bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: On the Scope of the Pt‐Catalyzed Srebnik Diborylation of Diazoalkanes. An Efficient Approach to Chiral Tertiary Boronic Esters and Alcohols via B‐Stabilized Carbanions.
Authors: Wommack Andrew J. , Kingsbury Jason S.
Published: September 2014

The formed geminal diboronic esters can be transformed to tertiary boronic esters, alcohols and stilbenes in good to excellent yields.
ChemInform Abstract: Arylphosphonylation and Arylazidation of Activated Alkenes.
Authors: Kong Wangqing , Merino Estibaliz , Nevado Cristina
Published: September 2014

Trisubstituted olefines are unreactive or decompose.
ChemInform Abstract: Synthesis of C2‐Methylene Glycitols from 1,2‐Cyclopropanated Sugars: En Route to Iminosugar Analogues.
Authors: Seshadri Kalapati , Sridhar Perali Ramu
Published: September 2014

Other diastereomers of (I) are converted to the corresponding stereoisomers of (VIII) in comparable yields.
ChemInform Abstract: Dimethyl Homophthalates to Naphthopyrans: The Total Synthesis of Arnottin I and the Formal Synthesis of (‐)‐Arnottin II.
Authors: Jangir Ravi , Argade Narshinha P.
Published: September 2014

Arnottin I is synthesized in three steps.
ChemInform Abstract: Stereoselective Total Synthesis of Ieodomycin C.
Authors: Tungen Joern E. , Aursnes Marius , Hansen Trond Vidar
Published: September 2014

The synthesis of the antibacterial ieodomycin C (I) and its enantiomer is achieved.
ChemInform Abstract: Myrotheciumones: Bicyclic Cytotoxic Lactones Isolated from an Endophytic Fungus of Ajuga decumbens.
Authors: Lin Ting , Wang Guanghui , Shan Wenjun , Zeng Dequan , Ding Rong , Jiang Xin , Zhu Dan , Liu Xiaoxuan , Yang Shuiyuan , Chen Haifeng
Published: September 2014

The bicyclic lactones, myrotheciumones A (I) and B (II), possessing a rare ring‐fusion system are isolated from the secondary metabolites of M.
ChemInform Abstract: Synthetic and Biological Studies of Phaeosphaerides.
Authors: Chatzimpaloglou Anthoula , Kolosov Mikhail , Eckols T. Kris , Tweardy David J. , Sarli Vasiliki
Published: September 2014

The first total syntheses of phaeosphaeride B (I) and an unnatural phaeosphaeride are reported.
ChemInform Abstract: Ultra‐Strong and Low‐Density Nanotubular Bulk Materials with Tunable Feature Sizes.
Authors: Biener Monika M. , Ye Jianchao , Baumann Theodore F. , Wang Y. Morris , Shin Swanee J. , Biener Juergen , Hamza Alex V.
Published: September 2014

Ultralow‐density, ultra‐high suface area Al2O3 and TiO2 bulk materials with interconnected nanotubular morphology are synthesized.
ChemInform Abstract: Routes to Tin Chalcogenide Materials as Thin Films or Nanoparticles: A Potentially Important Class of Semiconductor for Sustainable Solar Energy Conversion
Authors: Lewis David J. , Kevin Punarja , Bakr Osman , Muryn Christopher A. , Malik Mohammad Azad , O'Brien Paul
Published: September 2014

Review: 113 refs.
ChemInform Abstract: Coordination Chemistry of Schiff Base Tin Complexes
Authors: Manju Manju , Mishra Neelima , Kumar D.
Published: September 2014

Review: 132 refs.
ChemInform Abstract: Molecular Metal Catalysts on Supports: Organometallic Chemistry Meets Surface Science
Authors: Serna Pedro , Gates Bruce C.
Published: September 2014

Review: 36 refs.
ChemInform Abstract: Solid‐Phase Peptide Synthesis (SPPS), C‐Terminal vs. Side‐Chain Anchoring: A Reality or a Myth
Authors: Cherkupally Prabhakar , Acosta Gerardo A. , Ramesh Suhas , De la Torre Beatriz G. , Govender Thavendran , Kruger Hendrik G. , Albericio Fernando
Published: September 2014

Review: 75 refs.
ChemInform Abstract: Stereoselective Bromofunctionalization of Alkenes
Authors: Tan Chong Kiat , Yu Wesley Zongrong , Yeung Ying‐Yeung
Published: September 2014

Review: 140 refs.
ChemInform Abstract: Microwave‐Assisted Synthesis of Seven‐ and Higher‐Membered N‐Heterocycles
Authors: Kaur Navjeet , Kishore Dharma
Published: September 2014

Review: [114 refs.
ChemInform Abstract: Use of Ionic Liquids as Neoteric Solvents in the Synthesis of Fused Heterocycles
Authors: Nevagi Reshma J. , Dighe Santosh N. , Dighe Satish N. , Chaskar Pratip K. , Srinivasan Kumar V. , Jain Kishor S.
Published: September 2014

Review: [125 refs.
ChemInform Abstract: Dynamic Kinetic Resolution of Racemic Allylic Alcohols via Hydrolase—Metal Combo Catalysis: An Effective Method for the Synthesis of Optically Active Compounds
Authors: Akai Shuji
Published: September 2014

Review: [41 refs.
ChemInform Abstract: Key Processes in Ruthenium‐Catalyzed Olefin Metathesis
Authors: Nelson David J. , Manzini Simone , Urbina‐Blanco Cesar A. , Nolan Steven P.
Published: September 2014

Review: 172 refs.
ChemInform Abstract: Recent Advances in Heterobimetallic Palladium(II)/Copper(II) Catalyzed Domino Difunctionalization of Carbon—Carbon Multiple Bonds
Authors: Beccalli Egle M. , Broggini Gianluigi , Gazzola Silvia , Mazza Alberto
Published: September 2014

Review: [83 refs.
ChemInform Abstract: Stereoselectively Fluorinated N‐Heterocycles: A Brief Survey
Authors: Hu Xiang‐Guo , Hunter Luke
Published: September 2014

Review: 78 refs.
ChemInform Abstract: Three‐Membered Ring Systems
Authors: Bergmeier Stephen C. , Lapinsky David J.
Published: September 2014

Review: advances in the synthesis and reactions of epoxides and aziridines published i2012; 143 refs.
ChemInform Abstract: Cobalt Mediated C‐H Bond Functionalization: Emerging Tools for Organic Synthesis
Authors: Tilly David , Dayaker Gandrath , Bachu Prabhakar
Published: September 2014

Review: 170 refs.
ChemInform Abstract: Theoretical Treatment of One Electron Redox Transformation of a Small Molecule Using F‐Element Complexes
Authors: Castro Ludovic , Kefalidis Christos E. , McKay David , Essafi Stephanie , Perrin Lionel , Maron Laurent
Published: September 2014

Review: 62 refs.
ChemInform Abstract: Electrode Materials and Electrode‐Oxide Interfaces in Semiconductor Gas Sensors
Authors: Lee S. P.
Published: September 2014

Review: 80 refs.
ChemInform Abstract: Pancake Bonds: π‐Stacked Dimers of Organic and Light‐Atom Radicals
Authors: Preuss Kathryn E.
Published: September 2014

Review: 181 refs.
ChemInform Abstract: Affinity‐Based Target Identification for Bioactive Small Molecules
Authors: Kawatani Makoto , Osada Hiroyuki
Published: September 2014

Review: 111 refs.
ChemInform Abstract: A Global Perspective on a Review of a Three‐Year C‐Nucleosides Development: 2009‐2011
Authors: El‐Atawy Mohamed A. , Abd Al‐Moaty Mohamed Nabil , Amer Adel
Published: September 2014

Review: 33 refs.
ChemInform Abstract: Nanostructured Electrochromic Smart Windows: Traditional Materials and NIR‐Selective Plasmonic Nanocrystals
Authors: Runnerstrom Evan L. , Llordes Anna , Lounis Sebastien D. , Milliron Delia J.
Published: September 2014

Review: 93 refs.
ChemInform Abstract: Acentric and Chiral Heterometallic Inorganic‐Organic Hybrid Frameworks Mediated by Alkali or Alkaline Earth Ions: Synthesis and NLO Properties
Authors: Tian Chongbin , Zhang Huabin , Du Shaowu
Published: September 2014

Review: 94 refs.
ChemInform Abstract: On‐line Preconcentration in Capillary Electrophoresis for Analysis of Agrochemical Residues
Authors: Fang Rou , Yi Ling‐Xiao , Shao Yu‐Xiu , Zhang Li , Chen Guan‐Hua
Published: September 2014

Review: 175 refs.
Benzofuran–Chalcone Hybrids as Potential Multifunctional Agents against Alzheimer’s Disease: Synthesis and in vivo Studies with Transgenic Caenorhabditis elegans
Authors: Sashidhara Koneni V. , Modukuri Ram K. , Jadiya Pooja , Dodda Ranga Prasad , Kumar Manoj , Sridhar Balasubramaniam , Kumar Vikash , Haque Rizwanul , Siddiqi Mohammad Imran , Nazir Aamir
Published: September 2014

In the search for effective multifunctional agents for the treatment of Alzheimer’s disease (AD), a series of novel hybrids incorporating benzofuran and chalcone fragments were designed and synthesized. These hybrids were screened by using a transgenic Caenorhabditis elegans model that expresses the human β‐amyloid (Aβ) peptide. Among the hybrids investigated, (E)‐3‐(7‐methyl‐2‐(4‐methylbenzoyl)benzofuran‐5‐yl)‐1‐phenylprop‐2‐en‐1‐one (4 f), (E)‐3‐(2‐benzoyl‐7‐methylbenzofuran‐5‐yl)‐1‐phenylprop‐2‐en‐1‐one (4 i), and (E)‐3‐(2‐benzoyl‐7‐methylbenzofuran‐5‐yl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one (4 m) significantly decreased Aβ aggregation and increased acetylcholine (ACh) levels along with the overall availability of ACh at the synaptic junction. These compounds were also found to decrease acetylcholinesterase (AChE) levels, reduce oxidative stress in the worms, lower lipid content, and to provide protection against chemically induced cholinergic neurodegeneration. Overall, the multifunctional effects of these hybrids qualify them as potential drug leads for further development in AD therapy.
A continuum model for platelet plug formation, growth and deformation
Authors: Storti F. , van de Vosse F. N.
Published: September 2014

A numerical framework for modelling platelet plug dynamics is presented in this work. It consists of an extension of a biochemical and plug growth model with a solid mechanics model for the plug coupled with a fluid–structure interaction model for the blood flow–plug system. The platelet plug is treated as a neo‐Hookean elastic solid, of which the implementation is based on an updated Lagrangian approach. The framework is applied to different haemodynamic configurations coupled with different shear moduli of the plug. Results about plug growth, shape and size, as well as the stress distribution, are shown. Based on the simulations performed, we conclude that the deformability of the platelet plug is essential for its growth. Copyright © 2014 John Wiley & Sons, Ltd.
Protocol for Rational Design of Covalently Interacting Inhibitors
Authors: Schmidt Thomas C. , Welker Armin , Rieger Max , Sahu Prabhat K. , Sotriffer Christoph A. , Schirmeister Tanja , Engels Bernd
Published: September 2014

The inhibition potencies of covalent inhibitors mainly result from the formation of a covalent bond to the enzyme during the inhibition mechanism. This class of inhibitors has essentially been ignored in previous target‐directed drug discovery projects because of concerns about possible side effects. However, their advantages, such as higher binding energies and longer drug‐target residence times moved them into the focus of recent investigations. While the rational design of non‐covalent inhibitors became standard the corresponding design of covalent inhibitors is still in its early stages. Potent covalent inhibitors can be retrieved from large compound libraries by covalent docking approaches but protocols are missing that can reliably predict the influence of variations in the substitution pattern on the affinity and/or reactivity of a given covalent inhibitor. Hence, the wanted property profile can only be obtained from trial‐and‐error proceedings. This paper presents an appropriate protocol which is able to predict improved covalent inhibitors. It uses hybrid approaches, which mix quantum mechanical (QM) and molecular mechanical (MM) methods to predict variations in the reactivity of the inhibitor. They are also used to compute the required information about the non‐covalent enzyme–inhibitor complex. Docking tools are employed to improve the inhibitor with respect to the non‐covalent interactions formed in the binding site.
Two 3D Coordination Frameworks Based on Benzobisimidazole Linkers Generated under Similar Conditions: Synthesis, Structures and Thermal Properties
Authors: Biswas Shyam , Liu Ying‐Ya , Tonigold Markus , Weil Matthias , Volkmer Dirk
Published: September 2014

Herein, we present two benzobisimidazole‐based 3D open coordination framework structures. Single‐crystal X‐ray analyses reveal that the title compounds [Zn(H2‐BBIM)(SO4)]·DMSO (1) (H2‐BBIM = benzobisimidazole; DMSO = dimethyl sulfoxide) and [Co(H2‐BBIM)(SO4)(DMSO)0.5] (2) possess two different framework structures, although both of them have been synthesized under similar conditions. Compounds 1 and 2 exhibit cubic diamondoid and tetragonal CrB4 topological nets, respectively, in which the four‐connected tetrahedral {MN2O2} (MII = Zn, Co) coordination units are located at the vertices and the edges are occupied by H2‐BBIM ligands and sulfate anions. Only tetracoordination is observed in 1, whereas both tetra‐ and pentacoordination is present in 2. The phase purity of the compounds was ascertained by X‐ray powder diffraction (XRPD) analysis, infrared spectroscopy, and elemental analysis. Variable‐temperature XRPD analysis indicated that 1 and 2 are stable up to 90 and 140 °C, respectively.
Iodine‐Mediated Oxidation of Ynamides: A Facile Access to N‐Monosubstituted α‐Ketoamides and α‐Ketoimides
Authors: Huang Hai , He Guangke , Zhu Xiaolin , Jin Xiaodong , Qiu Shineng , Zhu Hongjun
Published: September 2014

An efficient iodine‐mediated oxidation reaction for ynamides has been developed to produce N‐monosubstituted α‐ketoamides and α‐ketoimides. This oxidative method, which exhibits good functional group tolerance, was performed under mild conditions without a metal catalyst.
A Versatile and Efficient Palladium–meta‐Terarylphosphine Catalyst for the Copper‐Free Sonogashira Coupling of (Hetero‐)Aryl Chlorides and Alkynes
Authors: Yang Yong , Chew Xinying , Johannes Charles W. , Robins Edward G. , Jong Howard , Lim Yee Hwee
Published: September 2014

A novel meta‐terarylphosphine ligand, Cy*Phine, was developed and found to be a highly active promoter of copper‐free Sonogashira cross‐coupling reactions when combined in situ with a palladium source. The evolutionary m‐terarylphosphine ligand architecture was able to impose significant performance advantages over its biarylphosphine congeners. An expedient and versatile protocol was also devised with an emphasis on substrates applicable to the fine‐chemicals industry by featuring a diverse range of challenging, electron‐rich aryl chlorides and terminal alkynes. The Pd–Cy*Phine catalyst was able to deliver products in excellent yields with efficient substrate utilization, which minimizes the generation of commonly formed byproducts, and the reaction is tolerant of a variety of substrates with unprotected functional groups.
High‐Yielding Total Synthesis of Sexually Deceptive Chiloglottones and Antimicrobial Dialkylresorcinols through an Organocatalytic Reductive Coupling Reaction
Authors: Madhavachary Rudrakshula , Ramachary Dhevalapally B.
Published: September 2014

Biologically important, less‐explored natural products of sexually deceptive chiloglottones, antimicrobial dialkylresorcinols, and their many analogues were synthesized in very good yields in a sequential two‐pot manner by using an “organocatalytic reductive coupling reaction” as the key step.
Ordered Mesoporous Carbon and Thiolated Polyaniline Modified Electrode for Simultaneous Determination of Cadmium(II) and Lead(II) by Anodic Stripping Voltammetry
Authors: Tang Lin , Chen Jun , Zeng Guangming , Zhu Yuan , Zhang Yi , Zhou Yaoyu , Xie Xia , Yang Guide , Zhang Sheng
Published: September 2014

The fabrication and evaluation of a glassy carbon electrode (GCE) modified with ordered mesoporous carbon (OMC), 2‐mercaptoethanesulfonate (MES)‐tethered polyaniline (PANI) and bismuth for simultaneous determination of trace Cd2+ and Pb2+ by differential pulse anodic stripping voltammetry (DPASV) are presented here. The morphology and electrochemical properties of the fabricated electrode were respectively characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Experimental parameters such as PANI disposition, preconcentration potential, preconcentration time and bismuth concentration were optimized. Under optimum conditions, the fabricated electrode exhibited linear calibration curves ranged from 1 to 120 nM for Cd2+ and Pb2+. The limits of detection (LOD) were 0.26 nM for Cd2+ and 0.16 nM for Pb2+ (S/N=3), respectively. Additionally, repeatability, reproducibility, interference and application were also investigated, and the proposed electrode exhibited excellent performance. The proposed method could be extended for the development of other new sensors for heavy metal determination.
Improving cold‐flow properties of biodiesel through blending with nonedible castor oil methyl ester
Authors: Ghanei Rouhollah
Published: September 2014

Castor oil biodiesel is one of the different types of renewable fuels which can be produced from nonedible source. The unique physical properties of this fuel including low cloud point (CP) and pour point (PP) will bring about opportunities to improve the cold‐flow properties of other fuels. Biodiesel was first synthesized from castor, canola, and frying oil with purity of 98.8%, 97.9%, and 98.5%, respectively. Blends of castor biodiesel with other biodiesels and conventional diesel were prepared in six various levels. Kinematic viscosity, specific gravity, CP, and PP of all samples were then evaluated. In addition, maximum acceptable ratio of castor biodiesel in blends of conventional diesel, canola biodiesel, and frying oil biodiesel were obtained and equal to 48, 35, and 50 wt %, respectively. At such condition, an improvement of 6.5, 4.5, and 12.5°C for CP were observed. Moreover, although other properties were in the ranges of ASTM, an enhancement of 7, 7, and 15°C for PP were obtained. © 2014 American Institute of Chemical Engineers Environ Prog, 34: 897–902, 2015
Alternate bars in a sandy gravel bed river: generation, migration and interactions with superimposed dunes
Authors: Rodrigues Stephane , Mosselman Erik , Claude Nicolas , Wintenberger Coraline L. , Juge Philippe
Published: September 2014

A field study was carried out to investigate the development of alternate bars in a secondary channel of the Loire River (France) as a function of discharge variations. We combined frequent bathymetric surveys, scour chains and stratigraphical analysis of deposits with measurements and modelling of flow dynamics. The channel exhibited migrating bars, non‐migrating bars and superimposed dunes. Possible mechanisms of bar initiation were found to be chutes associated with changes of bank direction and instability resulting from interactions between existing bars during the fall in water level after floods. We propose that the reworking of bar sediments during low flows (high width‐to‐depth ratio β), reinforced by high values of the Shields mobility parameter, can explain the formation or re‐generation of new alternate migrating bars during a subsequent flood. The migration pattern of the bars was found to be cyclic and to depend mainly on (i) channel layout and (ii) the dynamics of superimposed dunes with heights and lengths depending on location and discharge value. For instance, the hysteresis affecting the steepness of dunes influences the flow resistance of the dunes as well as the celerity of migrating bars during flood events. We compare the findings from the field with results from theoretical studies on alternate bars. This gives insight in the phenomena occurring in the complex setting of real rivers, but it also sheds light on the extent to which bar theories based on idealized cases can predict those phenomena. Copyright © 2014 John Wiley & Sons, Ltd.
RNA‐sequencing reveals oligodendrocyte and neuronal transcripts in microglia relevant to central nervous system disease
Authors: Solga Anne C. , Pong Winnie W. , Walker Jason , Wylie Todd , Magrini Vincent , Apicelli Anthony J. , Griffith Malachi , Griffith Obi L. , Kohsaka Shinichi , Wu Gregory F. , Brody David L. , Mardis Elaine R. , Gutmann David H.
Published: September 2014

Expression profiling of distinct central nervous system (CNS) cell populations has been employed to facilitate disease classification and to provide insights into the molecular basis of brain pathology. One important cell type implicated in a wide variety of CNS disease states is the resident brain macrophage (microglia). In these studies, microglia are often isolated from dissociated brain tissue by flow sorting procedures [fluorescence‐activated cell sorting (FACS)] or from postnatal glial cultures by mechanic isolation. Given the highly dynamic and state‐dependent functions of these cells, the use of FACS or short‐term culture methods may not accurately capture the biology of brain microglia. In the current study, we performed RNA‐sequencing using Cx3cr1+/GFP labeled microglia isolated from the brainstem of 6‐week‐old mice to compare the transcriptomes of FACS‐sorted versus laser capture microdissection (LCM). While both isolation techniques resulted in a large number of shared (common) transcripts, we identified transcripts unique to FACS‐isolated and LCM‐captured microglia. In particular, ∼50% of these LCM‐isolated microglial transcripts represented genes typically associated with neurons and glia. While these transcripts clearly localized to microglia using complementary methods, they were not translated into protein. Following the induction of murine experimental autoimmune encephalomyelitis, increased oligodendrocyte and neuronal transcripts were detected in microglia, while only the myelin basic protein oligodendrocyte transcript was increased in microglia after traumatic brain injury. Collectively, these findings have implications for the design and interpretation of microglia transcriptome‐based investigations. GLIA 2015;63:531–548
Cardiac dysfunction associated with a nucleotide polymerase inhibitor for treatment of hepatitis C
Authors: Ahmad Tariq , Yin Philip , Saffitz Jeffrey , Pockros Paul J. , Lalezari Jacob , Shiffman Mitchell , Freilich Bradley , Zamparo Joann , Brown Kyle , Dimitrova Dessislava , Kumar Monica , Manion Doug , Heath‐Chiozzi Margo , Wolf Robert , Hughes Eric , Muir Andrew J. , Hernandez Adrian F.
Published: September 2014

Treatment for chronic hepatitis C virus (HCV) infection is evolving from interferon (IFN)‐based therapy to direct‐acting antiviral (DAA) agents, yet some safety concerns have arisen involving cardiac toxicity. In this study, we sought to better understand the potential off‐target toxicities of new DAAs. We retrospectively evaluated the clinical and pathological findings of the sentinel case in a phase II study that led to clinical development discontinuation for BMS‐986094, an HCV nucleotide polymerase (nonstructural 5B) inhibitor. We also report on outcomes from other patients in the same study, including electrocardiogram changes, cardiovascular biomarkers, and transthoracic echocardiograms. Thirty‐four patients received IFN‐free BMS‐986094 regimens. Six patients had left ventricular ejection fractions (LVEFs) <30%, 8 had LVEFs 30%‐50%, and 11 required hospitalization for suspected cardiotoxicity. Of the patients with LVEF <50%, 6 had normalization of systolic function after a median of 20 days. T‐wave inversions were the most sensitive predictor of LVEF dysfunction. B‐type natriuretic peptide levels increased over time and correlated with the degree of LVEF dysfunction. Pathological analysis of cardiac tissue revealed severe myocyte damage with elongated myofibrils without gross necrosis. These findings were consistent with some results of recent primate studies that were conducted to further investigate the potential mechanisms of BMS‐986094 toxicity. Conclusion: A novel nucleotide analog polymerase inhibitor developed for HCV treatment may cause a toxic cardiomyopathy. Ongoing surveillance of DAAs for cardiotoxicities may be beneficial, especially among patients at higher risk for cardiovascular disease. (Hepatology 2015;62:409–416
Anthropometric factors and ovarian cancer risk: A systematic review and nonlinear dose‐response meta‐analysis of prospective studies
Authors: Aune Dagfinn , Navarro Rosenblatt Deborah A. , Chan Doris Sau Man , Abar Leila , Vingeliene Snieguole , Vieira Ana Rita , Greenwood Darren C. , Norat Teresa
Published: September 2014

In the World Cancer Research Fund/American Institute for Cancer Research report from 2007 the evidence relating body fatness to ovarian cancer risk was considered inconclusive, while the evidence supported a probably causal relationship between adult attained height and increased risk. Several additional cohort studies have since been published, and therefore we conducted an updated meta‐analysis of the evidence as part of the Continuous Update Project. We searched PubMed and several other databases up to 20th of August 2014. Summary relative risks (RRs) were calculated using a random effects model. The summary relative risk for a 5‐U increment in BMI was 1.07 (95% CI: 1.03–1.11, I2 = 54%, n = 28 studies). There was evidence of a nonlinear association, pnonlinearity < 0.0001, with risk increasing significantly from BMI∼28 and above. The summary RR per 5 U increase in BMI in early adulthood was 1.12 (95% CI: 1.05–1.20, I2 = 0%, pheterogeneity= 0.54, n = 6), per 5 kg increase in body weight was 1.03 (95% CI: 1.02–1.05, I2 = 0%, n = 4) and per 10 cm increase in waist circumference was 1.06 (95% CI: 1.00–1.12, I2 = 0%, n = 6). No association was found for weight gain, hip circumference or waist‐to‐hip ratio. The summary RR per 10 cm increase in height was 1.16 (95% CI: 1.11–1.21, I2 = 32%, n = 16). In conclusion, greater body fatness as measured by body mass index and weight are positively associated risk of ovarian cancer, and in addition, greater height is associated with increased risk. Further studies are needed to clarify whether abdominal fatness and weight gain is associated with risk.
Multidimensional Permanents and an Upper Bound on the Number of Transversals in Latin Squares
Authors: Taranenko A. A.
Published: September 2014

The permanent of a multidimensional matrix is the sum of products of entries over all diagonals. A nonnegative matrix whose every 1‐dimensional plane sums to 1 is called polystochastic. A latin square of order n is an array of n symbols in which each symbol occurs exactly once in each row and each column. A transversal of such a square is a set of n entries such that no two entries share the same row, column, or symbol. Let T(n) be the maximum number of transversals over all latin squares of order n. Here, we prove that over the set of multidimensional polystochastic matrices of order n the permanent has a local extremum at the uniform matrix for whose every entry is equal to . Also, we obtain an asymptotic value of the maximal permanent for a certain set of nonnegative multidimensional matrices. In particular, we get that the maximal permanent of polystochastic matrices is asymptotically equal to the permanent of the uniform matrix, whence as a corollary we have an upper bound on the number of transversals in latin squares

urn:x-wiley:10638539:media:jcd21413:jcd21413-math-0003
Lkb1 Deletion Promotes Ectopic Lipid Accumulation in Muscle Progenitor Cells and Mature Muscles
Authors: Shan Tizhong , Zhang Pengpeng , Bi Pengpeng , Kuang Shihuan
Published: September 2014

Excessive intramyocellular triglycerides (muscle lipids) are associated with reduced contractile function, insulin resistance, and Type 2 diabetes, but what governs lipid accumulation in muscle is unclear. Here we report a role of Lkb1 in regulating lipid metabolism in muscle stem cells and their descendent mature muscles. We used MyodCre and Lkb1flox/flox mice to specifically delete Lkb1 in myogenic cells including stem and differentiated cells, and examined the lipid accumulation and gene expression of myoblasts cultured from muscle stem cells (satellite cells). Genetic deletion of Lkb1 in myogenic progenitors led to elevated expression of lipogenic genes and ectopic lipid accumulation in proliferating myoblasts. Interestingly, the Lkb1‐deficient myoblasts differentiated into adipocyte‐like cells upon adipogenic induction. However, these adipocyte‐like cells maintained myogenic gene expression with reduced ability to form myotubes efficiently. Activation of AMPK by AICAR prevented ectopic lipid formation in the Lkb1‐null myoblasts. Notably, Lkb1‐deficient muscles accumulated excessive lipids in vivo in response to high‐fat diet feeding. These results demonstrate that Lkb1 acts through AMPK to limit lipid deposition in muscle stem cells and their derivative mature muscles, and point to the possibility of controlling muscle lipid content using AMPK activating drugs. J. Cell. Physiol. 230: 1033–1041, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Effect of modification of citraconic anhydrides on catalytic activity and thermostability of enzymes
Authors: Matsumoto Michiaki , Nakagawa Takashi , Uchida Yosuke , Seki Kumiko , Ohba Masayoshi , Kondo Kazuo
Published: September 2014

BACKGROUND

Activation and stabilization of enzymes have received considerable attention. In recent years, chemical modification has re‐emerged as a powerful complementary approach to site‐directed mutagenesis and directed evolution because it is simple and effective. Chemical modification of enzymes by dicarboxylic acid anhydride enhanced their activities and stabilities.

RESULTS

Lipase, α‐chymotrypsin and subtilisin modified by citraconic anhydride were examined. Lipase and α‐chymotrypsin were successfully modified by citraconic anhydride, while subtilisin showed poor reactivity with it. Optimum pH range for lipase and α‐chymotrypsin, and the secondary structure of α‐chymotrypsin was found to be unchanged by the modification process. Effect of the modification on the activity and thermostability of lipase was small. On the other hand, modification of lysine residues on the enzyme surface enhanced the catalytic activity and thermostability of α‐chymotrypsin. Further modification of lysine residues caused the reduction of thermostability. Modification of more hydrophobic dicarboxylic acid anhydride resulted in an increase in thermostability.

CONCLUSION

The modification of the lysine residues on the enzyme surface with citraconic anhydride shows a small effect on the catalytic reactivity and enhances the thermostability of the enzymes. © 2014 Society of Chemical Industry
Glial response in the rat models of functionally distinct cholinergic neuronal denervations
Authors: Bataveljic Danijela , Petrovic Jelena , Lazic Katarina , Saponjic Jasna , Andjus Pavle
Published: September 2014

Alzheimer's disease (AD) involves selective loss of basal forebrain cholinergic neurons, particularly in the nucleus basalis (NB). Similarly, Parkinson's disease (PD) might involve the selective loss of pedunculopontine tegmental nucleus (PPT) cholinergic neurons. Therefore, lesions of these functionally distinct cholinergic centers in rats might serve as models of AD and PD cholinergic neuropathologies. Our previous articles described dissimilar sleep/wake‐state disorders in rat models of AD and PD cholinergic neuropathologies. This study further examines astroglial and microglial responses as underlying pathologies in these distinct sleep disorders. Unilateral lesions of the NB or the PPT were induced with rats under ketamine/diazepam anesthesia (50 mg/kg i.p.) by using stereotaxically guided microinfusion of the excitotoxin ibotenic acid (IBO). Twenty‐one days after the lesion, loss of cholinergic neurons was quantified by nicotinamide adenine dinucleotide phosphate‐diaphorase histochemistry, and the astroglial and microglial responses were quantified by glia fibrillary acidic protein/OX42 immunohistochemistry. This study demonstrates, for the first time, the anatomofunctionally related astroglial response following unilateral excitotoxic PPT cholinergic neuronal lesion. Whereas IBO NB and PPT lesions similarly enhanced local astroglial and microglial responses, astrogliosis in the PPT was followed by a remote astrogliosis within the ipslilateral NB. Conversely, there was no microglial response within the NB after PPT lesions. Our results reveal the rostrorostral PPT‐NB astrogliosis after denervation of cholinergic neurons in the PPT. This hierarchically and anatomofunctionally guided PPT‐NB astrogliosis emerged following cholinergic neuronal loss greater than 17% throughout the overall rostrocaudal PPT dimension. © 2014 Wiley Periodicals, Inc.
Astrocytic exportin‐7 responds to ischemia through mediating LKB1 translocation from the nucleus to the cytoplasm
Authors: Liang Hai Jie , Chai Rui Chao , Li Xi , Kong Jin Ge , Jiang Jiao Hua , Ma Ju , Vatcher Greg , Yu Albert Cheung Hoi
Published: September 2014

The superfamily of importin‐β–related proteins is the largest class of nuclear transport receptors and can be generally divided into importins and exportins according to their transport directions. Eleven importins and seven exportins have been identified, and the expression patterns of both classes are important for their functions in nucleocytoplasmic transport activities. This study demonstrates that all of the importins (importin‐β; transportin‐1, ‐2, and ‐3; and importin‐4, ‐5, ‐7, ‐8, ‐9, ‐11, and ‐13) and all the exportins (exportin‐1, ‐2, ‐4, ‐5, ‐6, ‐7, and ‐t) are differentially expressed in the cerebral cortex, cerebellum, hippocampus, and brainstem and in primary cultures of cerebral cortical astrocytes and neurons. For astrocytes, we observed that different importins and exportins displayed different expression changes during 0–6 hr of ischemia treatment, especially an increase of both the mRNA and the protein of exportin‐7. Immunostaining showed that exportin‐7 accumulated inside the nucleus and around the nuclear envelope. In addition, we noticed an increased cytoplasmic distribution of one of the cargo proteins of exportin‐7, LKB1, an important element in maintaining energy homeostasis. This increased cytoplasmic distribution was accompanied by an increased expression of exportin‐7 under ischemia in astrocytes. We demonstrate that exportin‐7 responds to ischemia in astrocytes and that this response involves translocation of LKB1, a protein that plays important roles during metabolic stress, from the nucleus to the cytoplasm. © 2014 Wiley Periodicals, Inc.
Projected changes in precipitation intensity and frequency in Switzerland: a multi‐model perspective
Authors: Fischer A. M. , Keller D. E. , Liniger M. A. , Rajczak J. , Schär C. , Appenzeller C.
Published: September 2014

Fundamental changes in the hydrological cycle are to be expected in a future warmer climate. For Switzerland, recent climate change assessments based on the ENSEMBLES regional climate models project for the A1B emission scenario summer mean precipitation to significantly decrease by the end of this century, whereas winter mean precipitation tend to rise in Southern Switzerland. From an end‐user perspective, projected changes in seasonal means are often insufficient to adequately address the multifaceted challenges of climate change adaptation. In this study, we investigate the projected changes in seasonal precipitation by considering changes in frequency and intensity, precipitation type (convective vs stratiform) and temporal structure (wet and dry spells) over Switzerland. As proxies for rain‐type changes, we rely on the parameterized convective and large‐scale precipitation components simulated by the models. The study reveals that the projected summer drying over Switzerland at the end of the century is mainly driven by a widespread reduction in the number of precipitation days. Thereby, the drying evolves altitude‐specific: over low‐land regions it is associated with a decrease in both convective and large‐scale precipitation. Over elevated regions it is primarily associated with a decline in large‐scale precipitation only, whereas convective precipitation remains at current levels. As a consequence, almost all the models project an increase in convective fraction at elevated altitudes. The decrease in the number of wet days during summer is accompanied by decreases (increases) in the number of multi‐day wet (dry) spells. This future shift in multi‐day episodes also lowers down the likelihood of short dry spell occurrence in all of the models. The models further project a higher mean precipitation intensity in spring and autumn north of the Alps, whereas a similar tendency is expected for the winter season over most of Switzerland.
SERS spectrum of the peptide thymosin‐β4 obtained with Ag nanorod substrate
Authors: Meshik Xenia , Wu Xiaomeng , Zhao Yiping , Schwartz Joel , Dutta Mitra , Stroscio Michael
Published: September 2014

Thymosin‐β4 is a peptide found at high concentrations in a wide range of mammalian cells. It has been shown to be elevated in metastatic cells. In this study, the surface‐enhanced Raman spectrum of thymosin‐β4 was obtained using a silver nanorod array surface‐enhanced Raman scattering substrate. Significant Raman peaks were found, and the corresponding vibrational modes were assigned based on previously published literature, with amide A–B, amide I, and amide III modes all identified. The majority of the remaining peaks were assigned modes based on the spectra of lysine and glutamic acid, the two most abundant amino acids in the thymosin‐β4 sequence. A standard Raman spectrum of thymosin‐β4 was also obtained and analyzed for comparison. Because thymosin‐β4 plays a significant role in regulating the formation of cellular cytoskeleton and other several biological processes, its Raman spectrum will be of use to researchers. Copyright © 2014 John Wiley & Sons, Ltd.
Validation and application of modeling algorithms for the design of molecularly imprinted polymers
Authors: Liu Bing , Ou Lulu , Zhang Fuyuan , Zhang Zhijun , Li Hongying , Zhu Mengyu , Wang Shuo
Published: September 2014

In the study, four different semiempirical algorithms, modified neglect of diatomic overlap, a reparameterization of Austin Model 1, complete neglect of differential overlap and typed neglect of differential overlap, have been applied for the energy optimization of template, monomer, and template‐monomer complexes of imprinted polymers. For phosmet‐, estrone‐, and metolcarb‐imprinted polymers, the binding energies of template‐monomer complexes were calculated and the docking configures were assessed in different molar ratio of template/monomer. It was found that two algorithms were not suitable for calculating the binding energy in template‐monomers complex system. For the other algorithms, the obtained optimum molar ratio of template and monomers were consistent with the experimental results. Therefore, two algorithms have been selected and applied for the preparation of enrofloxacin‐imprinted polymers. Meanwhile using a different molar ratio of template and monomer, we prepared imprinted polymers and nonimprinted polymers, and evaluated the adsorption to template. It was verified that the experimental results were in good agreement with the modeling results. As a result, the semiempirical algorithm had certain feasibility in designing the preparation of imprinted polymers.
Ring‐Opening Metathesis Polymerization of 18‐e Cobalt(I)‐Containing Norbornene and Application as Heterogeneous Macromolecular Catalyst in Atom Transfer Radical Polymerization
Authors: Yan Yi , Zhang Jiuyang , Wilbon Perry , Qiao Yali , Tang Chuanbing
Published: September 2014

In the last decades, metallopolymers have received great attention due to their various applications in the fields of materials and chemistry. In this article, a neutral 18‐electron exo‐substituted η4‐cyclopentadiene CpCo(I) unit‐containing polymer is prepared in a controlled/“living” fashion by combining facile click chemistry and ring‐opening meta­thesis polymerization (ROMP). This Co(I)‐containing polymer is further used as a heterogeneous macromolecular catalyst for atom transfer radical polymerization (ATRP) of methyl methacrylate and styrene.

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Growth plate abnormalities in pediatric cancer patients undergoing phase 1 anti‐angiogenic therapy: A report from the children's oncology group phase I consortium
Authors: Voss Stephan D. , Glade‐Bender Julia , Spunt Sheri L. , DuBois Steven G. , Widemann Brigitte C. , Park Julie R. , Leary Sarah E. S. , Nelson Marvin D. , Adamson Peter C. , Blaney Susan M. , Weigel Brenda
Published: September 2014

Background

Pre‐clinical studies suggest that anti‐angiogenic agents may be toxic to the developing growth plate. The purpose of this study was to evaluate the incidence of growth plate abnormalities in children with refractory cancer undergoing anti‐angiogenic therapy.

Procedure

Targeted radiographic studies from 53 subjects enrolled on six separate Children's Oncology Group Phase 1 and Pilot Consortium clinical trials evaluating new anti‐cancer agents interfering with angiogenesis were reviewed. Subjects received tyrosine kinase inhibitors with anti‐angiogenic effects (n = 35), monoclonal antibodies targeting vascular endothelial growth factor (VEGF) (n = 13), or angiopoietin (n = 5). Radiographs of their distal femur/proximal tibia were obtained at baseline. Follow‐up radiographs were obtained after odd‐numbered treatment cycles in patients with open growth plates who did not experience disease progression prior to cycle 3.

Results

Baseline and follow‐up growth plate radiographs were acquired in 48/53 (90%) of patients. Five patients (9.4%), all of whom received a specific VEGF/VEGFR blocking agent (sunitinib [n = 1] or pazopanib [n = 4]), had growth plate abnormalities. Four patients had growth plate widening that was apparent on at least two successive radiographs, but was not confirmed by MRI. The fifth patient had progressive growth plate widening and evidence of physeal cartilage hypertrophy on MRI. Subsequent off treatment radiographs showed that the growth plate changes were reversible.

Conclusion

Growth plate abnormalities occur in a small, but relevant number of patients undergoing anti‐angiogenic therapy. These results support the need for growth plate monitoring in children with open growth plates who are receiving anti‐angiogenic therapy, and for improved methods to assess toxicity of anti‐angiogenic agents to the developing skeleton. Pediatr Blood Cancer 2015;62:45–51. © 2014 Wiley Periodicals, Inc.
Second malignancies in patients with neuroblastoma: The effects of risk‐based therapy
Authors: Applebaum Mark A. , Henderson Tara O. , Lee Sang Mee , Pinto Navin , Volchenboum Samuel L. , Cohn Susan L.
Published: September 2014

Background

To investigate the incidence of second malignant neoplasms (SMN) for patients with neuroblastoma, we analyzed patients from the SEER database according to three treatment eras (Era 1: 1973–1989, Era 2: 1990–1996, and Era 3: 1997–2006) corresponding to the introduction of multi‐agent chemotherapy, risk‐based treatment, and stem cell transplant.

Procedures

The SEER database was mined for all patients with neuroblastoma or ganglioneuroblastoma. Cumulative incidence of SMN was calculated with death as a competing risk. A poisson regression model was used to estimate incidence rate ratios and 95% confidence intervals to compare the rates of SMN between patients in different Eras.

Results

The analytic cohort included 2,801 patients. Thirty‐four patients developed a SMN, accounting for 1.2% of all patients. Of the patients who developed a SMN, 47.1% received radiation for their primary neuroblastoma. Fourteen of the SMN were carcinomas, and 10 were hematologic malignancies, with six cases of acute myelogenous leukemia. There was no difference in the incidence of SMN in Era 1 compared to Era 3 (P = 0.48). The cumulative incidence of SMN at 30 years for high‐risk patients was 10.44% (95% CI 3.98–20.52%) compared to 3.57% (95% CI 1.87–6.12%) for non‐high‐risk patients (P < 0.001).

Conclusions

This study showed no increase in the incidence of SMNs for children treated in the most recent treatment era as compared to earlier Eras. However, as the risk for developing SMN does not plateau, the number of SMNs will likely continue to rise in the cohort of patients treated after 1996. Comprehensive follow‐up care for these survivors will be important. Pediatr Blood Cancer 2015;62:128–133. © 2014 Wiley Periodicals, Inc.
Structure of a partially unfolded form of Escherichia coli dihydrofolate reductase provides insight into its folding pathway
Authors: Kasper Joseph R. , Liu Pei‐Fen , Park Chiwook
Published: September 2014

Proteins frequently fold via folding intermediates that correspond to local minima on the conformational energy landscape. Probing the structure of the partially unfolded forms in equilibrium under native conditions can provide insight into the properties of folding intermediates. To elucidate the structures of folding intermediates of Escherichia coli dihydrofolate reductase (DHFR), we investigated transient partial unfolding of DHFR under native conditions. We probed the structure of a high‐energy conformation susceptible to proteolysis (cleavable form) using native‐state proteolysis. The free energy for unfolding to the cleavable form is clearly less than that for global unfolding. The dependence of the free energy on urea concentration (m‐value) also confirmed that the cleavable form is a partially unfolded form. By assessing the effect of mutations on the stability of the partially unfolded form, we found that native contacts in a hydrophobic cluster formed by the F‐G and Met‐20 loops on one face of the central β‐sheet are mostly lost in the partially unfolded form. Also, the folded region of the partially unfolded form is likely to have some degree of structural heterogeneity. The structure of the partially unfolded form is fully consistent with spectroscopic properties of the near‐native kinetic intermediate observed in previous folding studies of DHFR. The findings suggest that the last step of the folding of DHFR involves organization in the structure of two large loops, the F‐G and Met‐20 loops, which is coupled with compaction of the rest of the protein.
Effects of active site cleft residues on oligosaccharide binding, hydrolysis, and glycosynthase activities of rice BGlu1 and its mutants
Authors: Pengthaisong Salila , Ketudat Cairns James R.
Published: September 2014

Rice BGlu1 (Os3BGlu7) is a glycoside hydrolase family 1 β‐glucosidase that hydrolyzes cellooligosaccharides with increasing efficiency as the degree of polymerization (DP) increases from 2 to 6, indicating six subsites for glucosyl residue binding. Five subsites have been identified in X‐ray crystal structures of cellooligosaccharide complexes with its E176Q acid‐base and E386G nucleophile mutants. X‐ray crystal structures indicate that cellotetraose binds in a similar mode in BGlu1 E176Q and E386G, but in a different mode in the BGlu1 E386G/Y341A variant, in which glucosyl residue 4 (Glc4) interacts with Q187 instead of the eliminated phenolic group of Y341. Here, we found that the Q187A mutation has little effect on BGlu1 cellooligosaccharide hydrolysis activity or oligosaccharide binding in BGlu1 E176Q, and only slight effects on BGlu1 E386G glycosynthase activity. X‐ray crystal structures showed that cellotetraose binds in a different position in BGlu1 E176Q/Y341A, in which it interacts directly with R178 and W337, and the Q187A mutation had little effect on cellotetraose binding. Mutations of R178 and W337 to A had significant and nonadditive effects on oligosaccharide hydrolysis by BGlu1, pNPGlc cleavage and cellooligosaccharide inhibition of BGlu1 E176Q and BGlu1 E386G glycosynthase activity. Hydrolysis activity was partially rescued by Y341 for longer substrates, suggesting stacking of Glc4 on Y341 stabilizes binding of cellooligosaccharides in the optimal position for hydrolysis. This analysis indicates that complex interactions between active site cleft residues modulate substrate binding and hydrolysis.