bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dihydrogen Splitting Using Dialkylsilylene‐Based Frustrated Lewis Pairs
Authors: Dong Zhaowen , Li Zhifang , Liu Xupeng , Yan Chenting , Wei Ningka , Kira Mitsuo , Müller Thomas 
Published: February 2017

AbstractIsolable dialkylsilylene 5 reacts with dihydrogen in the presence of a small amount of a conventional Lewis acid (BPh3, BEt3) or a base (PPh3, PEt3, NPh3, NEt3) at low temperatures in a hydrocarbon solvent, giving the corresponding dihydrosilane 10 in high yields. Both 5/Lewis acid and Lewis base/5 pairs work as a frustrated Lewis pair (FLP) to split dihydrogen, being in accord with the amphoteric nature of silylene 5.
Rare copy number variants in patients with congenital conotruncal heart defects
Authors: Xie Hongbo M. , Werner Petra , Stambolian Dwight , Bailey‐Wilson Joan E. , Hakonarson Hakon , White Peter S. , Taylor Deanne M. , Goldmuntz Elizabeth 
Published: February 2017

BackgroundPrevious studies using different cardiac phenotypes, technologies and designs suggest a burden of large, rare or de novo copy number variants (CNVs) in subjects with congenital heart defects. We sought to identify disease‐related CNVs, candidate genes, and functional pathways in a large number of cases with conotruncal and related defects that carried no known genetic syndrome.MethodsCases and control samples were divided into two cohorts and genotyped to assess each subject's CNV content. Analyses were performed to ascertain differences in overall CNV prevalence and to identify enrichment of specific genes and functional pathways in conotruncal cases relative to healthy controls.ResultsOnly findings present in both cohorts are presented. From 973 total conotruncal cases, a burden of rare CNVs was detected in both cohorts. Candidate genes from rare CNVs found in both cohorts were identified based on their association with cardiac development or disease, and/or their reported disruption in published studies. Functional and pathway analyses revealed significant enrichment of terms involved in either heart or early embryonic development.ConclusionOur study tested one of the largest cohorts specifically with cardiac conotruncal and related defects. These results confirm and extend previous findings that CNVs contribute to disease risk for congenital heart defects in general and conotruncal defects in particular. As disease heterogeneity renders identification of single recurrent genes or loci difficult, functional pathway and gene regulation network analyses appear to be more informative. Birth Defects Research 109:271–295, 2017. © 2017 Wiley Periodicals, Inc.
NDRG1 is important to maintain the integrity of airway epithelial barrier through claudin‐9 expression
Authors: Gon Yasuhiro , Maruoka Shuichiro , Kishi Hiroyuki , Kozu Yutaka , Kazumichi Kuroda , Nomura Yasuyuki , Takeshita Ikuko , Oshima Takeshi , Hashimoto Shu 
Published: February 2017

AbstractImpairment of epithelial barrier integrity caused by environmental triggers is associated with the pathogenesis of airway inflammation. Using human airway epithelial cells, we attempted to identify molecule(s) that promote airway epithelial barrier integrity. Microarray analyses were conducted using the Affimetrix human whole genome gene chip, and we identified the N‐myc downstream‐regulated gene 1 (NDRG1) gene, which was induced during the development of the epithelial cell barrier. Immunohistochemical analysis revealed strong NDRG1 expression in ciliated epithelial cells in nasal tissues sampled from patients with chronic rhinosinusitis (CRS), and the low expression of NDRG1 was observed in goblet cells or damaged epithelial cells. NDRG1 gene knockdown with its specific siRNA decreased the transepithelial electrical resistance and increased the dextran permeability. Immunocytochemistry revealed that NDRG1 knockdown disrupted tight junctions of airway epithelial cells. Next, we analyzed the effects of NDRG1 knockdown on the expression of tight and adhesion junction molecules. NDRG1 knockdown significantly decreased only claudin‐9 expression, but did not decrease other claudin family molecules, such as E‐cadherin, and ZO‐1, ‐2, or ‐3. Knockdown of claudin‐9 markedly impaired the barrier function in airway epithelial cells. These results suggest that NDRG1 is important for the barrier integrity in airway epithelial cells.
Proton‐Reduction Reaction Catalyzed by Homoleptic Nickel–bis‐1,2‐dithiolate Complexes: Experimental and Theoretical Mechanistic Investigations
Authors: Zarkadoulas Athanasios , Field Martin J. , Artero Vincent , Mitsopoulou Christiana A. 
Published: February 2017

AbstractA series of homoleptic monoanionic nickel dithiolene complexes [Ni(bdt)2](NBu4), [Ni(tdt)2](NBu4), and [Ni(mnt)2](NBu4) containing the ligands benzene‐1,2‐dithiolate (bdt2−), toluene‐3,4‐dithiolate (tdt2−), and maleonitriledithiolate (mnt2−), respectively, were employed as electrocatalysts in the hydrogen‐evolution reaction with trifluoroacetic acid as the proton source in acetonitrile. All complexes are active catalysts with TONs reaching 113, 158, and 6 for [Ni(bdt)2](NBu4), [Ni(tdt)2](NBu4), and [Ni(mnt)2](NBu4), respectively. The Faradaic yield for the hydrogen evolution reaction reaches 88 % for 2−, which also displays the minimal overpotential requirement value (467 mV) within the series. Two pathways for H2 evolution can be hypothesized that differ in the sequence of protonation and reduction steps. DFT calculations are in agreement with experimental data and indicate that protonation at sulfur follows the reduction to the dianion. Hydrogen evolves from the direduced–diprotonated form via a highly distorted nickel hydride intermediate. The effects of acid strength and concentration in the hydrogen‐evolving mechanism are also discussed.
A Tethered Ru–S Complex with an Axial Chiral Thiolate Ligand for Cooperative Si–H Bond Activation: Application to Enantioselective Imine Reduction
Authors: Wübbolt Simon , Maji Modhu Sudan , Irran Elisabeth , Oestreich Martin 
Published: February 2017

AbstractAn axial chiral version of the 2,6‐dimesitylphenyl group attached to sulfur is reported. Its multistep preparation starts from (S)‐binol, and the thiol group is established by a racemization‐free thermal Newman–Kwart rearrangement. The new chiral thiolate ligand decorated with one mesityl group is used in the synthesis of a tethered ruthenium chloride complex. Its spectroscopic characterization revealed solvent‐dependent epimerization at the ruthenium center. The major diastereomer is crystallographically characterized. Chloride abstraction with tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate (NaBArF4) yields the corresponding coordinatively unsaturated ruthenium complex with the Ru−S bond exposed. Si−H bond activation at this Ru−S bond proceeds in syn fashion but with moderate facial selectivity (d.r.=70:30), generating diastereomeric chiral‐at‐ruthenium hydrosilane adducts. Their application to catalytic imine hydrosilylation led to promising enantioinduction (40 % ee), thereby providing proof of concept for asymmetric catalysis involving cooperative Si−H bond activation.
Small Molecule Mixture Analysis by Heteronuclear NMR under Spin Diffusion Conditions in Viscous DMSO–Water Solvent
Authors: Lameiras Pedro , Patis Solène , Jakhlal Jouda , Castex Stéphanie , Clivio Pascale , Nuzillard Jean‐Marc 
Published: February 2017

AbstractSpin diffusion in NMR occurs for small‐ and medium‐sized molecules when their tumbling rate reduces in solution so that magnetization exchange by longitudinal cross relaxation becomes highly efficient. Composite DMSO–water viscous solvents were used for the first time to access the individual NMR spectra of a mixture components in spin diffusion conditions. The easy handling and high dissolution power of [D6]DMSO/H2O offers a wide range of potential applications for polar and moderately apolar mixture analysis. In addition to 2D 1H‐1H NOESY and 1H‐13C HSQC‐NOESY, 1H‐15N HSQC‐NOESY, 1D and 2D 1H‐19F heteronuclear NOESY (HOESY) experiments were set up to offer new ways to individualize molecules within a mixture. This article reports the analysis of a polar mixture of four dipeptides dissolved in [D6]DMSO/H2O (7:3 v/v) and that of a medium‐polarity fluorinated dinucleotide dissolved in [D6]DMSO/H2O (8:2 v/v) by means of spin diffusion in NOESY, HOESY, and HSQC–NOESY experiments.
Anthropometric parameters and the incidence of atrial fibrillation in older people: the PRO.V.A study
Authors: Trevisan Caterina , Maggi Stefania , Curreri Chiara , Nante Giovanni , Noale Marianna , De Rui Marina , Perissinotto Egle , Sartori Leonardo , Zambon Sabina , Crepaldi Gaetano , Manzato Enzo , Sergi Giuseppe 
Published: February 2017

BackgroundAtrial fibrillation (AF) has been associated with body size and central obesity, but the impact of different anthropometric measures in this relationship has been inadequately investigated.HypothesisIn this study, we examined the association between baseline anthropometric parameters with the incidence of AF in older people, hypothesizing that body size could impact the onset of AF more than fat distribution.MethodsOur study included 1764 participants with a mean age of 74.3 ± 6.9 years and no AF at baseline. Body mass index (BMI), body height, body surface area (BSA), waist and hip circumference, waist‐to‐stature ratio, waist‐to‐hip ratio, and mid–upper arm circumference (MUAC) were measured by trained physicians. AF was assessed after a 4.4‐year follow‐up.ResultsThere were 115 new cases of AF observed after the follow‐up. Taking lower values of these measures for reference, the adjusted AF risk was 2.42 (95% confidence interval [CI]:1.88‐3.12) for the highest stature quartile, 1.36 (95% CI:1.15‐1.62) for BMI ≥30 kg/m2, 2.12 (95% CI:1.73–2.59) for the highest BSA quartile, 1.38 (95% CI: 1.21‐1.56) for higher MUAC, and 1.39 (95% CI: 1.23‐1.58, P < 0.0001) for higher hip circumference values. Central obesity did not seem to relevantly predict the onset of AF in our sample. Stature revealed the strongest impact on the onset of AF (5% higher risk of developing AF per 1 cm increase in height).ConclusionsBody size, particularly tall stature and obesity, but not fat distribution, seems to be associated with the risk of AF in the elderly.
A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma
Authors: Goyal Lipika , Zheng Hui , Yurgelun Matthew B. , Abrams Thomas A. , Allen Jill N. , Cleary James M. , Knowles Michelle , Regan Eileen , Reardon Amanda , Khachatryan Anna , Jain Rakesh K. , Nardi Valentina , Borger Darrell R. , Duda Dan G. , Zhu Andrew X. 
Published: February 2017

BACKGROUNDAdvanced cholangiocarcinoma carries a poor prognosis, and no standard treatment exists beyond first‐line gemcitabine/platinum‐based chemotherapy. A single‐arm, phase 2 and biomarker study of cabozantinib, a multikinase inhibitor with potent activity against vascular endothelial growth factor receptor 2 (VEGFR2) and MET, was performed for patients with advanced refractory cholangiocarcinoma.METHODSPreviously treated patients with unresectable or metastatic cholangiocarcinoma received cabozantinib (60 mg orally and daily on a continuous schedule). The primary endpoint was progression‐free survival (PFS). Tumor MET expression and plasma biomarkers were evaluated.RESULTSThe study enrolled 19 patients with cholangiocarcinoma (female, 68%; median age, 67 years; intrahepatic vs extrahepatic, 84% vs 16%). The median PFS was 1.8 months (95% confidence interval, 1.6‐5.4 months), and the median overall survival (OS) was 5.2 months (95% confidence interval, 2.7‐10.5 months). Grade 3/4 adverse events occurred in 89% of the patients and included neutropenia (5%), hyperbilirubinemia (5%), epistaxis (5%), bowel perforation (5%), enterocutaneous fistulas (5%), and hypertension (11%). One patient with 3 + MET expression in the tumor stayed on treatment for 278 days, but the MET expression did not correlate with the outcomes in the overall study population. Plasma vascular endothelial growth factor, placental growth factor, and stromal cell–derived factor 1α increased and soluble VEGFR2 and angiopoietin 2 decreased after treatment (all P values < .01). Plasma tissue inhibitor of matrix metalloproteinase 1 was inversely correlated with PFS, and soluble MET (sMET) and interleukin 6 were inversely correlated with OS.CONCLUSIONSIn unselected patients with cholangiocarcinoma, cabozantinib demonstrated limited activity and significant toxicity. In the first clinical trial to assess the role of MET inhibition in cholangiocarcinoma, 1 patient with a MET‐high tumor had a prolonged benefit from treatment. Baseline plasma soluble MET was associated with OS. Any further development of this drug in cholangiocarcinoma should include a dose reduction and a biomarker‐driven approach. Cancer 2017;123:1979–1988. © 2017 American Cancer Society.
Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies
Authors: Miller Jacob A. , Kotecha Rupesh , Ahluwalia Manmeet S. , Mohammadi Alireza M. , Chao Samuel T. , Barnett Gene H. , Murphy Erin S. , Vogelbaum Michael A. , Angelov Lilyana , Peereboom David M. , Suh John H. 
Published: February 2017

BACKGROUNDThe current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies.METHODSPatients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes.RESULTSWithin the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)‐amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2‐positive (15.4 months), and luminal B (18.8 months) cohorts (P<.001). Among patients with HER2‐amplified disease, the median survival was extended with the use of both HER2 antibodies (17.9 months vs 15.1 months; P = .04) and TKIs (21.1 months vs 15.4 months; P = .03). The 12‐month cumulative incidences of local failure among molecular subtypes were 6.0% in the luminal A cohort, 10.3% in the luminal B cohort, 15.4% in the HER2‐positive cohort, and 9.9% in the basal cohort (P = .01). Concurrent HER2/epidermal growth factor receptor TKIs with stereotactic radiosurgery significantly decreased the 12‐month cumulative incidence of local failure from 15.1% to 5.7% (P<.001).CONCLUSIONSMolecular subtypes appear to be prognostic for survival and predictive of the response to radiotherapy. TKIs were found to improve survival and local control, and may decrease the rate of distant failure. To preserve neurocognition, these results support a paradigm of upfront radiosurgery and HER2‐directed therapy in the HER2‐amplified population, reserving whole‐brain radiotherapy for salvage. Cancer 2017;123:2283–2293. © 2017 American Cancer Society.
Enzyme Immobilized on Nanoporous Carbon Derived from Metal–Organic Framework: A New Support for Biodiesel Synthesis
Authors: Liu Li‐Hao , Shih Yung‐Han , Liu Wan‐Ling , Lin Chia‐Her , Huang Hsi‐Ya 
Published: February 2017

AbstractIn this study, nanoporous carbon (NPC) derived from metal–organic framework was used as support for the immobilization of Burkholderia cepacia lipase. The decorated aluminum oxide within the mesoporous NPC improved the enzyme loading efficiency as well as the catalytic ability for the transesterification of soybean oil, thus making it a promising green and sustainable catalytic system for industrial application.
NS1209/SPD 502, A Novel Selective AMPA Antagonist for Stroke, Neuropathic Pain or Epilepsy? Drug Development Lessons Learned
Authors: Keppel Hesselink Jan M. 
Published: February 2017

ABSTRACT

Preclinical Research

The selective AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid) receptor antagonist, NS1209 (also known as SPD 502) has been explored in several research and development campaigns since its selection as a lead drug candidate in the early 1990s by the Danish biotechnology company, NeuroSearch. The compound was successively tested in animal models of stroke, neuropathic pain and epilepsy. The preclinical data to support development for the treatment of stroke were incomplete, as the compound was administered after the stroke episode, and did not protect subcortical areas of the brain. Preclinical data for neuropathic pain and epilepsy appeared more promising, but the design of the Phase IIa studies in both indications was suboptimal, and an exploratory study in neuropathic pain, like one in refractory epilepsy gave inconclusive results. Preclinical data in pain models were much less convincing than reported by the authors in abstract and discussion sections. Due to a long preclinical sequential testing phase and insufficiently powered clinical trials, NS 1209 disappeared from the CNS development pipeline, while its patent protection exclusivity was markedly reduced due to the unfortunate slow speed in development—a phenomenon far from unusual in CNS drug discovery. NeuroSearch ceased operations as an R&D entity in 2012 and its R & D portfolio was transferred to Teva Pharmaceuticals and to a spin off, Saniona A/S. Based on an in‐depth case analysis of the development of NS 1209, a number of recommendations are given to reduce chances of failure during clinical development of neuropathic pain compounds and, more generally, of CNS compounds. Drug Dev Res 78 : 75‐80, 2017. © 2017 Wiley Periodicals, Inc.
Methane seepage in a Cretaceous greenhouse world recorded by an unusual carbonate deposit from the Tarfaya Basin, Morocco
Authors: Smrzka Daniel , Zwicker Jennifer , Kolonic Sadat , Birgel Daniel , Little Crispin T.S. , Marzouk Akmal M. , Chellai El Hassane , Wagner Thomas , Peckmann Jörn 
Published: February 2017

AbstractDuring the Cretaceous major episodes of oceanic anoxic conditions triggered large scale deposition of marine black shales rich in organic carbon. Several oceanic anoxic events (OAEs) have been documented including the Cenomanian to Turonian OAE 2, which is among the best studied examples to date. This study reports on a large limestone body that occurs within a black shale succession exposed in a coastal section of the Tarfaya Basin, Morocco. The black shales were deposited in the aftermath of OAE 2 in a shallow continental sea. To decipher the mode and causes of carbonate formation in black shales, a combination of element geochemistry, palaeontology, thin section petrography, carbon and oxygen stable isotope geochemistry and lipid biomarkers are used. The 13C‐depleted biphytanic diacids reveal that the carbonate deposit resulted, at least in part, from microbially mediated anaerobic oxidation of methane in the shallow subseafloor at a hydrocarbon seep. The lowest obtained δ13Ccarbonate values of −23·5‰ are not low enough to exclude other carbon sources than methane apart from admixed marine carbonate, indicating a potential contribution from in situ remineralization of organic matter contained in the black shales. Nannofossil and trace metal inventories of the black shales and the macrofaunal assemblage of the carbonate body reveal that environmental conditions became less reducing during the deposition of the background shales that enclose the carbonate body, but the palaeoenvironment was overall mostly characterized by high productivity and episodically euxinic bottom waters. This study reconstructs the evolution of a hydrocarbon seep that was situated within a shallow continental sea in the aftermath of OAE 2, and sheds light on how these environmental factors influenced carbonate formation and the ecology at the seep site.
Environmental enrichment, sexual dimorphism, and brain size in sticklebacks
Authors: Toli Elisavet A. , Noreikiene Kristina , DeFaveri Jacquelin , Merilä Juha 
Published: February 2017

AbstractEvidence for phenotypic plasticity in brain size and the size of different brain parts is widespread, but experimental investigations into this effect remain scarce and are usually conducted using individuals from a single population. As the costs and benefits of plasticity may differ among populations, the extent of brain plasticity may also differ from one population to another. In a common garden experiment conducted with three‐spined sticklebacks (Gasterosteus aculeatus) originating from four different populations, we investigated whether environmental enrichment (aquaria provided with structural complexity) caused an increase in the brain size or size of different brain parts compared to controls (bare aquaria). We found no evidence for a positive effect of environmental enrichment on brain size or size of different brain parts in either of the sexes in any of the populations. However, in all populations, males had larger brains than females, and the degree of sexual size dimorphism (SSD) in relative brain size ranged from 5.1 to 11.6% across the populations. Evidence was also found for genetically based differences in relative brain size among populations, as well as for plasticity in the size of different brain parts, as evidenced by consistent size differences among replicate blocks that differed in their temperature.
Sensitivity of sea urchin fertilization to pH varies across a natural pH mosaic
Authors: Kapsenberg Lydia , Okamoto Daniel K. , Dutton Jessica M. , Hofmann Gretchen E. 
Published: February 2017

AbstractIn the coastal ocean, temporal fluctuations in pH vary dramatically across biogeographic ranges. How such spatial differences in pH variability regimes might shape ocean acidification resistance in marine species remains unknown. We assessed the pH sensitivity of the sea urchin Strongylocentrotus purpuratus in the context of ocean pH variability. Using unique male–female pairs, originating from three sites with similar mean pH but different variability and frequency of low pH (pHT ≤ 7.8) exposures, fertilization was tested across a range of pH (pHT 7.61–8.03) and sperm concentrations. High fertilization success was maintained at low pH via a slight right shift in the fertilization function across sperm concentration. This pH effect differed by site. Urchins from the site with the narrowest pH variability regime exhibited the greatest pH sensitivity. At this site, mechanistic fertilization dynamics models support a decrease in sperm–egg interaction rate with decreasing pH. The site differences in pH sensitivity build upon recent evidence of local pH adaptation in S. purpuratus and highlight the need to incorporate environmental variability in the study of global change biology.