responses. Further studies are warrant to identify the underlying mechanisms for the beneficial effects on appetite and second meal glucose responses after rye‐based foods.
Effects of low energy shock wave therapy on inflammatory moleculars, bladder pain, and bladder function in a rat cystitis model
Authors: Wang Hung‐Jen , Lee Wei‐Chia , Tyagi Pradeep , Huang Chao‐Cheng , Chuang Yao‐Chi 
Published: December 2016

AimsLow energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti‐inflammatory effects. We examined the effects of LESW on the expression of inflammatory molecules, pain behavior, and bladder function in a rat cystitis model.MethodsControl and experimental animals were injected with saline or cyclophosphamide (CYP; 75 mg/kg intraperitoneally) on day 1 and 4. After lower midline incision, the bladders were exposed to LESW (300 pulses, 0.12 mJ/mm2) or sham operation on day 2. In study 1 (N = 12, 4 for each group), the nociceptive effects of CYP were evaluated for 30 min by behavioral assessment on day 4 one hour after CYP injection. In study 2 (N = 21, 7 for each group), continuous cystometry (CMG) was performed on day 8. The bladder was harvested after behavioral assessment or CMG for histology and Western blotting.ResultsCYP‐induced upregulation of COX2 and IL6 expression, caused pain behavior (eye closing and hypolocomotion), and bladder inflammation was noted on days 4 and 8 along with bladder hyperactivity. LESW treatment reduced pain behavior and downregulated the NGF expression (33.3%, P < 0.05) on day 4 and IL6 (40.9%, P < 0.05). LESW treatment suppressed bladder overactivity (intercontraction interval 77.8% increase, P < 0.05) by decreasing inflammation and COX2 (38.6%, P < 0.05) expression and NGF expression (25.2%, P = 0.0812).ConclusionsCYP‐induced bladder pain, inflammation, and overactivity involves activation of IL6, NGF, and COX2 expression. These changes are suppressed by LESW, indicating it as a potential candidate for relieving bladder inflammatory conditions and overactivity.
Molecular insights into tumour metastasis: tracing the dominant events
Authors: Jin Ke , Li Tong , van Dam Hans , Zhou Fangfang , Zhang Long 
Published: December 2016

AbstractMetastasis of malignant cells to vital organs remains the major cause of mortality in many types of cancers. The tumour invasion–metastasis cascade is a stepwise and multistage process whereby tumour cells disseminate from primary sites and spread to colonize distant sites through the systemic haematogenous or lymphatic circulations. The general steps of metastasis may be similar in almost all tumour types, but metastasis to different tissues seems to require distinct sets of regulators and/or an ‘educated’ microenvironment which may facilitate the infiltration and colonization of tumour cells to specific tissues. Moreover, interactions of tumour cells with stromal cells, endothelial cells, and immune cells that they encounter will also aid them to gain survival advantages, evade immune surveillance, and adapt to the new host microenvironment. Due to the high correlation between tumour metastasis and survival rate of patients, a deeper understanding of the molecular participants and processes involved in metastasis could pave the way towards novel, more effective and targeted approaches to prevent and treat tumour metastasis. In this review, we provide an update on the regulation networks orchestrated by the dominant regulators of different stages throughout the metastatic process including, but not limited to, epithelial–mesenchymal transition in local invasion, resistance to anoikis during migration, and colonization of different distant sites. We also put forward some suggestions and problems concerning the treatment of tumour metastasis that should be solved and/or improved for better therapies in the near future. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Nuclear inclusion bodies of mutant and wild‐type p53 in cancer: a hallmark of p53 inactivation and proteostasis remodelling by p53 aggregation
Authors: De Smet Frederik , Saiz Rubio Mirian , Hompes Daphne , Naus Evelyne , De Baets Greet , Langenberg Tobias , Hipp Mark S , Houben Bert , Claes Filip , Charbonneau Sarah , Delgado Blanco Javier , Plaisance Stephane , Ramkissoon Shakti , Ramkissoon Lori , Simons Colinda , van den Brandt Piet , Weijenberg Matty , Van England Manon , Lambrechts Sandrina , Amant Frederic , D'Hoore André , Ligon Keith L , Sagaert Xavier , Schymkowitz Joost , Rousseau Frederic 
Published: December 2016

AbstractAlthough p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact in cancer remains largely unknown. Here, we extensively screened for p53 aggregation phenotypes in tumour biopsies, and identified nuclear inclusion bodies (nIBs) of transcriptionally inactive mutant or wild‐type p53 as the most frequent aggregation‐like phenotype across six different cancer types. p53‐positive nIBs co‐stained with nuclear aggregation markers, and shared molecular hallmarks of nIBs commonly found in neurodegenerative disorders. In cell culture, tumour‐associated stress was a strong inducer of p53 aggregation and nIB formation. This was most prominent for mutant p53, but could also be observed in wild‐type p53 cell lines, for which nIB formation correlated with the loss of p53's transcriptional activity. Importantly, protein aggregation also fuelled the dysregulation of the proteostasis network in the tumour cell by inducing a hyperactivated, oncogenic heat‐shock response, to which tumours are commonly addicted, and by overloading the proteasomal degradation system, an observation that was most pronounced for structurally destabilized mutant p53. Patients showing tumours with p53‐positive nIBs suffered from a poor clinical outcome, similar to those with loss of p53 expression, and tumour biopsies showed a differential proteostatic expression profile associated with p53‐positive nIBs. p53‐positive nIBs therefore highlight a malignant state of the tumour that results from the interplay between (1) the functional inactivation of p53 through mutation and/or aggregation, and (2) microenvironmental stress, a combination that catalyses proteostatic dysregulation. This study highlights several unexpected clinical, biological and therapeutically unexplored parallels between cancer and neurodegeneration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Investigating subsurface damages in semiconductor–insulator–semiconductor solar cells with THz spectroscopy
Authors: Blumröder Ulrike , Hempel Hannes , Füchsel Kevin , Hoyer Patrick , Bingel Astrid , Eichberger Rainer , Unold Thomas , Nolte Stefan 
Published: December 2016

AbstractThe influence of near‐surface crystal damage on carrier dynamics in silicon has been investigated with optical‐pump THz‐probe and THz emission studies. The surface damage is caused by a plasma process used for the fabrication of the ultrathin insulator within semiconductor–insulator–semiconductor (SIS) solar cells. The ion bombardment during the plasma process introduces a highly damaged subsurface region. Furthermore, the integration of positive interface charges leads to the formation of a depletion region that can be detected via the emitted THz radiation. The results are compared with classic I–U‐characterization demonstrating that THz spectroscopy can be used as a supplementary tool for the investigation of process‐induced surface damages.
Analysis of soluble components in coals and interpretations for the complex mass spectra
Authors: Fan Xing , Yu Ya‐Ru , Xia Jun‐Liu , Zhao Yun‐Peng , Cao Jing‐Pei , Lu Yao , Yue Xiao‐Ming , Zhu Teng‐Gao , Wei Xian‐Yong , Lu Jin‐Li 
Published: December 2016

RationaleThe deduction of useful information from the mass spectra of a complex mixture like coals remains difficult, which limits the clean and efficient utilization of coals. It is necessary to explore the data interpretation methods for mass spectra and visualize the analytical data of coals for industrial utilization such as feedstock selection.MethodsCoal sample and methanol were mixed and heated to 310 °C and kept at that temperature for 2 h. The solvent was under supercritical state at 310 °C and the solubility for the solid mixture increased. Soluble products from thermal dissolution of two Chinese coals were analyzed by high‐performance liquid chromatography/atmospheric pressure chemical ionization orbitrap mass spectrometry.ResultsThe iso‐abundance plot for molecules in coals was upgraded to display the distributions of isomers which are indicated as concentric circles or triangles with the same carbon number and value of double‐bond equivalent. The concentration ratio was introduced from economics to describe the content inequality of organic species within the same class of coal molecules.ConclusionsInterpretation methods for mass spectra visualize and simplify the understanding of complex components in coals for industrial utilization. Coals with a high concentration ratio for a specific class should take priority as a feedstock for chemicals and receive more attention. Copyright © 2016 John Wiley & Sons, Ltd.
Skew and heavy‐tail effects on firm performance
Authors: Makino Shige , Chan Christine M. 
Published: December 2016

Research summary: Most strategic management studies adopt an average‐centered view that uses the central tendency to explain between‐group variation in performance (i.e., performance differences between business units, firms, industries, and countries). In this study, we explain within‐group variation using a variance‐centered view that focuses on the peripheral characteristics of performance distributions as defined by skew and heavy tails (i.e., variance and kurtosis). Drawing on performance feedback theory, we hypothesize that successful firms tend to develop a positive skew in their performance distributions, which we call a “positive skew effect” in this study, and that heavy tails moderate this effect. Our analysis of the performance of a group of foreign affiliates provides general support for our hypotheses at both the firm and segment (industry and country) levels.Managerial summary: Managers of multi‐business firms use various approaches to improve the aggregate performance of their business units. Some expand the range of upper performance outliers (exploration) or reduce the range of lower outliers (downsizing); others improve the performance of current business units (exploitation). We find that firms with superior performance tend to have a balanced mix of the three approaches. We also find that segments (countries and industries) with higher mean performances provide environments that facilitate the entry of productive firms and the exit of unproductive firms and provide environments in which incumbents can further improve their performance by learning from others. We observe that successful firms and segments have a positive skew in their performance distributions, which we call a “positive skew effect.” Copyright © 2016 John Wiley & Sons, Ltd.
Negotiating with the future: incorporating imaginary future generations into negotiations
Authors: Kamijo Yoshio , Komiya Asuka , Mifune Nobuhiro , Saijo Tatsuyoshi 
Published: December 2016

Abstract
People to be born in the future have no direct influence on current affairs. Given the disconnect between people who are currently living and those who will inherit the planet left for them, individuals who are currently alive tend to be more oriented toward the present, posing a fundamental problem related to sustainability. In this study, we propose a new framework for reconciling the disconnect between the present and the future whereby some individuals in the current generation serve as an imaginary future generation that negotiates with individuals in the real-world present. Through a laboratory-controlled intergenerational sustainability dilemma game (ISDG), we show how the presence of negotiators for a future generation increases the benefits of future generations. More specifically, we found that when faced with members of an imaginary future generation, 60% of participants selected an option that promoted sustainability. In contrast, when the imaginary future generation was not salient, only 28% of participants chose the sustainable option.
Optimization of the Functional Characteristics of Cleaning Products Through Experimental Design
Authors: Ochoa Douglas Herlemann , Braga Jez Willian Batista , Machado Fabricio 
Published: December 2016

AbstractTo optimize a benchmark commercial dishwashing formulation, this paper presents a fractional factorial design procedure coupled with a mixture design in order to obtain a formulation with better properties and cost, as well as to provide an example of quick formula optimization that may also be useful for other cleaning and personal hygiene sectors. First, a fractional factorial design was performed to determine the significant effects for each response variable: viscosity, performance, foaming, and Krafft temperature. Then, a mixture design was used to determine the compositions that feature the best results for each property of interest. The determined compositions that meet the requirements with 90–95% confidence showed that improvements in the compositions can be adopted. It was possible to estimate compositions based on commercial formulations that meet the same cost per kilogram of product but with gains in detergency, foaming, and viscosity volume.