bluuebunny/crossref_metadata_2025_split huggingface dataset:
Energy of Midlatitude Transient Eddies in Idealized Simulations of Changed Climates
Authors: O’Gorman Paul A. , Schneider Tapio 
Published: May 2008

Abstract
As the climate changes, changes in static stability, meridional temperature gradients, and availability of moisture for latent heat release may exert competing effects on the energy of midlatitude transient eddies. This paper examines how the eddy kinetic energy in midlatitude baroclinic zones responds to changes in radiative forcing in simulations with an idealized moist general circulation model. In a series of simulations in which the optical thickness of the longwave absorber is varied over a wide range, the eddy kinetic energy has a maximum for a climate with mean temperature similar to that of present-day earth, with significantly smaller values both for warmer and for colder climates. In a series of simulations in which the meridional insolation gradient is varied, the eddy kinetic energy increases monotonically with insolation gradient. In both series of simulations, the eddy kinetic energy scales approximately linearly with the dry mean available potential energy averaged over the baroclinic zones. Changes in eddy kinetic energy can therefore be related to the changes in the atmospheric thermal structure that affect the mean available potential energy.
A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences
Authors: Chica Claudia , Labarga Alberto , Gould Cathryn M , López Rodrigo , Gibson Toby J 
Published: May 2008

Abstract

Background
The structure of many eukaryotic cell regulatory proteins is highly modular. They are assembled from globular domains, segments of natively disordered polypeptides and short linear motifs. The latter are involved in protein interactions and formation of regulatory complexes. The function of such proteins, which may be difficult to define, is the aggregate of the subfunctions of the modules. It is therefore desirable to efficiently predict linear motifs with some degree of accuracy, yet sequence database searches return results that are not significant.

Results
We have developed a method for scoring the conservation of linear motif instances. It requires only primary sequence-derived information (e.g. multiple alignment and sequence tree) and takes into account the degenerate nature of linear motif patterns. On our benchmarking, the method accurately scores 86% of the known positive instances, while distinguishing them from random matches in 78% of the cases. The conservation score is implemented as a real time application designed to be integrated into other tools. It is currently accessible via a Web Service or through a graphical interface.

Conclusion
The conservation score improves the prediction of linear motifs, by discarding those matches that are unlikely to be functional because they have not been conserved during the evolution of the protein sequences. It is especially useful for instances in non-structured regions of the proteins, where a domain masking filtering strategy is not applicable.
RETINOBASE: a web database, data mining and analysis platform for gene expression data on retina
Authors: Kalathur Ravi Kiran Reddy , Gagniere Nicolas , Berthommier Guillaume , Poidevin Laetitia , Raffelsberger Wolfgang , Ripp Raymond , Léveillard Thierry , Poch Olivier 
Published: May 2008

AbstractBackgroundThe retina is a multi-layered sensory tissue that lines the back of the eye and acts at the interface of input light and visual perception. Its main function is to capture photons and convert them into electrical impulses that travel along the optic nerve to the brain where they are turned into images. It consists of neurons, nourishing blood vessels and different cell types, of which neural cells predominate. Defects in any of these cells can lead to a variety of retinal diseases, including age-related macular degeneration, retinitis pigmentosa, Leber congenital amaurosis and glaucoma. Recent progress in genomics and microarray technology provides extensive opportunities to examine alterations in retinal gene expression profiles during development and diseases. However, there is no specific database that deals with retinal gene expression profiling. In this context we have built RETINOBASE, a dedicated microarray database for retina.DescriptionRETINOBASE is a microarray relational database, analysis and visualization system that allows simple yet powerful queries to retrieve information about gene expression in retina. It provides access to gene expression meta-data and offers significant insights into gene networks in retina, resulting in better hypothesis framing for biological problems that can subsequently be tested in the laboratory. Public and proprietary data are automatically analyzed with 3 distinct methods, RMA, dChip and MAS5, then clustered using 2 different K-means and 1 mixture models method. Thus, RETINOBASE provides a framework to compare these methods and to optimize the retinal data analysis. RETINOBASE has three different modules, "Gene Information", "Raw Data System Analysis" and "Fold change system Analysis" that are interconnected in a relational schema, allowing efficient retrieval and cross comparison of data. Currently, RETINOBASE contains datasets from 28 different microarray experiments performed in 5 different model systems: drosophila, zebrafish, rat, mouse and human. The database is supported by a platform that is designed to easily integrate new functionalities and is also frequently updated.ConclusionThe results obtained from various biological scenarios can be visualized, compared and downloaded. The results of a case study are presented that highlight the utility of RETINOBASE. Overall, RETINOBASE provides efficient access to the global expression profiling of retinal genes from different organisms under various conditions.
Improving the accuracy of template-based predictions by mixing and matching between initial models
Authors: Liu Tianyun , Guerquin Michal , Samudrala Ram 
Published: May 2008

AbstractBackgroundComparative modeling is a technique to predict the three dimensional structure of a given protein sequence based primarily on its alignment to one or more proteins with experimentally determined structures. A major bottleneck of current comparative modeling methods is the lack of methods to accurately refine a starting initial model so that it approaches the resolution of the corresponding experimental structure. We investigate the effectiveness of a graph-theoretic clique finding approach to solve this problem.ResultsOur method takes into account the information presented in multiple templates/alignments at the three-dimensional level by mixing and matching regions between different initial comparative models. This method enables us to obtain an optimized conformation ensemble representing the best combination of secondary structures, resulting in the refined models of higher quality. In addition, the process of mixing and matching accumulates near-native conformations, resulting in discriminating the native-like conformation in a more effective manner. In the seventh Critical Assessment of Structure Prediction (CASP7) experiment, the refined models produced are more accurate than the starting initial models.ConclusionThis novel approach can be applied without any manual intervention to improve the quality of comparative predictions where multiple template/alignment combinations are available for modeling, producing conformational models of higher quality than the starting initial predictions.
Heterogeneous distribution of Plasmodium falciparum drug resistance haplotypes in subsets of the host population
Authors: Schoepflin Sonja , Marfurt Jutta , Goroti Mary , Baisor Moses , Mueller Ivo , Felger Ingrid 
Published: May 2008

Abstract

Background
The emergence of drug resistance is a major problem in malaria control. For mathematical modelling of the transmission and spread of drug resistance the determinant parameters need to be identified and measured. The underlying hypothesis is that mutations associated with drug resistance incur fitness costs to the parasite in absence of drug pressure. The distribution of drug resistance haplotypes in different subsets of the host population was investigated. In particular newly acquired haplotypes after radical cure were characterized and compared to haplotypes from persistent infections.

Methods
Mutations associated with antimalarial drug resistance were analysed in parasites from children, adults, and new infections occurring after treatment. Twenty-five known single nucleotide polymorphisms from four Plasmodium falciparum genes associated with drug resistance were genotyped by DNA chip technology.

Results
Haplotypes were found to differ between subsets of the host population. A seven-fold mutated haplotype was significantly reduced in adults compared to children and new infections, whereas parasites harbouring fewer mutations were more frequent in adults.

Conclusion
The reduced frequency of highly mutated parasites in chronic infections in adults is likely a result of fitness costs of drug resistance that increases with number of mutations and is responsible for reduced survival of mutant parasites.
Small-molecule inhibition of proteasome and silencing by vascular endothelial cell growth factor-specific siRNA induce additive antitumor activity in multiple myeloma
Authors: Koldehoff Michael , Beelen Dietrich W , Elmaagacli Ahmet H 
Published: May 2008

AbstractAngiogenesis plays an important role in the pathogenesis and progression in multiple myeloma (MM), and MM cells secrete vascular endothelial growth factor (VEGF), which further promotes proliferation of the tumor cells. Therefore, we evaluated the anti-myeloma effect of VEGF small interfering RNA (siRNA) silencing in MM cells and whether it can be augmented by the additional application of bortezomib directed against the 26S proteasome. After transfection with VEGF siRNA, we observed a reduction of VEGF expression in all studied cell lines: OPM-2, RPMI-8226, INA-6, Jurkat, Raji, and Karpas-299, as well as in cells of MM and lymphoma patients. VEGF siRNA significantly induced apoptosis and inhibited proliferation in OPM-2 cells (P&lt;0.0001), RPMI-8226 (P&lt;0.0001), and INA-6 (P&lt;0.01) versus controls. Cotreatment with VEGF siRNA and bortezomib in MM cells resulted in an exaggerated inhibition of proliferation and induction of apoptosis compared with VEGF siRNA or bortezomib alone (P&lt;0.001). In addition, the combination of VEGF siRNA and bortezomib significantly (P&lt;0.01) reversed multidrug resistance gene 1-dependent resistance of MM cells. Our data suggest that small-molecule inhibition of proteasome and silencing by VEGF-specific siRNA may be associated with an additive antitumor activity and might be a suitable target for new, therapeutic strategies using RNA interference in MM.
Gene-Centric Genomewide Association Study via Entropy
Authors: Cui Yuehua , Kang Guolian , Sun Kelian , Qian Minping , Romero Roberto , Fu Wenjiang 
Published: May 2008

AbstractGenes are the functional units in most organisms. Compared to genetic variants located outside genes, genic variants are more likely to affect disease risk. The development of the human HapMap project provides an unprecedented opportunity for genetic association studies at the genomewide level for elucidating disease etiology. Currently, most association studies at the single-nucleotide polymorphism (SNP) or the haplotype level rely on the linkage information between SNP markers and disease variants, with which association findings are difficult to replicate. Moreover, variants in genes might not be sufficiently covered by currently available methods. In this article, we present a gene-centric approach via entropy statistics for a genomewide association study to identify disease genes. The new entropy-based approach considers genic variants within one gene simultaneously and is developed on the basis of a joint genotype distribution among genetic variants for an association test. A grouping algorithm based on a penalized entropy measure is proposed to reduce the dimension of the test statistic. Type I error rates and power of the entropy test are evaluated through extensive simulation studies. The results indicate that the entropy test has stable power under different disease models with a reasonable sample size. Compared to single SNP-based analysis, the gene-centric approach has greater power, especially when there is more than one disease variant in a gene. As the genomewide genic SNPs become available, our entropy-based gene-centric approach would provide a robust and computationally efficient way for gene-based genomewide association study.
Altered Dosage and Mislocalization of Histone H3 and Cse4p Lead to Chromosome Loss in Saccharomyces cerevisiae
Authors: Au Wei-Chun , Crisp Matthew J , DeLuca Steven Z , Rando Oliver J , Basrai Munira A 
Published: May 2008

Abstract
Cse4p is an essential histone H3 variant in Saccharomyces cerevisiae that defines centromere identity and is required for proper segregation of chromosomes. In this study, we investigated phenotypic consequences of Cse4p mislocalization and increased dosage of histone H3 and Cse4p, and established a direct link between histone stoichiometry, mislocalization of Cse4p, and chromosome segregation. Overexpression of the stable Cse4p mutant, cse4K16R, resulted in its mislocalization, increased association with chromatin, and a high rate of chromosome loss, all of which were suppressed by constitutive expression of histone H3 (Δ16H3). We determined that Δ16H3 did not lead to increased chromosome loss; however, increasing the dosage of histone H3 (GALH3) resulted in significant chromosome loss due to reduced levels of centromere (CEN)-associated Cse4p and synthetic dosage lethality (SDL) in kinetochore mutants. These phenotypes were suppressed by GALCSE4. We conclude that the chromosome missegregation of GALcse4K16R and GALH3 strains is due to mislocalization and a functionally compromised kinetochore, respectively. Suppression of these phenotypes by histone Δ16H3 and GALCSE4 supports the conclusion that proper stoichiometry affects the localization of histone H3 and Cse4p and is thus essential for accurate chromosome segregation.
EMLA Cream and Nitrous Oxide to Alleviate Pain Induced by Palivizumab (Synagis) Intramuscular Injections in Infants and Young Children
Authors: Carbajal Ricardo , Biran Valérie , Lenclen Richard , Epaud Ralph , Cimerman Patricia , Thibault Pascale , Annequin Daniel , Gold Francis , Fauroux Brigitte 
Published: May 2008

OBJECTIVE. Palivizumab (Synagis [Abbot Laboratories, Kent, United Kingdom]) is recommended for the prevention of severe lower respiratory tract infections caused by respiratory syncytial virus in infants at high risk. These injections are very painful, and currently the use of analgesics is not systematic. The objective of this study was to compare the efficacy of EMLA with premixed 50% nitrous oxide/oxygen, used alone or combined with EMLA, for pain alleviation during palivizumab injections.METHODS. This randomized, double-blind, multicenter study included children who were younger than 24 months. Each child randomly received during the first 3 monthly injections 3 different analgesic interventions: (1) EMLA: application of EMLA plus air inhalation; (2) nitrous oxide/oxygen: inhalation of 50/50 nitrous oxide/oxygen plus application of a placebo cream; and (3) nitrous oxide/oxygen plus EMLA: inhalation of 50/50 nitrous oxide/oxygen plus application of EMLA. Each child was his or her own control. Procedural pain was assessed through videotapes with the Modified Behavioral Pain Scale. The procedure itself was subdivided in 2 periods: (1) injection and (2) recovery (first 30 seconds after the removal of the needle). Modified Behavioral Pain Scale scores over time (injection and recovery periods) and among treatments were compared by repeated-measures analysis of variance.RESULTS. Fifty-five children were included. Mean ± SD Modified Behavioral Pain Scale pain scores for EMLA, nitrous oxide/oxygen, and nitrous oxide/oxygen plus EMLA were, respectively, 9.3 ± 1.0, 8.8 ± 1.2, and 8.2 ± 1.8 during the injection and 7.8 ± 1.7, 7.4 ± 1.9, and 6.9 ± 2.4 during the recovery period. A significant time and treatment effect in favor of the combined nitrous oxide/oxygen plus EMLA was observed.CONCLUSIONS. The administration of 50/50 nitrous oxide/oxygen to infants and young children is effective in decreasing the pain associated with palivizumab intramuscular injections. The combined nitrous oxide/oxygen plus EMLA cream was more effective than either EMLA cream or nitrous oxide/oxygen alone.
Palmitate Impairs and Eicosapentaenoate Restores Insulin Secretion Through Regulation of SREBP-1c in Pancreatic Islets
Authors: Kato Toyonori , Shimano Hitoshi , Yamamoto Takashi , Ishikawa Mayumi , Kumadaki Shin , Matsuzaka Takashi , Nakagawa Yoshimi , Yahagi Naoya , Nakakuki Masanori , Hasty Alyssa H. , Takeuchi Yoshinori , Kobayashi Kazuto , Takahashi Akimitsu , Yatoh Shigeru , Suzuki Hiroaki , Sone Hirohito , Yamada Nobuhiro 
Published: May 2008

OBJECTIVE—Chronic exposure to fatty acids causes β-cell failure, often referred to as lipotoxicity. We investigated its mechanisms, focusing on contribution of SREBP-1c, a key transcription factor for lipogenesis.
RESEARCH DESIGN AND METHODS—We studied in vitro and in vivo effects of saturated and polyunsaturated acids on insulin secretion, insulin signaling, and expression of genes involved in β-cell functions. Pancreatic islets isolated from C57BL/6 control and SREBP-1–null mice and adenoviral gene delivery or knockdown systems of related genes were used.
RESULTS—Incubation of C57BL/6 islets with palmitate caused inhibition of both glucose- and potassium-stimulated insulin secretion, but addition of eicosapentaenoate (EPA) restored both inhibitions. Concomitantly, palmitate activated and EPA abolished both mRNA and nuclear protein of SREBP-1c, accompanied by reciprocal changes of SREBP-1c target genes such as insulin receptor substrate-2 (IRS-2) and granuphilin. These palmitate-EPA effects on insulin secretion were abolished in SREBP-1–null islets. Suppression of IRS-2/Akt pathway could be a part of the downstream mechanism for the SREBP-1c–mediated insulin secretion defect because adenoviral constitutively active Akt compensated it. Uncoupling protein-2 (UCP-2) also plays a crucial role in the palmitate inhibition of insulin secretion, as confirmed by knockdown experiments, but SREBP-1c contribution to UCP-2 regulation was partial. The palmitate-EPA regulation of insulin secretion was similarly observed in islets from C57BL/6 mice pretreated with dietary manipulations. Furthermore, administration of EPA to diabetic KK-Ay mice ameliorated impairment of insulin secretion in their islets.
CONCLUSIONS—SREBP-1c plays a dominant role in palmitate-mediated insulin secretion defect, and EPA prevents it through SREBP-1c inhibition, implicating a therapeutic potential for treating diabetes related to lipotoxicity.
Hierarchical Assembly of Organic/Inorganic Building Molecules with π–π Interactions
Authors: Yang Lu , Peng Huisheng , Huang Kun , Mague Joel T. , Li Hexing , Lu Yunfeng 
Published: May 2008

AbstractHierarchical assemblies of perylenetetracarboxylic diimide bridged silsesquioxane (PDBS) with controlled structure at multi‐length scale are studied using both experimental and computational methods. The organization process spans multi‐length scales and includes three continuous steps: 1) stacking of the preprogrammed molecules into small clusters, 2) growing of the small clusters into nanoscale building blocks with various sizes and shapes depending on the experimental conditions, and 3) aggregation of nanoscale building blocks into micro‐ or macro‐scale assemblies. The main factors determining the assembly morphology are the second and third steps, which can be controlled by varying the experimental conditions, such as solution drying rate, solvent composition, and PDBS concentration. Despite the different morphologies, all of these assemblies possess highly ordered lamellar structure. It is found that incorporating perylenetetracarboxylic diimide (PD) moieties into the highly ordered silica network endows the PD components with high thermal and mechanical stability, as well as improved optical and electronic properties.
Computer evaluation of hydrogel‐based systems for diabetes closed loop treatment
Authors: Sánchez‐Chávez Irma Y. , Martínez‐Chapa Sergio O. , Peppas Nicholas A. 
Published: May 2008

AbstractHydrogels provide the multifunctionality of smart materials and the applicability to medical regulatory systems. Hydrogel membranes that incorporate glucose oxidase for the closed loop treatment of type 1 diabetes mellitus are characterized and modeled. The Sorensen compartmental model is extended to represent the treatment system of a diabetic patient. The performance of the system closed by a hydrogel‐based device is explored and compared to the dynamic behavior of a conventional scheme with an explicit controller element. Anionic and cationic hydrogels are discussed for insulin delivery application. Simulations demonstrate limitations in the range of swelling and contraction of hydrogels in a physiological environment due to the Donnan equilibrium effect. Results show the reduction of peak glucose levels and a basal insulin delivery from a hydrogel membrane system. The evaluation of ionic hydrogel membrane macrosystems prompts the consideration of detected pros and cons using different hydrogels, structures and scales. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Patterns of occurrence and concordance between subjective and objective hot flashes among Muslim and Hindu women in Sylhet, Bangladesh
Authors: Sievert Lynnette Leidy , Begum Khurshida , Sharmeen Taniya , Chowdhury Osul , Muttukrishna Shanthi , Bentley Gillian 
Published: May 2008

AbstractThis study examined the pattern of occurrence and the rate of concordance between objective hot flashes measured by sternal skin conductance and the subjective experience of “gorom vap laga” (feeling steaming hot) among Muslim and Hindu women living in Sylhet, Bangladesh. Participants were aged 40–55, not pregnant or lactating, not using hormone therapy, and with no history of hysterectomy. Thirty women wore an ambulatory hot flash monitor for 8 h on average, from mid‐morning to early evening. True positive, false negative, and false positive measures of hot flashes were examined in relation to demographic, reproductive, and lifestyle variables. On body diagrams, women were most likely to indicate hot flashes on the top of their head (64%) and upper chest (68%). The greatest number of objective hot flashes occurred during the hour of 17:00, perhaps due to the heat of the day, and the clothing and activity associated with prayer. Muslim participants demonstrated more objective hot flashes per woman than Hindu participants (1.5 vs. 0.1, P < 0.05), and Muslims had more false positive measures (86%) compared with Hindu participants (0%, P = 0.06). Among all women who reported subjective hot flashes (n = 19), the proportion of true positive scores was 19%. Overall, the frequency of objective hot flashes was low compared with reports from studies in the United States. The pattern of sweating assessed by body diagrams was not associated with variation in hot flash experience. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.