bluuebunny/crossref_metadata_2025_split huggingface dataset:
Animal Models of Idiosyncratic, Drug‐Induced Liver Injury: Emphasis on the Inflammatory Stress Hypothesis
Authors: Zou Wei , Roth Robert A. , Ganey Patricia E. 
Published: February 2012

AbstractIdiosyncratic, drug‐induced liver injury (IDILI) can result in permanent disability or death in patients, thus these reactions have obvious importance to human health. In addition, these reactions lead to withdrawals and restrictions in the use of efficacious drugs. Mechanisms by which IDILI occurs are unknown, and although many hypotheses have been proposed, there exists no conclusive support in people for any of them. Drugs that cause IDILI typically escape identification until they are in use in large numbers of people; accordingly, animal models to identify early in development which drugs have the propensity to cause IDILI and to study potential mechanisms would be useful. The inflammatory stress hypothesis proposes that an inflammatory episode can interact with drug exposure to render an individual susceptible to IDILI. This hypothesis has been the basis for the development of animal models in which rodents develop liver injury from exposure to drugs that cause IDILI in people. This chapter describes current hypotheses regarding IDILI and elaborates on the inflammatory stress hypothesis. Results of studies using the drug sulindac are emphasized.
Regulation of Drug Metabolizing Enzymes and Transporters in Infection, Inflammation, and Cancer
Authors: Morgan Edward T. , Lee Choon‐Myung , Nyagode Beatrice A. 
Published: February 2012

AbstractUnder conditions of innate immune system activation (i.e., inflammation), the functions of specific cytochrome P450 enzymes, other drug metabolizing enzymes (DMEs), and drug transporters (DTs) are altered in the liver, small intestine, lung, kidney, and central nervous system (CNS). Many of these effects are primarily manifest at the transcriptional/RNA level, leading to corresponding changes in protein levels and function. This not only leads to altered drug and xenobiotic toxicity and action in diseased humans, but also has importance for disease therapy with biologic drugs that target inflammatory mediators or their receptors. Major roles for proinflammatory cytokines such as interleukin‐6 (IL‐6), IL‐1β, and tumor necrosis factor‐α(TNFα) are inferred from the abilities of these agents to affect DMEs and DTs in cultured cells andin vivo, but thein vivocontributions of cytokines to regulation of these proteins in different inflammatory disease states is still poorly understood.
Infusion Nanoelectrospray Ionization Mass Spectrometry
Authors: Henion Jack 
Published: February 2012

AbstractThis report reviews the introductory aspects of electrospray ionization coupled with mass spectrometry and highlights those aspects of electrospray that play an important role in its application to analyzing real‐world samples. Following a discussion of matrix effects, factors that affect analyte response and sensitivity, and the flow rate factors of the spray solvent, the relative benefits of on‐line HPLC or UPLC are contrasted with an infusion electrospray sample introduction approach, which, of course, precludes any aspects of chromatographic separation. The introduction of samples via infusion bypasses the need for a chromatographic system, including its pumps, autosampler, separation column, and the compromise of a mobile phase, which must accomplish the chromatographic separation while also allowing the electrospray ionization process to occur. Thus, infusion sample introduction is in principle much easier to accomplish. However, there are clear benefits to employing HPLC for the analysis of complex samples. So, how can infusion sample introduction be worthwhile?It can be worthwhile because nanoelectrospray, or electrospray at 20–500 nL/min solvent flow rates, provides some unique benefits over the higher flow rate regime that has been customarily used. Thus, nanoelectrospray provides improved sensitivity, reduced matrix suppression, and normalized response from differing analytes and conserves precious samples if this is an issue. This review overviews these principles and provides several successful examples of published work where infusion nanoelectrospray experiments have merit.
Whole‐Body Autoradiography and Microautoradiography in Drug Discovery and Development
Authors: Solon Eric G. 
Published: February 2012

AbstractThis chapter describes the following three approaches used to study the tissue distribution of chemical and biological compounds in laboratory animals: (i) organ collection, homogenization/combustion, and liquid scintillation counting (LSC) analysis; (ii) whole‐body autoradiography (WBA), which includes quantitative whole‐body autoradiography (QWBA); and (iii) microautoradiography (MARG), which qualitatively resolves the localization of compounds to the cellular level in a histological preparation. LSC, WBA, QWBA, and MARG studies require the use of a radiolabeled chemical or biological test compound, which provides for the tracking and quantification of both the parent molecule and potential metabolites that might be formed. This chapter discusses the history, advantages, limitations, and examples of the application of each technique.
CYP450 Enzymes in Drug Discovery and Development: An Overview
Authors: Xu Lin , Das Biplab , Prakash Chandra 
Published: February 2012

AbstractCytochrome P450 enzymes play an important role in the metabolism of foreign molecules (drugs and environmental chemicals) and endogenous compounds. This large enzyme family facilitates to eliminate xenobiotics from the body and catalyzes the catabolism of endogenous compounds for their physiological functions. In this chapter, we describe the most recent advances in our knowledge and application of P450 enzymes in drug discovery and development with particular emphasis on their involvement in the metabolism of drugs. In addition, we have also summarized the basic catalytic activity of this enzyme family, commonly observed biotransformation in drugs, the species and ethnic variation in the expression of P450 enzymes, and the tools used to extrapolate metabolism and toxicity in animals to humans.
Predicting Human Biotransformation Pathways
Authors: Anderson Shelby , Luffer‐Atlas Debra , Pat Knadler Mary 
Published: February 2012

AbstractKnowledge of the human biotransformation pathways is critical for safe and effective dosing of a new molecular entity (NME). Predicting human biotransformation pathways begins in the early discovery phase wherein silicoandin vitrotools are utilized. As development progresses, additional studies are conducted bothin vitroandin vivo, first in animals and then in humans.In vivostudies start with determination of a metabolic profile followed by administration of a radiolabeled dose of an NME to determine the extent of metabolism and the identity of the metabolites.
Laboratory Maintenance of Agrobacterium
Authors: Morton Elise R. , Fuqua Clay 
Published: February 2012

AbstractAgrobacterium species are plant‐associated relatives of the rhizobia. Several species cause plant diseases such as crown gall and hairy root, although there are also avirulent species. A. tumefaciens is the most intensively studied species and causes crown gall, a neoplastic disease that occurs on a variety of plants. Virulence is specified by large plasmids, and in the case of A. tumefaciens this is called the Ti (tumor‐inducing) plasmid. During pathogenesis, virulent agrobacteria copy a segment of the Ti plasmid and transfer it to the plant, where it subsequently integrates into the plant genome and expresses genes that result in the disease symptoms. A. tumefaciens has been used extensively as a plant genetic engineering tool, and is also a model microorganism that has been well studied for host‐microbe associations, horizontal gene transfer, cell‐cell communication, and biofilm formation. This unit describes standard protocols for laboratory cultivation of A. tumefaciens. Curr. Protoc. Microbiol. 24:3D.1.1‐3D.1.16. © 2012 by John Wiley & Sons, Inc.
Laboratory Maintenance of Helicobacter Species
Authors: Blanchard Thomas G. , Nedrud John G. 
Published: February 2012

AbstractHelicobacter species are Gram‐negative bacteria that colonize the gastric or intestinal mucosa of many mammalian and avian hosts and induce histologic inflammation. The association of H. pylori with gastritis, peptic ulcer disease, and gastric cancers makes it a significant human pathogen. Animal models for these diseases are being used to explore the pathogenesis of H. pylori infection and in vaccine development. Both bacterial and host factors contribute to Helicobacter pathogenesis; therefore, the microbiology is very important. This unit describes how to culture the most commonly used gastric Helicobacter species, H. pylori, H. mustelae, and H. felis. Curr. Protoc. Microbiol. 24:8B.1.1‐8B.1.19. © 2012 by John Wiley & Sons, Inc.
Cell Culture Assay for Transient Replication of Human and Animal Papillomaviruses
Authors: Wilson Van G. 
Published: February 2012

AbstractThis unit contains protocols for evaluation of replication functionality of papillomavirus genomes or subgenomic fragments. Replication is measured after transient cotransfection of the genome (or subgenomic fragment) with expression vectors encoding the viral E1 and E2 proteins. Input DNA is methylated at the adenine of GATC sequences by propagation in E. coli. DNA that replicates in mammalian cells will lose the adenine methylation and become DpnI‐resistant, while residual methylated input DNA will remain DpnI‐sensitive. After transfection, DNA extraction, and DpnI digestion, replicated DNA can be detected by Southern blotting as a full‐length plasmid, since it is resistant to digestion. This assay can be used to map the genomic location of a functional origin or to evaluate replication activity of mutations in either the origin DNA sequences or the E1 or E2 proteins. Curr. Protoc. Microbiol. 24:14B.1.1‐14B.1.18. © 2012 by John Wiley & Sons, Inc.
Human Cytomegalovirus: Bacterial Artificial Chromosome (BAC) Cloning and Genetic Manipulation
Authors: Paredes Anne M. , Yu Dong 
Published: February 2012

AbstractThe understanding of human cytomegalovirus (HCMV) biology was long hindered by the inability to perform efficient viral genetic analysis. This hurdle was recently overcome when the genomes of multiple HCMV strains were cloned as infectious bacterial artificial chromosomes (BACs). The BAC system takes advantage of the single‐copy F plasmid of E. coli that can stably carry large pieces of foreign DNA. In this system, a recombinant HCMV virus carrying a modified F plasmid is first generated in eukaryotic cells. Recombinant viral genomes are then isolated and recovered in E. coli as BAC clones. BAC‐captured viral genomes can be manipulated using prokaryotic genetics, and recombinant virus can be reconstituted from BAC transfection in eukaryotic cells. The BAC reverse genetic system provides a reliable and efficient method to introduce genetic alterations into the viral genome in E.coli and subsequently analyze their effects on virus biology in eukaryotic cells. Curr. Protoc. Microbiol. 24:14E.1.1‐14E.1.33. © 2012 by John Wiley & Sons, Inc.
Tin Oxide with Controlled Morphology and Crystallinity by Atomic Layer Deposition onto Graphene Nanosheets for Enhanced Lithium Storage
Authors: Li Xifei , Meng Xiangbo , Liu Jian , Geng Dongsheng , Zhang Yong , Banis Mohammad Norouzi , Li Yongliang , Yang Jinli , Li Ruying , Sun Xueliang , Cai Mei , Verbrugge Mark W. 
Published: February 2012

AbstractAs one of the most promising negative electrode materials in lithium‐ion batteries (LIBs), SnO2 experiences intense investigation due to its high specific capacity and energy density, relative to conventional graphite anodes. In this study, for the first time, atomic layer deposition (ALD) is used to deposit SnO2, containing both amorphous and crystalline phases, onto graphene nanosheets (GNS) as anodes for LIBs. The resultant SnO2‐graphene nanocomposites exhibit a sandwich structure, and, when cycled against a lithium counter electrode, demonstrate a promising electrochemical performance. It is demonstrated that the introduction of GNS into the nanocomposites is beneficial for the anodes by increasing their electrical conductivity and releasing strain energy: thus, the nanocomposite electrode materials maintain a high electrical conductivity and flexibility. It is found that the amorphous SnO2‐GNS is more effective than the crystalline SnO2‐GNS in overcoming electrochemical and mechanical degradation; this observation is consistent with the intrinsically isotropic nature of the amorphous SnO2, which can mitigate the large volume changes associated with charge/discharge processes. It is observed that after 150 charge/discharge cycles, 793 mA h g−1 is achieved. Moreover, a higher coulombic efficiency is obtained for the amorphous SnO2‐GNS composite anode. This study provides an approach to fabricate novel anode materials and clarifies the influence of SnO2 phases on the electrochemical performance of LIBs.
WDR62 missense mutation in a consanguineous family with primary microcephaly
Authors: Bacino Carlos A. , Arriola Luis A. , Wiszniewska Joanna , Bonnen Penelope E. 
Published: February 2012

AbstractWe report on a consanguineous couple with two affected sons who presented with primary microcephaly and moderate to severe intellectual disabilities. A SNP array uncovered two overlapping regions of copy‐neutral absence of heterozygosity (AOH) in both sibs. This led to sequencing of WDR62, a gene that codes for a spindle pole protein recently identified as a cause of primary microcephaly. A homozygous missense mutation in WDR62, p.E400K, was found in both boys and segregated with the condition in this family. WDR62 is one of seven genes responsible for autosomal recessive primary microcephaly (MCPH), and appears to be one of the most frequently involved in MCPH following ASPM. Studies of ASPM and WDR62 should perhaps be pursued in all cases of primary microcephaly with or without gross brain malformations. © 2012 Wiley Periodicals, Inc.
Familial 16q24.3 microdeletion involving ANKRD11 causes a KBG‐like syndrome
Authors: Sacharow Stephanie , Li Deling , Fan Yao Shan , Tekin Mustafa 
Published: February 2012

AbstractHaploinsufficiency of ANKRD11 encoding ankyrin repeat domain‐containing protein 11 was recently reported as the cause of a syndrome due to microdeletion, characterized by intellectual disability with minor facial anomalies and short stature. Most recently, intragenic mutations of ANKRD11 were found in a cohort of patients with KBG syndrome. KBG is an autosomal dominant intellectual disability syndrome characterized by short stature, characteristic facial appearance, macrodontia, and skeletal anomalies. It remains unknown if deletion of the entire ANKRD11 causes KBG syndrome. We present a mother and child with a heterozygous 365 Kb deletion at 16q24.3 containing ANKRD11, ZNF778, and SPG7 genes. The child presented with developmental delay, facial anomalies, hand anomalies, and a congenital heart defect. The mother has short stature, facial anomalies, macrodontia, hand anomalies, and learning disability. Both individuals had many findings reported in KBG syndrome and the family met the suggested diagnostic criteria. However, typical macrodontia with fused incisors, costovertebral anomalies, and delayed bone age were not present. We conclude that microdeletions involving ANKRD11 result in a phenotype similar to that of KBG syndrome. © 2012 Wiley Periodicals, Inc.
The ever‐expanding spectrum of congenital muscular dystrophies
Authors: Mercuri Eugenio , Muntoni Francesco 
Published: February 2012

AbstractCongenital muscular dystrophies are a highly heterogeneous group of conditions. In the last few years the identification of several new genes encoding for both glycosyltransferases and structural proteins has expanded the spectrum of the known forms. New classifications based on combined clinical, genetic and pathological data include all the recently discovered genes and allow an easier identification of the different forms and insight on pathogenetic mechanisms. The aim of this review is to discuss the most recent advances in this field, providing a conceptual framework to help the understanding of the responsible mechanisms and, when available, an update on the therapeutic perspectives.ANN NEUROL 2012;72:9–17
Nonisothermal cure kinetics and diffusion effect of liquid‐crystalline epoxy sulfonyl bis(1,4‐phenylene)bis[4‐(2,3‐epoxypropyloxy)benzoate] resin with aromatic diamine
Authors: Gao Jungang , Huo Li , Du Yonggang 
Published: February 2012

AbstractThe curing kinetics of the liquid‐crystalline epoxy resin sulfonyl bis(1,4‐phenylene)bis[4‐(2,3‐epoxypropyloxy)benzoate] with 4,4′‐diaminodiphenylsulfone was investigated by nonisothermal differential scanning calorimetry. The relationship between the apparent activation energy (Ea) and the conversion was determined, and the effects of the molecular structure and the order of liquid crystallinity on Ea are discussed in detail. Some parameters were evaluated with the autocatalytic kinetic model of the Šesták–Berggren (S–B) equation. The results show that there were some deviations of these simulation curves from the experimental curves at high heating rates and in the late stage of the curing reaction. The diffusion effect in the nonisothermal curing reaction is discussed, and a diffusion factor was proposed and introduced into the S–B equation. Then, a modified S–B equation was created, as follows:
${{d\alpha } \over {dt}} = K\alpha ^m (1 - \alpha )^n \times {1 \over {1 + \exp \left[ {C\left( {\alpha - \alpha _c } \right)} \right]}}$, where α is the conversion, t is the time, m and n are reaction orders, K is rate constant, C is the diffusion coefficient, and αc is the critical conversion. The theoretical simulation curves agreed very well with the experimental data as determined with the modified S–B equation, which may be more useful for describing and predicting the nonisothermal curing reaction kinetics of epoxy resin. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Effect of oxidation progress of tributylborane on the grafting of polyolefins
Authors: Liu Shujuan , Zheng Zhen , Li Minrui , Wang Xinling 
Published: February 2012

AbstractEffect of the oxidation progress of tributylborane on the grafting reaction of PMMA onto high‐density polyethylene (HDPE) and isotropic polypropylene (iPP) surface with tributylborane as initiator was studied in detail. The oxidation of tributylborane was triggered by the slow diffused oxygen or exposed contact to oxygen, so that the oxidation progress of tributylborane would be different. The grafted polyolefin surfaces were characterized by attenuated total reflection infrared (ATR‐IR) spectroscopy, X‐ray photoelectron spectroscopic (XPS), scanning electron microscope (SEM) and so on. The results of ATR‐IR spectroscopy and XPS analysis suggested that PMMA could be grafted onto polyolefin surfaces successfully through these two ways, but the grafting degrees were varied due to the different oxidation progresses of tributylborane. The surface morphologies of the polyolefin indicated the different grafting degrees as a result of different oxidation progress of tributylborane. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Vegetable oil‐based highly branched polyester modified epoxy based low VOC high solid industrial paint
Authors: Konwar Uday , Karak Niranjan , Jana Tirthankar 
Published: February 2012

AbstractMesua ferrea L. seed oil based highly branched polyester modified epoxy resin has been utilized as a binder system for a low volatile organic compound (VOC) containing high solid paint formulation. The highly branched low molecular weight polyester resin acts as the reactive diluent of the epoxy resin which satisfies to reduce VOC emission and produces high solid paint system. The prepared Mesua ferrea L. seed oil based highly branched polyester modified epoxy paint (test paint) was assessed against commercially available epoxy paint (standard paint) for protective coating application. Different physical and performance properties of the paint viz. nonvolatile content, specific gravity, viscosity, drying time, scratch hardness, gloss, impact resistance, and chemical properties such as corrosion resistance, salt spray resistance, UV resistance were measured as per the standard methods. The surface morphology and the thermal stability of the paints were also studied by scanning electron microscope (SEM) and thermogravimetric analysis (TGA). The shear thinning behavior was observed for both the paints as indicated by rheological study. The results indicate that the test paint is comparable with the standard paint. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Preparation of highly exfoliated and transparent polycarbonate/clay nanocomposites by melt blending of polycarbonate and poly(methyl methacrylate)/clay nanocomposites
Authors: Dhibar Saptarshi , Kar Prativa , Khatua B. B. 
Published: February 2012

AbstractIn this report, we introduce an industrially feasible method that involves melt blending of polycarbonate (PC) and in situ suspension polymerized exfoliated PMMA/clay (Na+MMT) nanocomposites to prepare highly exfoliated PC/clay nanocomposites. The rational behind this is that PC is well known to form miscible blend with low molecular weight PMMA. Thus, low molecular weight PMMA/clay exfoliated nanocomposites were prepared by suspension polymerization using pre‐exfoliated clay (Na+MMT) in water media during the polymerization. The (80/20 w/w) PC/PMMA blends without and with Na+MMT showed single glass transition temperature (Tg), indicating complete miscibility of the polymers in the blend. The surface morphologies of the composites were studied by scanning electron microscopy (SEM). Wide‐angle X‐ray diffraction and transmission electron microscope (TEM) studies of the nanocomposites revealed delamination of the clay silicate layers in the PC matrix. The properties of the (80/20 w/w) PC/PMMA‐Na+MMT nanocomposites were significantly higher than that of the pure PC. Moreover, retention of the optical transparency of PC in the nanocomposites could be due to the presence of unmodified clay (Na+MMT), which did not contain any organic modifier (quaternary ammonium salt) that could decompose during melt mixing of PC at high temperature (≈ 280°C). © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012