bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of soft segment content and linker length on shape recovery and mechanical properties of laterally linked polyurethane copolymer
Authors: Chung Yong‐Chan , Khiem Nguyen Duy , Won Choi Jae , Chul Chun Byoung 
Published: December 2010

AbstractLateral flexible linking of shape memory polyurethane (SMPU) by a polyethyleneglycol (PEG) linker through the allophanate linking method was studied, while adjusting the soft segment content and PEG length. The SMPU was composed of 4,4′‐methylenebis(phenylisocyanate) (MDI), poly(tetramethyleneglycol) (PTMG), 1,4‐butanediol (BD), and PEG‐200 as a linker. A second MDI was used to connect the carbamate group of the SMPU chain and PEG. The impact of soft segment content and PEG length on the mechanical properties and shape recovery of two series of SMPU were compared. In the best case, a 545% increase in maximum stress compared to a linear polymer was attained. The flexibly crosslinked SMPUs behave similarly to natural rubber in their stress–strain curve, but their tensile mechanical properties surpassed those of natural rubber. Shape recovery went up to 96%, which is among the best SMPUs tested so far, and shape recovery remained above 90% after four cyclic tests. The extraordinary shape memory results are analyzed and discussed together with DSC and IR data. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Face processing abilities in relatives of individuals with ASD
Authors: Wallace Simon , Sebastian Catherine , Pellicano Elizabeth , Parr Jeremy , Bailey Anthony 
Published: December 2010

AbstractIndividuals with an autism spectrum disorder (ASD) show difficulties identifying familiar faces, recognizing emotional expressions and judging eye‐gaze direction. Recent research suggests that relatives of individuals with AS also show impairments in some aspects of face processing but no study has comprehensively assessed the nature and extent of face‐processing difficulties in a group of relatives. This study compared the performance of 22 parents/adult siblings of individuals with ASD (“relatives” group), 26 adults with ASD, and 26 typically developing adults on tasks of face discrimination, facial expression recognition and judging eye‐gaze direction. Relatives of individuals with ASD were less able to discriminate subtle differences between faces than typically developing adults, but were more sensitive to such differences than adults with ASD. Furthermore, relatives were significantly worse at identifying expressions of fear and disgust than typically developing adults and failed to show the typical sensitivity to direct compared with averted eye‐gaze direction—a strikingly similar pattern to that observed in adults with ASD. These findings show that atypical patterns of face processing are found in some relatives of individuals with ASD and suggest that these difficulties may represent a cognitive endophenotype.
Application of high‐resolution melting for genotyping bovine mitochondrial DNA
Authors: Zhou Zai‐Wei , Yan Jing‐Bin , Li Hua , Ren Zhao‐Rui 
Published: December 2010

AbstractRecent studies have demonstrated that mitochondrial DNA (mtDNA) haplotype has a significant impact on the efficiency of bovine somatic cell nuclear transfer. Conventional methods for detecting mtDNA variations and haplotypes, such as restriction fragment length polymorphism (RFLP), temporal temperature gradient gel electrophoresis, dHPLC and sequencing, are labor intensive or expensive and have low sensitivity. High‐resolution melting (HRM) analysis is a new technique for mutation detection and has the advantages of speed, cost, and accuracy. Here, we describe the genotyping of bovine mtDNA using HRM analysis. DNA samples containing mtDNA were extracted from 75 Holstein cows and subjected to rapid‐cycle (<20 min) PCR of small amplicons (<120 bp) using specific primer sets. Capillaries containing the PCR products were then subjected to HRM analysis; data were acquired in 2 min and analyzed using the instrument's software. Five common bovine mtDNA single nucleotide polymorphisms were identified: 9602 G>A, 169 A>G, 166A>G with 173A>G, and 363C>G. These results agree with both sequencing and RFLP analysis. In addition, a very small amount of heteroplasmic variants (<5%) was sufficiently to be distinguished by HRM analysis that would be very useful to differentiate heteroplasmy vs. homoplasmy. HRM analysis thus provides a new approach to genotyping bovine mtDNA sequence variations and has many advantages over other methods, including speed of analysis, cost, and accuracy. We believe this will be a valuable technique for determining the efficiency of nuclear transfer in cloned embryos and for studying maternal effects on nuclear‐cytoplasm interactions. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Determination of yeast viability during a stress‐model alcoholic fermentation using reagent‐free microscopy image analysis
Authors: Tibayrenc Pierre , Ghommidh Charles , Preziosi‐Belloy Laurence 
Published: December 2010

AbstractA dedicated microscopy imaging system including automated positioning, focusing, image acquisition, and image analysis was developed to characterize a yeast population with regard to cell morphology. This method was used to monitor a stress‐model alcoholic fermentation with Saccharomyces cerevisiae. Combination of dark field and epifluorescence microscopy after propidium iodide staining for membrane integrity showed that cell death went along with important changes in cell morphology, with a cell shrinking, the onset of inhomogeneities in the cytoplasm, and a detachment of the plasma membrane from the cell wall. These modifications were significant enough to enable a trained human operator to make the difference between dead and viable cells. Accordingly, a multivariate data analysis using an artificial neural network was achieved to build a predictive model to infer viability at single‐cell level automatically from microscopy images without any staining. Applying this method to in situ microscope images could help to detect abnormal situations during a fermentation course and to prevent cell death by applying adapted corrective actions. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Expression and purification of cGMP grade NY‐ESO‐1 for clinical trials
Authors: Lowe Adam J. , Bardliving Cameron L. , Huang Chung‐Jr , Teixeira Leonardo M. , Damasceno Leonardo M. , Anderson Kyle A. , Ritter Gerd , Old Lloyd J. , Batt Carl A. 
Published: December 2010

AbstractNY‐ESO‐1 is a cancer testis antigen expressed in numerous cancers. Initial tests have shown its efficacy as a cancer vaccine, stimulating the body's own immune response against the invading tumor. To produce enough material for phase I clinical trials, a process using current good manufacturing practices to produce clinical grade material was developed and executed. His‐tagged NY‐ESO‐1 was expressed in C41DE3 Escherichia coli under control of the T‐7 promoter. NY‐ESO‐1 was produced in a 20 L fed‐batch fermentation utilizing a pH‐stat control scheme. The protein was then purified from inclusion bodies using a three‐column process that achieved a yield of over 3.4 g and endotoxin below the detection limit of 0.005 EU/μg protein. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Enzymatic hydrolysis of chemithermomechanically pretreated sugarcane bagasse and samples with reduced initial lignin content
Authors: Mendes Fernanda M. , Siqueira Germano , Carvalho Walter , Ferraz André , Milagres Adriane M. F. 
Published: December 2010

AbstractChemithermomechanical (CTM) processing was used to pretreat sugarcane bagasse with the aim of increasing cell wall accessibility to hydrolytic enzymes. Yields of the pretreated samples were in the range of 75–94%. Disk refining and alkaline‐CTM and alkaline/sulfite‐CTM pretreatments yielded pretreated materials with 21.7, 17.8, and 15.3% of lignin, respectively. Hemicellulose content was also decreased to some extent. Fibers of the pretreated materials presented some external fibrillation, fiber curling, increased swelling, and high water retention capacity. Cellulose conversion of the alkaline‐CTM‐ and alkaline/sulfite‐CTM‐pretreated samples reached 50 and 85%, respectively, after 96 h of enzymatic hydrolysis. Two samples with low initial lignin content were also evaluated after the mildest alkaline‐CTM pretreatment. One sample was a partially delignified mill‐processed bagasse. The other was a sugarcane hybrid selected in a breeding program. Samples with lower initial lignin content were hydrolyzed considerably faster in the first 24 h of enzymatic digestion. For example, enzymatic hydrolysis of the sample with the lowest initial lignin content (14.2%) reached 64% cellulose conversion after only 24 h of hydrolysis when compared with the 30% observed for the mill‐processed bagasse containing an initial lignin content of 24.4%. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Probing the active site of cellodextrin phosphorylase from Clostridium stercorarium: Kinetic characterization, ligand docking, and site‐directed mutagenesis
Authors: Hai Tran Giang , Desmet Tom , De Groeve Manu R. M. , Soetaert Wim 
Published: December 2010

AbstractCellodextrin phosphorylase from Clostridium stercorarium has been recombinantly expressed in Escherichia coli for the first time. Kinetic characterization of the purified enzyme has revealed that aryl and alkyl β‐glucosides can be efficiently glycosylated, an activity that has not yet been described for this enzyme class. To obtain a better understanding of the factors that determine the enzyme's specificity, homology modeling and ligand docking were applied. Residue W168 has been found to form a hydrophobic stacking interaction with the substrate in subsite +2, and its importance has been examined by means of site‐directed mutagenesis. The mutant W168A retains about half of its catalytic activity, indicating that other residues also contribute to the binding affinity of subsite +2. Finally, residue D474 has been identified as the catalytic acid, interacting with the glycosidic oxygen between subsites −1 and +1. Mutating this residue results in complete loss of activity. These results, for the first time, provide an insight in the enzyme–substrate interactions that determine the activity and specificity of cellodextrin phosphorylases. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Three‐Component Reactions of Isochromenylium Tetrafluoroborates via Non‐Classical [4+2]‐Intermediates: Mild One‐Step Metal‐Free Synthesis of Functionalized Dihydronaphthalenes and Tetrahydronaphthalenes
Authors: Hu Zhi‐Long , Yang Zhen‐Yu , Wang Shaozhong , Yao Zhu‐Jun 
Published: December 2010

AbstractTwo novel types of elegant three‐component reactions of stable isochromenylium tetrafluoroborates (ICTBs) have been developed under mild metal‐free conditions in this work. Mechanistically, these reactions are commonly initiated by a [4+2]‐cycloaddition between the non‐classical isochromenylium diene and the aldehyde–enol, and terminated by the following addition of weak nucleophiles, including nitriles or the second equivalent of aldehydes, in a one‐pot fashion. The developed methodologies exhibit excellent chemoselectivity, regioselectivity, and diastereoselectivity, and provide a new convenient access to functionalized dihydronaphthalenes and tetrahydronaphthalenes.
Structure–Activity Relationship Refinement and Further Assessment of Indole‐3‐glyoxylamides as a Lead Series against Prion Disease
Authors: Thompson Mark J. , Louth Jennifer C. , Ferrara Steven , Sorrell Fiona J. , Irving Benjamin J. , Cochrane Edward J. , Meijer Anthony J. H. M. , Chen Beining 
Published: December 2010

AbstractStructure–activity relationships within the indole‐3‐glyoxylamide series of antiprion agents have been explored further, resulting in discovery of several new compounds demonstrating excellent activity in a cell line model of prion disease (EC50 <10 nM). After examining a range of substituents at the para‐position of the N‐phenylglyoxylamide moiety, five‐membered heterocycles containing at least two heteroatoms were found to be optimal for the antiprion effect. A number of modifications were made to probe the importance of the glyoxylamide substructure, although none were well tolerated. The most potent compounds did, however, prove largely stable towards microsomal metabolism, and the most active library member cured scrapie‐infected cells indefinitely on administration of a single treatment. The present results thereby confirm the indole‐3‐glyoxylamides as a promising lead series for continuing in vitro and in vivo evaluation against prion disease.
Impact of DNA patents on pharmacogenomics research and development: economic and policy issues
Authors: Paci Daniele , Hopkins Michael M. , Zika Eleni , Ibarreta Dolores 
Published: December 2010

AbstractThe science of pharmacogenetics and pharmacogenomics (or collectively PGx) has advanced rapidly in recent years, and some technologies based on these developments have entered into use. It is notable that these advances have occurred in parallel with related advances in genetic testing, led by developments in testing services for the diagnosis of rare disorders that share Mendelian patterns of inheritance. However, a profusion of patents on nucleotide sequences (often termed “gene patents”) has led to widespread concern that disputes over intellectual property could hamper the development and diffusion of these technologies. This article outlines the recent evidence from major empirical studies on the complex landscape of diagnostic DNA patents in the United States and Europe and discusses the traditional arguments in favor and against gene patenting in PGx and genetic testing. It also explores the extent to which concerns in clinical genetics might be relevant to PGx. We find that although recent evidence on genetic testing suggests that many of the issues might have been overestimated or overemphasized, no dedicated studies have been published on the intellectual property aspects of PGx. Drug Dev Res 71: 485–491, 2010. © 2010 Wiley‐Liss, Inc.
The increasing role of health economic evaluations in drug development
Authors: Annemans Lieven , Cleemput Irina , Simoens Steven , Arickx Francis , Hulstaert Frank , Bogaert Marc 
Published: December 2010

AbstractThe goal of health care policies is to maximize the health of the population within the limits of the available budget and taking into account equity considerations. For innovative drugs, this means that an increasing number are being assessed in terms of their value for money, which is the amount of additional health that can be achieved per additional euro, pound, dollar, or other currency invested. Ideally such assessments and resulting appraisals and decisions should be made in a transparent and efficient way. Transparent means consisting of clear procedures and criteria such as relative effectiveness, cost effectiveness, budget impact, social, and ethical consequences. Transparent also means that stakeholders (physicians, patients, industry, and others) are involved in the assessment and decision‐making process. Efficient means that, on a European level, duplication of efforts is avoided by aligning the processes for market authorization and those for the assessment of value for money. Drug Dev Res 71: 457–462, 2010. © 2010 Wiley‐Liss, Inc.
Pharmaceutical market access and the challenges of health technology assessment in the United Kingdom
Authors: Tolley Keith 
Published: December 2010

AbstractHealth Technology Assessment (HTA) has been formally used in the United Kingdom for more than 10 years to help determine evidence‐based decisions on the access to new drugs, based on evidence of clinical and cost‐effectiveness. Separate HTA systems have developed in England and Wales (NICE, AWMSG), and Scotland (SMC). The primary clinical evidence desired for technology appraisal by the HTA bodies is the comparative randomized controlled trial because of its good internal validity, but the role and value of observational study designs for providing data on real‐world effectiveness have been recognized in the methods guidance of these bodies. To date HTA has had a fairly limited impact on drug development and clinical trial design in the United Kingdom, coupled with limited use to date of non‐RCT data for assessing treatment effect and outcomes in NICE/SMC appraisals. Nonetheless, with new initiatives such as closer regulatory and HTA coordination in Europe, and “conditional market access” schemes such as the Innovation Pass in the United Kingdom, in the future pharmaceutical companies are likely to need to adopt a more flexible approach to drug development and clinical data collection involving RCT, observational data collection, and indirect comparisons to meet the needs to provide relevant clinical and cost‐effectiveness evidence at drug launch and post launch. Drug Dev Res 71: 478–484, 2010. © 2010 Wiley‐Liss, Inc.
Economic evaluations of pharmacogenetic and genomic screening programs: update of the literature
Authors: Vegter Stefan , Jansen Esther , Postma Maarten J. , Boersma Cornelis 
Published: December 2010

AbstractPharmacogenetics and pharmacogenomics show great potential for developing individual treatment modalities to achieve optimal therapy effectiveness. Economic analyses are performed to determine whether pharmacogenetic screening strategies provide good value for money. The current review provides an update of published economic studies. Economic analyses of pharmacogenetic screening programs published between 2000 and July 2010 were included in the review. Information was extracted on research area, genetic information, type of economic analysis, key aspects of adherence to economic guidelines, costs and commercial availability of genetic tests, and the role of the funding party. A total of 42 economic studies on pharmacogenetic screening strategies were included. Over time, more cost‐utility analyses were performed, longer time windows were employed, and more extensive sensitivity analyses were conducted. Considerable differences in costs of screening tests for the same polymorphism were found, which often, but not always, had a large influence on the costs of screening strategies. Most studies were conducted from an academic or hospital perspective without direct links to pharmaceutical or diagnostic manufacturers. The quality of economic analyses of pharmacogenetic screening programs has improved over time. However, input variables are not always clearly described. In particular, substantial variation exists in the reported costs of the pharmacogenetic tests. Often these test costs are considered a major cost driver and could therefore be of particular importance for the interpretation of cost‐effectiveness results. Furthermore, the economic studies seem to be conducted to increase awareness of possibilities and perspectives of genetic testing rather than to influence policy decisions on reimbursement. Drug Dev Res 71: 492–501, 2010.  © 2010 Wiley‐Liss, Inc.
Implementation of innovative pharmacogenetic tests into practice in Taiwan: an institutional perspective
Authors: Chen Hsiang‐Yin , Chen Li‐Chia 
Published: December 2010

AbstractPharmacogenetic tests are proposed as a means of targeting therapy to patients such that ineffective medicine prescription and adverse events are reduced and overall benefit in terms of improved health outcomes is maximized. However, the true impact of introducing pharmacogenetic tests into clinical practice remains to be confirmed. This commentary presents some of the key requirements in developing a pharmacogenetic clinical practice model in a hospital setting. The analysis considers the need to select carefully which pharmacogenetic tests are best offered, while balancing the cost to the institution given the potential benefits to the patient population base. Drawing on our experience in Taiwan, we recommend that developing a hospital task force for pharmacogenetic testing is a recommended approach to: (1) set quality standards on how best to conduct the test, (2) provide a pro forma for interpreting results, (3) prescribe treatment appropriately according to results, and (4) design an educational program for all relevant health care team members. To further support the implementation of pharmacogenetic testing in the hospital setting, it is necessary to promote audit of clinical practice by building hospital‐based registries to facilitate the collection of health care resource use and outcome data that records the clinical uptake of testing. We suggest that well‐conducted economic evaluations, relevant to local practice, are essential pieces of information to guide institutional decision making on how best to develop the appropriate use of pharmacogenetic tests in clinical practice. Drug Dev Res 71: 502–506, 2010. © 2010 Wiley‐Liss, Inc.
Induction of transplantation tolerance converts potential effector T cells into graft‐protective regulatory T cells
Authors: Francis Ross S. , Feng Gang , Tha‐In Thanyalak , Lyons Ian S. , Wood Kathryn J. , Bushell Andrew 
Published: December 2010

AbstractNaturally occurring FOXP3+CD4+ Treg have a crucial role in self‐tolerance. The ability to generate similar populations against alloantigens offers the possibility of preventing transplant rejection without indefinite global immunosuppression. Exposure of mice to donor alloantigens combined with anti‐CD4 antibody induces operational tolerance to cardiac allografts, and generates Treg that prevent skin and islet allograft rejection in adoptive transfer models. If protocols that generate Treg in vivo are to be developed in the clinical setting it will be important to know the origin of the Treg population and the mechanisms responsible for their generation. In this study, we demonstrate that graft‐protective Treg arise in vivo both from naturally occurring FOXP3+CD4+ Treg and from non‐regulatory FOXP3−CD4+ cells. Importantly, tolerance induction also inhibits CD4+ effector cell priming and T cells from tolerant mice have impaired effector function in vitro. Thus, adaptive tolerance induction shapes the immune response to alloantigen by converting potential effector cells into graft‐protective Treg and by expanding alloreactive naturally occurring Treg. In relation to clinical tolerance induction, the data indicate that while the generation of alloreactive Treg may be critical for long‐term allograft survival without chronic immunosuppression, successful protocols will also require strategies that target potential effector cells.
A natural protective function of invariant NKT cells in a mouse model of innate‐cell‐driven lung inflammation
Authors: Bourgeois Elvire A. , Levescot Anaïs , Diem Séverine , Chauvineau Angélique , Bergès Hortense , Milpied Pierre , Lehuen Agnès , Damotte Diane , Gombert Jean‐Marc , Schneider Elke , Girard Jean‐Philippe , Gourdy Pierre , Herbelin André 
Published: December 2010

AbstractActivation of invariant natural killer T (iNKT) cells by treatment with their α‐galactosyl ceramide ligand provides therapeutic benefits in several immune inflammatory settings. Given the artificial nature of this stimulation, the natural regulatory functions of iNKT remain uncertain. Addressing this issue in a mouse model of innate‐cell‐driven lung inflammation induced by the cytokine/alarmin IL‐33 that targets iNKT cells, we found that eosinophil and neutrophil recruitment was markedly increased in treated iNKT cell‐deficient (Jα18 KO) mice, as was the local production of eotaxin and keratinocyte chemoattractant chemokines. By contrast, lung inflammation decreased after adoptive transfer of iNKT cells, which restored the WT inflammatory response in Jα18 KO mice. Finally, we established that this natural anti‐inflammatory function of iNKT cells depends on their IFN‐γ production and on endogenous IL‐12. Our study provides the first evidence of a protective role of iNKT cells during lung inflammation that does not require pharmacological TCR engagement.