bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Diastereoselective Synthesis of Novel 5‐Substituted Morpholine‐3‐phosphonic Acids: Further Exploitation of N‐Acyliminium Intermediates.
Authors: Bonilla‐Landa Israel , Viveros‐Ceballos Jose Luis , Ordonez Mario
Published: September 2014

Diastereoselective nucleophilic addition of trimethyl phosphite to an N‐acyliminium intermediate derived from substrate (I) gives cyclic α‐aminophosphonates.
ChemInform Abstract: Natural Tetraponerines: A General Synthesis and Antiproliferative Activity.
Authors: Bosque Irene , Gonzalez‐Gomez Jose C. , Loza Maria Isabel , Brea Jose
Published: September 2014

A stereocontrolled general methodology to synthesize the eight natural tetraponerines (I) to (IV) is described and the anticancer activity of tetraponerines bearing a pentyl moiety against four different carcinoma human cell lines is examinated.
ChemInform Abstract: Identification of Thuridillin‐Related Aldehydes from Mediterranean Sacoglossan Mollusk Thuridilla hopei.
Authors: Carbone Marianna , Ciavatta M. Letizia , De Rinaldis Gianluca , Castelluccio Francesco , Mollo Ernesto , Gavagnin Margherita
Published: September 2014

Northuridillonal (I), dihydronorthuridillonal (IIa) and deacetyldehydronorthuridillonal (IIb) are isolated and their structures are evaluated.
ChemInform Abstract: Progress in Electrochemical Synthesis of Magnetic Iron Oxide Nanoparticles
Authors: Ramimoghadam Donya , Bagheri Samira , Hamid Sharifah Bee Abd
Published: September 2014

Review: 258 refs.
ChemInform Abstract: L10 FePt‐Based Thin Films for Future Perpendicular Magnetic Recording Media
Authors: Varvaro G. , Laureti S. , Fiorani D.
Published: September 2014

Review: 79 refs.
ChemInform Abstract: Simple Trivalent Organoaluminum Species: Perspectives on Structure, Bonding, and Reactivity
Authors: Lewinski Janusz , Wheatley Andrew E. H.
Published: September 2014

Review: 290 refs.
ChemInform Abstract: Biologically Driven Synthesis of Pyrazolo[3,4‐d]pyrimidines as Protein Kinase Inhibitors: An Old Scaffold as a New Tool for Medicinal Chemistry and Chemical Biology Studies
Authors: Schenone Silvia , Radi Marco , Musumeci Francesca , Brullo Chiara , Botta Maurizio
Published: September 2014

Review: 251 refs.
ChemInform Abstract: An Overview of N‐Heterocyclic Carbenes
Authors: Hopkinson Matthew N. , Richter Christian , Schedler Michael , Glorius Frank
Published: September 2014

Review: general properties and use; 100 refs.
ChemInform Abstract: The Hydrolysis of Carbonyl Sulfide at Low Temperature: A Review
Authors: Zhao Shunzheng , Yi Honghong , Tang Xiaolong , Jiang Shanxue , Gao Fengyu , Zhang Bowen , Zuo Yanran , Wang Zhixiang
Published: September 2014

Review: 80 refs.
ChemInform Abstract: Microwave‐Assisted Synthesis of Six‐Membered S‐Heterocycles
Authors: Kaur Navjeet , Kishore Dharma
Published: September 2014

Review: [85 refs.
ChemInform Abstract: Mixture‐Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α‐Antitrypsin Deficiency
Authors: Chang Yi‐Pin , Chu Yen‐Ho
Published: September 2014

Review: 63 refs.
ChemInform Abstract: Porphyrins and Phthalocyanines Decorated with Dendrimers: Synthesis and Biomedical Applications
Authors: Figueira Flavio , Pereira Patricia M. R. , Silva Sandrina , Cavaleiro Jose A. S. , Tome Joao P. C.
Published: September 2014

Review: 100 refs.
ChemInform Abstract: Microwave‐Assisted Synthesis of Benzo‐Fused Seven‐Membered Azaheterocycles
Authors: Sakhuja Rajeev , Bajaj Kiran , Abdul Shakoor S. M. , Kumar Anil
Published: September 2014

Review: such as benzodiazepines, benzothiazepines and benzoxazepines; 102 refs.
ChemInform Abstract: Synthesis of 2,3,3,3‐Tetrafluoropropene (HFO‐1234yf) on Chrome‐Magnesium Fluoride Catalyst
Authors: Jukov A. A. , Barabanov V. G. , Ismagilov N. U. , Trukshin Y. G. , Shelopin G. G.
Published: September 2014

Review: 8 refs.
ChemInform Abstract: Nanomagnetism. Principles, Nanostructures, and Biomedical Applications
Authors: Yang Ce , Hou Yang‐Long , Gao Song
Published: September 2014

Review: 63 refs.
ChemInform Abstract: High Spin Molecules Directed Towards Molecular Magnets
Authors: Baumgarten Martin
Published: September 2014

Review: 194 refs.
ChemInform Abstract: Recent Advances in Silver‐Based Heterogeneous Catalysts for Green Chemistry Processes
Authors: Wen Chao , Yin Anyuan , Dai Wei‐Lin
Published: September 2014

Review: 100 refs.
ChemInform Abstract: Methylated Azoles, 2‐Tetrazenes, and Hydrazines
Authors: Miro Sabate Carles , Delalu Henri
Published: September 2014

Review: 42 refs.
ChemInform Abstract: Chemical‐Looping Combustion of Solid Fuels ‐ Status of Development
Authors: Lyngfelt Anders
Published: September 2014

Review: 68 refs.
Predictors and Outcome of Sustained Improvement in Left Ventricular Function in Dilated Cardiomyopathy
Authors: Blechman Ido , Arad Michael , Nussbaum Tamar , Goldenberg Ilan , Freimark Dov
Published: September 2014

Background

Improvement in the left ventricular ejection fraction (LVEF) may occur in patients with dilated cardiomyopathy (DCM).

Hypothesis

There are different implications of persistent versus transient improvement in LVEF among DCM patients receiving contemporary therapy.

Methods

We studied 188 patients with nonischemic DCM. Persistent improvement in LVEF (PIEF) was defined as LVEF increase by at least 10% compared to baseline, and found in 2 separate echo‐Doppler exams performed at least 12 months apart. Increased LVEF in echo 2, which was not sustained in echo 3, was defined as transient improvement in LVEF (TIEF).

Results

Over an average follow‐up of 6.8 years, PIEF occurred in 61 (33%) patients, predicting a better long‐term outcome (P < 0.001) in a combined end‐point comprising death, heart transplantation, or the need for a ventricular assist device. The TIEF group had an intermediate course and were closer to nonimprovers (P = 0.003 vs PIEF). Multivariate logistic regression identified the following independent predictors of PIEF: shorter disease duration, pregnancy‐associated disease, left ventricular hypertrophy, and baseline LVEF ≤25%. A score to predict PIEF assigned 1 point to each of the following: disease duration <3 years and no familial cardiomyopathy; pregnancy‐associated presentation; basal LVEF ≤25%; and left ventricular wall thickness ≥12. A score of ≥3 was present in 44% of the patients, reliably predicting PIEF in 91% (P = 0.01).

Conclusions

Persistent improvement in LVEF is associated with improved long‐term prognosis. Baseline clinical parameters can be used to identify patients likely to demonstrate PIEF, thereby allowing tailored management in this population.
Evaluation of Ascending Aorta Wall in Rheumatoid Arthritis by Tissue and Strain Doppler Imaging During Anti–Tumor Necrosis Factor‐α Therapy
Authors: Vizzardi Enrico , Cavazzana Ilaria , Sciatti Edoardo , Bonadei Ivano , D'Aloia Antonio , Tincani Angela , Franceschini Franco , Metra Marco
Published: September 2014

Background

Patients with rheumatoid arthritis (RA) are at increased risk of vascular events. Data on the effects of tumor necrosis factor‐α (TNF‐α) blocking agents on aortic vascular function are still debated.

Hypothesis

To evaluate the effects of anti–TNF‐α treatment on elastic properties of the ascending aorta (distensibility, stiffness, and tissue Doppler imaging [TDI] strain) in RA patients.

Methods

We prospectively followed 13 patients affected by RA without cardiovascular risk factors for 1 year during anti–TNF‐α treatment. Every subject received an echocardiographic examination before starting anti–TNF‐α drugs and after 1 year. Aortic elastic properties were calculated from the echocardiographically derived thoracic aortic diameters, and TDI strain was measured on the wall of the ascending aorta 3 cm above the aortic valve.

Results

We found lower distensibility (12.9 ± 3.5 vs 21.5 ± 7.5 mm Hg−1; P <0.001) and a higher stiffness index (21.3 ± 3.6 vs 11.7 ± 1.4; P <0.001) in RA cases at baseline compared with values after 1 year of treatment. Peak systolic (S′) and diastolic (E′ and A′) waves of the aortic wall TDI were similar at baseline and at 1 year follow‐up (S′ wave: 5.6 ± 2.2 cm/s vs 6.5 ± 2.6 cm/s, E′ wave: −4.6 ± 2.9 vs −5.0 ± 1.2 cm/s, A′ wave: −5.6 ± 0.19 vs −5.9 ± 2.05 cm/s), whereas TDI strain of the aortic wall was improved after anti–TNF‐α treatment (−23.7 ± 1.4% vs −31.6 ± 2.8%, P < 0.001).

Conclusions

Anti–TNF‐α treatment after 12 months significantly modifies the elastic properties of the aorta. This may reflect the favorable changes in its elastic tissue after anti–TNF‐α treatment in RA patients without cardiovascular risk factors. This suggests a potential cardiovascular risk benefit.
Effective population size does not predict codon usage bias in mammals
Authors: Kessler Michael D. , Dean Matthew D.
Published: September 2014

Synonymous codons are not used at equal frequency throughout the genome, a phenomenon termed codon usage bias (CUB). It is often assumed that interspecific variation in the intensity of CUB is related to species differences in effective population sizes (Ne), with selection on CUB operating less efficiently in species with small Ne. Here, we specifically ask whether variation in Ne predicts differences in CUB in mammals and report two main findings. First, across 41 mammalian genomes, CUB was not correlated with two indirect proxies of Ne (body mass and generation time), even though there was statistically significant evidence of selection shaping CUB across all species. Interestingly, autosomal genes showed higher codon usage bias compared to X‐linked genes, and high‐recombination genes showed higher codon usage bias compared to low recombination genes, suggesting intraspecific variation in Ne predicts variation in CUB. Second, across six mammalian species with genetic estimates of Ne (human, chimpanzee, rabbit, and three mouse species: Mus musculus, M. domesticus, and M. castaneus), Ne and CUB were weakly and inconsistently correlated. At least in mammals, interspecific divergence in Ne does not strongly predict variation in CUB. One hypothesis is that each species responds to a unique distribution of selection coefficients, confounding any straightforward link between Ne and CUB.
Cloud water interception and element deposition differ largely between Norway spruce stands along an elevation transect in Harz Mountains, Germany
Authors: Köhler Lars , Leuschner Christoph , Hauck Markus , Hertel Dietrich
Published: September 2014

Cloud deposition can contribute a significant amount of water and elements to montane forests and thus play an important role in the hydrological and biochemical cycles of these ecosystems. However, elevational pattern in cloud and throughfall input to forest ecosystems and the associated chemical element fluxes are poorly understood so far. We studied gross precipitation, throughfall and cloud water deposition, and the associated fluxes of elements (N, P, Ca, K, Mg and Na) in five mature stands of Norway spruce along an elevation transect from lowlands to the alpine treeline (420–1060 m) at Mt Brocken (Harz Mountains, Germany). We tested the hypotheses that water input increases with elevation despite a reduction in intercepting plant surfaces, leading to higher inputs of nitrogen and other elements to high‐elevation forests than in lower‐elevation stands. Gross precipitation (only snow‐free period) rose by 75% towards the treeline, but water input with throughfall increased by 350% because of a large increase in cloud water deposition (from 2 mm at 420 m to 160–200 mm at 1000 m in the study period). Element fluxes with gross precipitation were not uniformly related to elevation across all six elements. However, element fluxes via throughfall showed a positive correlation with elevation for all elements. Thus, the upper montane spruce forests received ~50–150% higher atmospheric inputs of base cations and inorganic N and ~200% higher P inputs than lower‐elevation forests. We conclude that elevation does have a large influence on the atmospheric water and element inputs in temperate mountain forests. Copyright © 2014 John Wiley & Sons, Ltd.
Human regulatory T cells lack the cyclophosphamide‐extruding transporter ABCB1 and are more susceptible to cyclophosphamide‐induced apoptosis
Authors: Dimeloe Sarah , Frick Corina , Fischer Marco , Gubser Patrick M. , Razik Leyla , Bantug Glenn R. , Ravon Morgane , Langenkamp Anja , Hess Christoph
Published: September 2014

ATP‐binding cassette (ABC) transporters, including ABC‐transporter B1 (ABCB1), extrude drugs, metabolites, and other compounds (such as mitotracker green (MTG)) from cells. Susceptibility of CD4+ regulatory T (Treg) cells to the ABCB1‐substrate cyclophosphamide (CPA) has been reported. Here, we characterized ABCB1 expression and function in human CD4+ T‐cell subsets. Naïve, central memory, and effector‐memory CD4+ T cells, but not Treg cells, effluxed MTG in an ABCB1‐dependent manner. In line with this, ABCB1 mRNA and protein was expressed by nonregulatory CD4+ T‐cell subsets, but not Treg cells. In vitro, the ABCB1‐substrate CPA was cytotoxic for Treg cells at a 100‐fold lower dose than for nonregulatory counterparts, and, inversely, verapamil, an inhibitor of ABC transporters, increased CPA‐toxicity in nonregulatory CD4+ T cells but not Treg cells. Thus, Treg cells lack expression of ABCB1, rendering them selectively susceptible to CPA. Our findings provide mechanistic support for therapeutic strategies using CPA to boost anti‐tumor immunity by selectively depleting Treg cells.
Chemodosimetric Detection of the Acetate Anion by Using the Template Reaction Method via a Fluorescence “Turn‐Off” Signal
Authors: Das Sudhanshu , Jana Sankar , Chakraborty Prateeti , Sanyal Ria , Maiti Dilip Kumar , Guchhait Nikhil , Zangrando Ennio , Das Debasis
Published: September 2014

The compartmental ligand 2,6‐bis[2‐(N‐ethyl)thiopheneiminomethyl]‐4‐chlorophenol (HL) undergoes Cu(ClO4)2 induced partial hydrolysis to yield a monoamine ligand 4‐chloro‐2‐formyl‐6‐[2‐(thiophen‐2‐yl)ethyliminomethyl]phenol (HL′). On further reaction with Cu(ClO4)2, HL′ produces a dinuclear complex, [Cu2(L′)2(ClO4)2] (2), which has been characterized in solution by UV/Vis, ATR, NMR, and ESI‐MS spectral techniques and in the solid state by X‐ray single‐crystal structure analysis. The in situ generated 2 is highly fluorescent. On reaction with sodium acetate it transforms to a fluorescence inactive tetranuclear species, [Cu4(L)2(OAc)4(O)] (3), and thereby acts as an excellent chemodosimeter for selective detection of the acetate anion via fluorescence “turn‐off” signalling. The direct reaction of HL and copper(II) acetate dihydrate yielded another fluorescence inactive tetranuclear species, [Cu4(L)2(OAc)4(O)] (1), which is a diastereoisomer of 3 as is evident from X‐ray single‐crystal structural analyses.
Syntheses and Properties of Multiferrocenylated Corannulenes
Authors: Topolinski Berit , Schmidt Bernd M. , Schwagerus Sergej , Kathan Michael , Lentz Dieter
Published: September 2014

The syntheses and properties of corannulenes bearing different numbers and types of ferrocenyl groups are described. Six different monoferrocenylated corannulenes were synthesized, and the crystal structure of 1‐corannulenyl‐1′‐(ferrocenyl)benzene was elucidated by single‐crystal X‐ray analysis. Further, diferrocenylated corannulenes bearing methyl or trifluoromethyl groups are reported. Buckybowls with four and five ferrocenyl substituents were synthesized from tetrabromocorannulene and the symmetrical pentachlorocorannulene. The molecular structure and nutshell‐like crystal packing of a tetraferrocenylated corannulene was determined by single‐crystal X‐ray analysis. Additionally, all compounds presented herein were subjected to electrochemical and optical measurements in solution.
Prussian Blue Films Produced by Pentacyanidoferrate(II) and Their Application as Active Electrochemical Layers
Authors: Morandi Pires Bruno , Venturinelli Jannuzzi Sergio Augusto , Barboza Formiga André Luiz , Alves Bonacin Juliano
Published: September 2014

Iron complexes such as ferri/ferrocyanides are usually employed as electrochemical mediators in portable devices for the quick diagnosis of diseases. Stable complexes designed for the electrochemical active layer may render devices with better performance and lifetimes than conventional devices. In this work we have synthesized and characterized spectroscopically, electrochemically, and by DFT the complex Na4[Fe(CN)5(isn)] (isn = isonicotinate). This complex was used as a single‐source precursor of Prussian Blue (PB) in solution at pH 2.0 and 3.0, as confirmed by UV/Vis spectroscopy. Potentiostatic deposition of PB onto glassy carbon electrodes provided stable films at pH 3.0 and 5.0, with electrocatalytic activity for ascorbic acid oxidation with a linear response in the range 20–200 μM and an limit of detection of 12 μM. The anodic peak potential of the modified electrodes varied with solution pH with a minimum value of 0.350 V versus NHE at pH 5.0.
Molecular cloning and tissue mRNA levels of 15 genes involved in lipid metabolism in Synechogobius hasta
Authors: Chen Qi‐Liang , Luo Zhi , Huang Chao , Zheng Jia‐Lang , Pan Ya‐Xiong , Song Yu‐Feng , Hu Wei
Published: September 2014

The regulation of lipid metabolism is complex, and is currently an extensive area of research. In this study, the partial sequences of 15 genes involved in lipid metabolism were cloned from the liver of Synechogobius hasta, including g6pd, 6pgd, me, icdh, fas, accα, accβ, lpl, atgl, hsla, hslb, cpt 1a, srebp‐1, pparα, and pparγ. Phylogenetic analysis further identified these genes, and confirmed the classification and evolutionary status of S. hasta. mRNA of all genes was detected in the liver, spleen, muscle, gill, brain, intestine, and heart, but at varying levels.

Practical applications: Excessive fat accumulation and disordered lipid metabolism have become serious problems in the sustainable and healthy development of aquaculture. The present study facilitates studies on the regulation of lipid metabolism at the molecular level in fish. The tissue expression profiles of genes increase our understanding of their physiological roles.

In this study, the partial sequences of 15 genes involved in lipid metabolism were cloned and characterized from Synechogobius hasta, including g6pd, 6pgd, me, icdh, fas, accα, accβ, lpl, atgl, hsla, hslb, cpt 1a, srebp‐1, pparα, and pparγ. Phylogenetic analysis further identified these genes, and confirmed the classification and evolutionary status of S. hasta. mRNA of all genes was detected in the liver, spleen, muscle, gill, brain, intestine, and heart, but at the varying levels.
The Boulton–Katritzky Reaction: A Kinetic Study of the Effect of 5‐Nitrogen Substituents on the Rearrangement of Some (Z)‐Phenylhydrazones of 3‐Benzoyl‐1,2,4‐oxadiazoles
Authors: Frenna Vincenzo , Palumbo Piccionello Antonio , Cosimelli Barbara , Ghelfi Franco , Spinelli Domenico
Published: September 2014

The kinetics of the ring‐into‐ring conversion of some new (Z)‐phenylhydrazones of 3‐benzoyl‐1,2,4‐oxadiazole containing different nitrogen‐substituents at C‐5 (3b–d; X = NHMe, NMe2, and NHCOMe) into the relevant triazoles 4b–d have been examined in a wide range of pS+ (0.1–11.9) in 1:1 (v/v) dioxane/water solution. The obtained results have been compared with previous data concerning the (Z)‐phenylhydrazone of 5‐amino‐3‐benzoyl‐1,2,4‐oxadiazole (3a; X = NH2). All of the studied (Z)‐phenylhydrazones rearrange through three different pathways (specific acid‐catalysed, uncatalysed and general base‐catalysed). The different effects of the substituents on the course of the rearrangement in the three pathways have been examined.
Cesium Carbonate Promoted Direct Arylation of Hydroxylamines and Oximes with Diaryliodonium Salts
Authors: Yang Yang , Wu Xunshen , Han Jianwei , Mao Song , Qian Xiaofei , Wang Limin
Published: September 2014

A transition‐metal‐free approach for the arylation of hydroxylamines and oximes with diaryliodonium salts was developed. The reaction proceeded smoothly at room temperature in the presence of cesium carbonate. As a result, a wide range of N‐ and O‐arylated hydroxylamines were synthesized in good to excellent yields (45–98 %).
One‐Pot Multiple Lithiation Processes of Fused Heterocycles
Authors: Jasselin‐Hinschberger Adeline , Comoy Corinne , Fort Yves
Published: September 2014

An efficient one‐pot process that involves two or three successive regioselective lithiation/electrophilic trapping stages has been developed that affords several polysubstituted derivatives in good overall yields by starting from 2‐chlorofuro[3,2‐b]pyridine.
Renewable energy choice: Cost and energy analysis of grid connected photovoltaic system in Malaysia
Authors: Heng Lim Choong , Al‐Amin Abul Quasem , Saidur R. , Ward T.A.
Published: September 2014

Conventional energy production methods rely upon combustion of hydrocarbon fuels, which exhaust gases that can elevate the temperature of the Earth's atmosphere (greenhouse effect). Alternative methods of power generation are being examined that do not have this negative environmental impact. This study investigates the potential use of a residential grid‐connected photovoltaic system in the Klang Valley of Malaysia. A 1–4 kW system would be capable of producing a RM 4,542.00 net profit per year, generating a total cash benefit of RM 95,382.00 in its 21 year project lifespan. Moreover, the system would significantly reduce greenhouse gas emissions (40,604 kg of carbon dioxide, 258 kg of sulfur dioxide, 120 kg of nitrous oxide, and 23 kg of carbon monoxide) throughout its 21 year project lifespan. The results of this study can be used to formulate effective renewable‐energy alternatives in Malaysia and elsewhere. © 2014 American Institute of Chemical Engineers Environ Prog, 34: 866–880, 2015
A review of terrestrial radar interferometry for measuring surface change in the geosciences
Authors: Caduff Rafael , Schlunegger Fritz , Kos Andrew , Wiesmann Andreas
Published: September 2014

This paper presents a review of the current state of the art in the use of terrestrial radar interferometry for the detection of surface changes related to mass movement. Different hardware‐types and acquisition concepts are described, which use either real or synthetic aperture for radar image formation. We present approaches for data processing procedures, paying special attention to the separation of high resolution displacement information from atmospheric phase variations. Recent case studies are used to illustrate applications in terrestrial radar interferometry for change detection. Applications range from detection and quantification of very slow moving (millimeters to centimeters per year) displacements in rock walls from repeat monitoring, to rapid processes resulting in fast displacements (~50 m/yr) acquired during single measurement campaigns with durations of only a few hours. Fast and episodic acting processes such as rockfall and snow avalanches can be assessed qualitatively in the spatial domain by mapping decorrelation caused by those processes. A concluding guide to best practice outlines the necessary preconditions that have to be fulfilled for successful application of the technique, as well as in areas characterized by rapid decorrelation. Empirical data from a Ku‐band sensor show the range of temporal decorrelation of different surfaces after more than two years for rock‐surfaces and after a few seconds to minutes in vegetated areas during windy conditions. The examples show that the displacement field can be measured for landslides in dense grassland, ice surfaces on flowing glaciers and snowpack creep. Copyright © 2014 John Wiley & Sons, Ltd.
Dysbiosis‐induced intestinal inflammation activates tumor necrosis factor receptor I and mediates alcoholic liver disease in mice
Authors: Chen Peng , Stärkel Peter , Turner Jerrold R. , Ho Samuel B. , Schnabl Bernd
Published: September 2014

Intestinal barrier dysfunction is an important contributor to alcoholic liver disease (ALD). Translocated microbial products trigger an inflammatory response in the liver and contribute to steatohepatitis. Our aim was to investigate mechanisms of barrier disruption after chronic alcohol feeding. A Lieber‐DeCarli model was used to induce intestinal dysbiosis, increased intestinal permeability, and liver disease in mice. Alcohol feeding for 8 weeks induced intestinal inflammation in the jejunum, which is characterized by an increased number of tumor necrosis factor alpha (TNF‐α)‐producing monocytes and macrophages. These findings were confirmed in duodenal biopsies from patients with chronic alcohol abuse. Intestinal decontamination with nonabsorbable antibiotics restored eubiosis, decreased intestinal inflammation and permeability, and reduced ALD in mice. TNF‐receptor I (TNFRI) mutant mice were protected from intestinal barrier dysfunction and ALD. To investigate whether TNFRI on intestinal epithelial cells mediates intestinal barrier dysfunction and ALD, we used TNFRI mutant mice carrying a conditional gain‐of‐function allele for this receptor. Reactivation of TNFRI on intestinal epithelial cells resulted in increased intestinal permeability and liver disease that is similar to wild‐type mice after alcohol feeding, suggesting that enteric TNFRI promotes intestinal barrier dysfunction. Myosin light‐chain kinase (MLCK) is a downstream target of TNF‐α and was phosphorylated in intestinal epithelial cells after alcohol administration. Using MLCK‐deficient mice, we further demonstrate a partial contribution of MLCK to intestinal barrier dysfunction and liver disease after chronic alcohol feeding. Conclusion: Dysbiosis‐induced intestinal inflammation and TNFRI signaling in intestinal epithelial cells mediate a disruption of the intestinal barrier. Therefore, intestinal TNFRI is a crucial mediator of ALD. (Hepatology 2015;61:883–894)
Double‐negative feedback loop between MicroRNA‐422a and forkhead box (FOX)G1/Q1/E1 regulates hepatocellular carcinoma tumor growth and metastasis
Authors: Zhang Jin , Yang Yun , Yang Tian , Yuan Shengxian , Wang Ruoyu , Pan Zeya , Yang Yuan , Huang Gang , Gu Fangming , Jiang Beige , Lin Chuan , Zhou Weiping
Published: September 2014

Growing evidence indicates that the aberrant expression of microRNAs (miRNAs) contributes to tumor development; however, the function of miRNAs in human hepatocellular carcinoma (HCC) remains largely undefined. In this study, we report that microRNA‐422a (miR‐422a) is significantly down‐regulated in HCC tumor samples and cell lines compared with normal controls, and its expression level is negatively correlated with pathological grading, recurrence, and metastasis. The restoration of miR‐422a expression in HCC tumor cells significantly inhibited cell proliferation and migration in vitro. At the same time, the overexpression of miR‐422a in HCC tumor cells significantly inhibits tumor growth and liver metastasis in xenograft tumor models. A mechanistic study identified three genes, forkhead box G1 (FOXG1), FOXQ1, and FOXE1, as miR‐422a targets in the regulation of HCC development. We also investigated the function of the three targets themselves in HCC tumorigenesis using RNAi manipulation and demonstrated that the knockdown of these targets led to significant inhibition of tumor cell proliferation and migration both in vitro and in vivo. More interestingly, a potential miR‐422a promoter region was identified. Both the promoter activity and miR‐422a expression were negatively regulated by the three targets, indicating that a double‐negative feedback loop exists between miR‐422a and its targets. Moreover, we explored the therapeutic potential of miR‐422a in HCC treatment and found that the therapeutic delivery of miR‐422a significantly inhibited tumor development in a xenograft tumor model and a diethylnitrosamine‐induced primary HCC model. Conclusion: Our findings show the critical roles of miR‐422a and its targets—FOXG1, FOXQ1, and FOXE1—in the regulation of HCC development and provide new potential candidates for HCC therapy. (Hepatology 2015;61:561‐573)
Long‐term changes in the fish assemblage structure of a shallow eutrophic reservoir (Lake Hídvégi, Hungary), with special reference to the exotic Carassius gibelio
Authors: Paulovits Gábor , Ferincz Árpád , Staszny Ádám , Weiperth András , Tátrai István , Korponai János , Mátyás Kálmán , Kováts Nora
Published: September 2014

European reservoirs are considered to be well characterized from many aspects. However, the description of long‐term sequence of events in the fish fauna is restricted and mostly limited to deep, oligomictic reservoirs. Lake Hídvégi is a shallow hypertrophic reservoir (average depth = 1.14 m), which started to operate in 1985. The main function of this reservoir has been to retain nutrients carried by the River Zala in order to protect the water quality of Lake Balaton. The changes in the fish fauna of Lake Hídvégi was monitored in selected localities using standard method (electrofishing). Species composition and assemblage structure changed significantly during the study period, between 1986 and 2011. Following the inundation, the rapid expansion of gibel carp (Carassius gibelio BLOCH, 1782) occurred, but after a peak this tendency turned. Surprisingly, based on the among‐years variance of the relative abundances, most of the species were not affected seriously by the invasion. By the end of the studied period, the native generalist roach (Rutilus rutilus L. 1758) became the most abundant species, amounting to more than 50% of the stock. By analyzing functional guilds, we identified an increasing trend in omnivore abundance, in parallel with the disappearance of planktivores. Our results suggest that the fish assemblage structure can be considered as metastable, disturbance tolerant and is mostly composed of generalist cyprinid species still after 29 years of operation.
Early osteoblast responses to orthopedic implants: Synergy of surface roughness and chemistry of bioactive ceramic coating
Authors: Aniket  , Reid Robert , Hall Benika , Marriott Ian , El‐Ghannam Ahmed
Published: September 2014

Pro‐osteogenic stimulation of bone cells by bioactive ceramic‐coated orthopedic implants is influenced by both surface roughness and material chemistry; however, their concomitant impact on osteoblast behavior is not well understood. The aim of this study is to investigate the effects of nano‐scale roughness and chemistry of bioactive silica‐calcium phosphate nanocomposite (SCPC50) coated Ti‐6Al‐4V on modulating early bone cell responses. Cell attachment was higher on SCPC50‐coated substrates compared to the uncoated controls; however, cells on the uncoated substrate exhibited greater spreading and superior quality of F‐actin filaments than cells on the SCPC50‐coated substrates. The poor F‐actin filament organization on SCPC50‐coated substrates is thought to be due to the enhanced calcium uptake by the ceramic surface. Dissolution analyses showed that an increase in surface roughness was accompanied by increased calcium uptake, and increased phosphorous and silicon release, all of which appear to interfere with F‐actin assembly and osteoblast morphology. Moreover, cell attachment onto the SCPC50‐coated substrates correlated with the known adsorption of fibronectin, and was independent of surface roughness. High‐throughput genome sequencing showed enhanced expression of extracellular matrix and cell differentiation related genes. These results demonstrate a synergistic relationship between bioactive ceramic coating roughness and material chemistry resulting in a phenotype that leads to early osteoblast differentiation. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1961–1973, 2015.
UCP2‐Related Mitochondrial Pathway Participates in Oroxylin A‐Induced Apoptosis in Human Colon Cancer Cells
Authors: Qiao Chen , Wei Libin , Dai Qinsheng , Zhou Yuxin , Yin Qian , Li Zhiyu , Xiao Yuanming , Guo Qinglong , Lu Na
Published: September 2014

Oroxylin A is a flavonoid extracted from the root of Scutellaria baicalensis Georgi. Our previous research demonstrated that oroxylin A have various anti‐tumor effects including apoptosis, cell cycle arrest, drug‐resistant reversion, and others. This paper explores the mechanism how oroxylin A induce apoptosis by regulating uncoupling protein 2 (UCP2) in human colon cancer cells. We found that the inhibition of UCP2 by UCP2 siRNA significantly increased the sensitivity of cells to drugs, reactive oxygen species (ROS) generation and the opening of mitochondrial permeability transition pore (MPTP) of CaCo‐2 cells. We also found that UCP2 inhibition could lead to ROS‐mediated MPTP activation. Furthermore, we demonstrated that oroxylin A triggered MPTP‐dependent pro‐apoptotic protein release from mitochondria to matrix and then induced apoptotic cascade by inhibiting UCP2. Intriguingly, the inhibition of UCP2 by oroxylin A was able to block Bcl‐2 translocation to the mitochondria, keeping MPTP at open‐state. In conclusion, we have demonstrated that UCP2 plays a key role in mitochondrial apoptotic pathway; UCP2s inhibition by oroxylin A triggers the MPTP opening, and promotes the apoptosis in CaCo‐2 cells. J. Cell. Physiol. 230: 1054–1063, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
An Efficient Synthesis of Novel 2‐(5‐indolyl)‐1H‐benzimidazole Derivatives and Evaluation of Their Antimicrobial Activities
Authors: Soodamani Venugopal , Patel Divyesh , Nayakanti Devanna , Josyula Ramanatham
Published: September 2014

In this paper, we report the synthesis of novel 2‐(5‐indolyl)‐1H‐benzimidazole derivatives. The methodology involves the Sonogashira reaction of 4‐(1H‐benzimidazol‐2‐yl)‐2‐bromo‐N,N‐dimethylaniline (3) with variety of terminal alkynes to get corresponding novel 4‐(1H‐benzimidazol‐2‐yl)‐2‐alkynyl‐N,N‐dimethylaniline derivatives (4). These compounds on iodocyclization afforded novel iodoindolylbenzimidazole derivatives (5). The resulting compounds were functionalized further via palladium‐mediated carbon–carbon bond formation for generating novel structurally diversified heterocyclic compounds. All these newly synthesized compounds were evaluated for antimicrobial activity.
Synthesis of Heteroaryl Thiazolidinones and Azetidinones under Conventional and Ultrasonication Methods
Authors: Ramachandra Reddy Putta , Padmaja Adivireddy , Padmavathi Venkatapuram
Published: September 2014

A simple and an efficient protocol for the synthesis of differently substituted thiazolidinones was reported under conventional and also under ultrasonication in one‐step and in two‐step methodologies. Heteroaryl Schiff's bases were also exploited to develop heteroaryl azetidinones under both conventional and ultrasound irradiation.
Extratropical cyclone climatology across eastern Canada
Authors: Plante Mathieu , Son Seok‐Woo , Atallah Eyad , Gyakum John , Grise Kevin
Published: September 2014

Extratropical cyclone (ETC) tracks across eastern Canada are examined by applying a Lagrangian tracking algorithm to the lower‐tropospheric relative vorticity field of reanalysis data. Both the seasonal cycle and the interannual variability of ETCs are quantified in terms of overall cyclone frequency, intensity, and regions of development and decay. We find that ETCs travelling to eastern Canada tend to develop over the Rockies, the Great Lakes and the US East Coast. The ETCs are most intense over Newfoundland and the North Atlantic Ocean, confirming previous findings. While ETCs at cities along the Atlantic coastline (e.g. St. John's) are dominated by East Coast cyclones (which are intense in winter), those inland (e.g. Toronto) track primarily from the Great Lakes. ETCs that develop over the Gulf of Mexico affect eastern Canada infrequently, but those that do tend to be intense. The interannual variability of the wintertime ETCs is influenced by the El Niño‐Southern Oscillation (ENSO). Significant ENSO‐related variability is found over most regions of southern Canada, except on the east coast. Although ETCs at Toronto are significantly modulated by ENSO, no visible changes are found at St. John's. These ENSO‐related ETC changes are mostly due to the shifts in ETC development regions, with minor changes in the travelling direction of ETCs.
Determination of exogenous epigallocatechin gallate peracetate in mouse plasma using liquid chromatography with quadrupole time‐of‐flight mass spectrometry
Authors: Chu Kai On , Man Gene Chi Wai , Chan Kwok Ping , Chu Ching Yan , Chan Tak Hang , Pang Chi Pui , Wang Chi Chiu
Published: September 2014

A robust method for the quantitation of epigallocatechin gallate peracetate in plasma for pharmacokinetic studies is lacking. We have developed a validated method to quantify this compound using liquid chromatography with quadrupole time‐of‐flight mass spectrometry with isopropanol and tert‐butyl methyl ether (3:10) extraction and thin‐layer chromatography purification. The epigallocatechin gallate peracetate‐1‐13C8 isotope was used as an internal standard. The linear range (r2 > 0.9950) was from 0.05 to 100.00 μg/mL. The lower limit of quantification of the method was 0.05 μg/mL. Reproducibility, coefficient of variation, was between 0.7 and 12.6% (n = 6), accuracy between 83.7 and 104.6% (n = 5), and recovery ranged from 82.4 to 109.0% (n = 4). Ion suppression was approximately 40%. No mass spectral peaks were found to interfere between the standard and internal standard or the blank plasma extracts. Epigallocatechin gallate peracetate in plasma was stably stored at –80°C over three months even after three freeze–thaw cycles. Extracts were stable in the sampler at 4°C for over 48 h. Plasma levels were maintained at 1.36 μg/mL for 360 min after intraorbital intravenous injection at 50 mg/kg in mice. This method can be used to reliably measure epigallocatechin gallate peracetate in plasma for pharmacokinetic studies.
Impact of resident surgeons on procedure length based on common pediatric otolaryngology cases
Authors: Puram Sidharth V. , Kozin Elliott D. , Sethi Rosh , Alkire Blake , Lee Daniel J. , Gray Stacey T. , Shrime Mark G. , Cohen Michael
Published: September 2014

Objectives/Hypothesis

Surgical education remains an important mission of academic medical centers. Financial pressures may favor improved operating room (OR) efficiency at the expense of teaching in the OR. We aim to evaluate factors, such as resident participation, associated with duration of total OR, as well as procedural time of common pediatric otolaryngologic cases.

Study Design

Retrospective cohort study.

Methods

We reviewed resident and attending surgeon total OR and procedural times for isolated tonsillectomy, adenoidectomy, tonsillectomy with adenoidectomy (T&A), and bilateral myringotomy with tube insertion between 2009 and 2013. We included cases supervised or performed by one of four teaching surgeons in children with American Society of Anesthesiology classification < 3. Regression analyses were used to identify predictors of procedural time.

Results

We identified 3,922 procedures. Residents had significantly longer procedure times for all procedures compared to an attending surgeon (4.9–12.8 minutes, P < 0.001). Differences were proportional to case complexity. In T&A patients, older patient age and attending surgeon identity were also significant predictors of increased mean procedural time (P < 0.05).

Conclusions

Resident participation contributes to increased procedure time for common otolaryngology procedures. We found that differences in operative time between resident surgeons and attending surgeons are proportional to the complexity of the case, with additional factors, such as attending surgeon identity and older patient age, also influencing procedure times. Despite the increased procedural time, our investigation shows that resident education does not result in excessive operative times beyond what may be reasonably expected at a teaching institution.

Level of Evidence

4. Laryngoscope, 125:991–997, 2015
Neonatal Mortality, Young Calf Slaughter and Milk Production during the Early Neolithic of North Western Mediterranean
Authors: Gillis R. , Carrère I. , Saña Seguí M. , Radi G. , Vigne J‐D.
Published: September 2014

The North‐Western Mediterranean witnessed a rapid expansion of farmers and their livestock during the Early Neolithic period. Depending on the region, cattle played a more or less important role in these communities; however how these animals were exploited for their milk is not clear. Here we investigate calf mortality to determine indirectly whether cattle dairying was practised by Early Neolithic stock herders. Age‐at‐death (AtD) frequencies for calves from two sites: Trasano (Italy, Impressa culture: 7–6th millennium BC) and La Draga (Spain, Cardial culture: 6th millennium BC) were estimated from dental eruption and development stages, and measurements of un‐fused post‐cranial material. Adult age classes are well represented in the dental AtD frequencies and were interpreted as the result of the slaughter of prime beef and retired lactating females. For calves aged less than 12 months, there was no statistical difference in the AtD frequencies based on dental and post‐cranial material indicating that the data is a good representation of the mortality patterns of calves, either natural or deliberate. At both sites there was a strong mortality peak at 3–6 months in all AtD profiles. At La Draga, this peak was clearly differentiated from a peak at 0–1 month, which can be interpreted neonatal mortality possible a consequence of the birthing season coinciding with the end of winter during more humid climatic conditions that at present. The deliberate slaughter peak around 3–6 months is discussed, and we propose that stock herders controlled the mortality of infant classes, possibly in response to variable external environment pressures while maintaining animal productivity. Copyright © 2014 John Wiley & Sons, Ltd.
Entheseal Changes in Free‐Ranging Versus Zoo Reindeer—Observing Activity Status of Reindeer
Authors: Niinimäki S. , Salmi A‐K.
Published: September 2014

We evaluate whether entheseal changes (EC) can be used to reconstruct activity among reindeer to study its domestication. Humans influence reindeer activity patterns through corralling, which renders them less mobile than free‐ranging reindeer and through use as draught animals, which can result in overuse of certain muscles. There is also variation within free‐ranging reindeer in baseline activity levels due to environmental factors. Other sources of variation at entheses include age, sex, pathology, size, and genetic disposition. Here we examine if there are differences in the entheses between zoo versus free‐ranging reindeer. We recorded the entheses of reindeer long bones using a modified EC scoring system. Weight effects were accounted for by performing analyses separately for specimens under and over 95 kg, but unfortunately age information was lacking. We found that several flexor muscle insertion sites in the ulna were more developed among free‐ranging reindeer. This difference is likely due to feeding behaviour. The free‐ranging animals were digging for lichen from under the snow whereas the zoo reindeer were fed by their keepers. This difference in entheses, however, was found to be significant only among the heavier reindeer. Among the zoo reindeer, the insertion for Subscapularis muscle was more developed, possibly due to increased time spent immobile with the shoulder‐bracing muscle apparatus activated. This difference was significant among the heavier deer and nearly statistically significant among the lighter weight reindeer. Domesticated Siberian draught reindeer fell between zoo and free‐ranging reindeer in several tibial entheses. According to these results, some forelimb entheses may be useful to study differences in mobility and feeding patterns between groups of reindeer. Copyright © 2014 John Wiley & Sons, Ltd.
A cross‐national comparison of 17 countries' insulin glargine drug labels
Authors: Polinski Jennifer M. , Kesselheim Aaron S. , Seeger John D. , Connolly John G. , Choudhry Niteesh K. , Shrank William H.
Published: September 2014

Purpose

Type 2 diabetes mellitus has reached epidemic proportions worldwide. Many patients with type 2 diabetes mellitus will require insulin, and the evidence‐based use of insulin is described in the prescription drug label. Product labels in different countries may provide inconsistent information. We evaluated the variability in drug label content for one brand of basal insulin across diverse settings.

Methods

We examined the drug label content pertinent to effective and safe use of insulin glargine across 17 countries: Abu Dhabi (United Arab Emirates), Argentina, Brazil, Canada, China, Germany, Israel, Italy, Japan, Mexico, Russia, Saudi Arabia, South Korea, Spain, Turkey, UK, and the USA. We compared label characteristics in settings where drug labels were governed by a local regulatory authority versus countries where labels were administered by a regional body or adopted from another locale.

Results

All 17 labels cautioned that providers should consider age, illness, diet, and exercise when prescribing. Only two (12%) described care of the fasting patient. Caution was urged for patients with renal or hepatic impairment in 16 (94%) labels. Four (24%) did not describe responses to missed doses, and five (29%) failed to recommend patient counseling about the risk of hypoglycemia. Labels emerging from regional or adopted regulatory bodies reported fewer patients in efficacy studies than did labels from settings with their own drug regulatory agencies (365 ± 0 patients vs. 3560 ± 2938, p = 0.04).

Conclusions

There is substantial variation in the content of drug labels for glargine, which may lead to international inconsistency in quality of care for diabetic patients. Copyright © 2014 John Wiley & Sons, Ltd.
Synthesis and characterization of biodegradable amphiphilic ABC Y‐shaped miktoarm terpolymer by click chemistry for drug delivery
Authors: Chu Yanfeng , Yu Huan , Zhang Yunti , Zhang Guangyan , Ma Yingying , Zhuo Renxi , Jiang Xulin
Published: September 2014

Biodegradable amphiphilic ABC Y‐shaped triblock copolymer (MPBC) containing PEG, PBLA, and PCL segments was synthesized via the combination of enzymatic ring‐opening polymerization (ROP) of epsilon‐caprolactone, ROP of BLA‐N‐carboxyanhydride and click chemistry, where PEG, PBLA, and PCL are poly(ethylene glycol), poly(benzyl‐l‐aspartate), and polycaprolactone, respectively. Propynylamine was employed as ROP initiator for the preparation of alkynyl‐terminated PBLA and methyloxy‐PEG with hydroxyl and azide groups at the chain‐end was used as enzymatic ROP initiator for synthesis of monoazido‐midfunctionalized block copolymer mPEG‐b‐PCL. The subsequent click reaction led to the formation of Y‐shaped asymmetric heteroarm terpolymer MPBC. The polymer structures were characterized by different analyses. The MPBC terpolymer self‐assembled into micelles and physically encapsulated drug doxorubicin (DOX) to form DOX‐loaded micelles, which showed good stability and slow drug release. In vitro cytotoxicity study indicated that the MPBC micelles were nontoxic and the DOX‐loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 3346–3355