bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of SNPs associated with variola virus virulence
Authors: Hoen Anne Gatewood , Gardner Shea N , Moore Jason H 
Published: February 2013

Abstract

Background
Decades after the eradication of smallpox, its etiological agent, variola virus (VARV), remains a threat as a potential bioweapon. Outbreaks of smallpox around the time of the global eradication effort exhibited variable case fatality rates (CFRs), likely attributable in part to complex viral genetic determinants of smallpox virulence. We aimed to identify genome-wide single nucleotide polymorphisms associated with CFR. We evaluated unadjusted and outbreak geographic location-adjusted models of single SNPs and two- and three-way interactions between SNPs.

Findings
Using the data mining approach multifactor dimensionality reduction (MDR), we identified five VARV SNPs in models significantly associated with CFR. The top performing unadjusted model and adjusted models both revealed the same two-way gene-gene interaction. We discuss the biological plausibility of the influence of the SNPs identified these and other significant models on the strain-specific virulence of VARV.

Conclusions
We have identified genetic loci in the VARV genome that are statistically associated with VARV virulence as measured by CFR. While our ability to infer a causal relationship between the specific SNPs identified in our analysis and VARV virulence is limited, our results suggest that smallpox severity is in part associated with VARV strain variation and that VARV virulence may be determined by multiple genetic loci. This study represents the first application of MDR to the identification of pathogen gene-gene interactions for predicting infectious disease outbreak severity.
A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome
Authors: Blandin Gaëlle , Marchand Sylvie , Charton Karine , Danièle Nathalie , Gicquel Evelyne , Boucheteil Jean-Baptiste , Bentaib Azéddine , Barrault Laetitia , Stockholm Daniel , Bartoli Marc , Richard Isabelle 
Published: February 2013

Abstract

Background
The complexity of the skeletal muscle and the identification of numerous human disease-causing mutations in its constitutive proteins make it an interesting tissue for proteomic studies aimed at understanding functional relationships of interacting proteins in both health and diseases.

Method
We undertook a large-scale study using two-hybrid screens and a human skeletal-muscle cDNA library to establish a proteome-scale map of protein-protein interactions centered on proteins involved in limb-girdle muscular dystrophies (LGMD). LGMD is a group of more than 20 different neuromuscular disorders that principally affect the proximal pelvic and shoulder girdle muscles.

Results and conclusion
The interaction network we unraveled incorporates 1018 proteins connected by 1492 direct binary interactions and includes 1420 novel protein-protein interactions. Computational, experimental and literature-based analyses were performed to assess the overall quality of this network. Interestingly, LGMD proteins were shown to be highly interconnected, in particular indirectly through sarcomeric proteins. In-depth mining of the LGMD-centered interactome identified new candidate genes for orphan LGMDs and other neuromuscular disorders. The data also suggest the existence of functional links between LGMD2B/dysferlin and gene regulation, between LGMD2C/γ-sarcoglycan and energy control and between LGMD2G/telethonin and maintenance of genome integrity. This dataset represents a valuable resource for future functional investigations.
Generation and validation of a zebrafish model of EAST (Epilepsy, ataxia, sensorineural deafness and tubulopathy) syndrome
Authors: Mahmood Fahad , Mozere Monika , Zdebik Anselm A. , Stanescu Horia C. , Tobin Jonathan , Beales Philip L. , Kleta Robert , Bockenhauer Detlef , Russell Claire 
Published: February 2013

Summary
Recessive mutations in KCNJ10, which encodes an inwardly rectifying potassium channel, were recently identified as the cause of EAST syndrome, a severe and disabling multi-organ disorder consisting of epilepsy, ataxia, sensorineural deafness and tubulopathy that becomes clinically apparent with seizures in infancy. A Kcnj10 knockout mouse shows postnatal mortality and is therefore not suitable for drug discovery. Because zebrafish are ideal for in vivo screening for potential therapeutics, we tested whether kcnj10 knockdown in zebrafish would fill this need. We cloned zebrafish kcnj10 and demonstrated that its function is equivalent to that of human KCNJ10. We next injected splice- and translation-blocking kcnj10 antisense morpholino oligonucleotides and reproduced the cardinal symptoms of EAST syndrome – ataxia, epilepsy and renal tubular defects. Several of these phenotypes could be assayed in an automated manner. We could rescue the morphant phenotype with complementary RNA (cRNA) encoding human wild-type KCNJ10, but not with cRNA encoding a KCNJ10 mutation identified in individuals with EAST syndrome. Our results suggest that zebrafish will be a valuable tool to screen for compounds that are potentially therapeutic for EAST syndrome or its individual symptoms. Knockdown of kcnj10 represents the first zebrafish model of a salt-losing tubulopathy, which has relevance for blood pressure control.
Preparation of Hydroxyapatite-coated Anatase by Photoinduced Superhydrophilic Reaction of TiO2 for Water Purification
Authors: Sugita Tsuyoshi , Mori Masanobu , Nakane Hisashi , Mase Akinori , Itabashi Hideyuki 
Published: February 2013

Abstract
Hydroxyapatite coated on TiO2 for use as a photocatalyst for water purification was synthesized by using the superhydrophilicity of TiO2. The hydroxyapatite formed on TiO2 under UV irradiation with high crystallization in 1 h. The isoelectric point of the hydroxyapatite-coated TiO2 was shifted to acidic pH, and the aggregates formed in aqueous solution at pH 7 were smaller than those of anatase TiO2. Consequently, in water purification tests, the proposed photocatalyst effectively decomposed dimethyl sulfoxide and Methylene Blue in water.
A Novel Approach for Determining the Proportions of Pyrolysis and Hydrolysis in the Degradation of Poly(ethylene terephthalate) in 18O-Labeled Steam
Authors: Kumagai Shogo , Morohoshi Yuto , Grause Guido , Kameda Tomohito , Yoshioka Toshiaki 
Published: February 2013

Abstract
The proportions of pyrolysis and hydrolysis in poly(ethylene terephthalate) (PET) degradation were determined from the decomposition of PET in 18O-labeled steam, producing labeled and unlabeled terephthalic acid. At a 100 vol % steam concentration at 400 °C, 74% of the ester bonds were pyrolyzed and 26% were hydrolyzed, as determined by gas chromatography-mass spectrometry. In addition, thermogravimetric analysis revealed the activation energy to be 199 kJ mol−1 under pyrolytic conditions, decreasing with increasing steam concentration, and reaching a minimum of 132 kJ mol−1 at 75 vol %.
Surfactant-free Synthesis and Growing Process of One-dimensional Mg–Al Layered Double Hydroxide Nanobelts
Authors: Ding Peng , Kang Bai , Tang Shengfu , Song Na , Shi Liyi 
Published: February 2013

Abstract
One-dimensional MgAl–CO3 layered double hydroxide (LDH) nanobelts were synthesized by a hydrothermal method in an aqueous solution system without templates. The study showed that the reaction time, reaction temperature, and aging process were the key factors for obtaining LDH nanobelts. Hydrothermal reaction at 60 °C for 48 h favored the growth of nanobelts of width 50–150 nm and length 1000–2000 nm. The nanobelts had the characteristic structures of CO32− intercalated LDHs. Moreover, a tentative mechanism was proposed to explain the evolution of nanobelts in the present system.
Effect of Optical Purity of C3-Symmetric Chiral Tris-ureas on Supramolecular Gel Formation
Authors: Nakagawa Tomoe , Amakatsu Mawo , Munenobu Kanako , Fujii Hiromitsu , Yamanaka Masamichi 
Published: February 2013

Abstract
Homochiral C3-symmetric tris-ureas 1–3 and heterochiral tris-urea 4 were synthesized. The homochiral tris-ureas 1–3 acted as low-molecular-weight gelators for various organic solvents. The optical purities of the tris-ureas strongly influenced their gelation. External chiral molecules influenced chiral supramolecular gel formation of chiral tris-ureas.
Toward a Liberal Theory of Punishment: Locke, Property, and Individualism
Authors: Donoso Alfonso 
Published: February 2013

AbstractBy offering a critical analysis of Nicolás Maloberti’s recent theory and justification of punishment, this article accounts for a series of principles and considerations that any liberal and Lockean theory of punishment must take seriously. This article contends that Locke’s conception of the state – an institution grounded on the right to punish violators of natural rights – and the basic character of the right to property within Locke’s scheme of rights are elements that should lead us to affirm that no genuine liberal theory of punishment can dispense with the political character of the right to punish.
Higher Levels of Neanderthal Ancestry in East Asians than in Europeans
Authors: Wall Jeffrey D , Yang Melinda A , Jay Flora , Kim Sung K , Durand Eric Y , Stevison Laurie S , Gignoux Christopher , Woerner August , Hammer Michael F , Slatkin Montgomery 
Published: February 2013

AbstractNeanderthals were a group of archaic hominins that occupied most of Europe and parts of Western Asia from ∼30,000 to 300,000 years ago (KYA). They coexisted with modern humans during part of this time. Previous genetic analyses that compared a draft sequence of the Neanderthal genome with genomes of several modern humans concluded that Neanderthals made a small (1–4%) contribution to the gene pools of all non-African populations. This observation was consistent with a single episode of admixture from Neanderthals into the ancestors of all non-Africans when the two groups coexisted in the Middle East 50–80 KYA. We examined the relationship between Neanderthals and modern humans in greater detail by applying two complementary methods to the published draft Neanderthal genome and an expanded set of high-coverage modern human genome sequences. We find that, consistent with the recent finding of Meyer et al. (2012), Neanderthals contributed more DNA to modern East Asians than to modern Europeans. Furthermore we find that the Maasai of East Africa have a small but significant fraction of Neanderthal DNA. Because our analysis is of several genomic samples from each modern human population considered, we are able to document the extent of variation in Neanderthal ancestry within and among populations. Our results combined with those previously published show that a more complex model of admixture between Neanderthals and modern humans is necessary to account for the different levels of Neanderthal ancestry among human populations. In particular, at least some Neanderthal–modern human admixture must postdate the separation of the ancestors of modern European and modern East Asian populations.
Limited RNA Editing in Exons of Mouse Liver and Adipose
Authors: Lagarrigue Sandrine , Hormozdiari Farhad , Martin Lisa J , Lecerf Frédéric , Hasin Yehudit , Rau Christoph , Hagopian Raffi , Xiao Yu , Yan Jun , Drake Thomas A , Ghazalpour Anatole , Eskin Eleazar , Lusis Aldons J 
Published: February 2013

Abstract
Several studies have investigated RNA–DNA differences (RDD), presumably due to RNA editing, with conflicting results. We report a rigorous analysis of RDD in exonic regions in mice, taking into account critical biases in RNA-Seq analysis. Using deep-sequenced F1 reciprocal inbred mice, we mapped 40 million RNA-Seq reads per liver sample and 180 million reads per adipose sample. We found 7300 apparent hepatic RDDs using a multiple-site mapping procedure, compared with 293 RDD found using a unique-site mapping procedure. After filtering for repeat sequence, splice junction proximity, undirectional strand, and extremity read bias, 63 RDD remained. In adipose tissue unique-site mapping identified 1667 RDD, and after applying the same four filters, 188 RDDs remained. In both tissues, the filtering procedure increased the proportion of canonical (A-to-I and C-to-U) editing events. The genomic DNA of 12 RDD sites among the potential 63 hepatic RDD was tested by Sanger sequencing, three of which proved to be due to unreferenced SNPs. We validated seven liver RDD with Sequenom technology, including two noncanonical, Gm5424 C-to-I(G) and Pisd I(G)-to-A RDD. Differences in diet, sex, or genetic background had very modest effects on RDD occurrence. Only a small number of apparent RDD sites overlapped between liver and adipose, indicating a high degree of tissue specificity. Our findings underscore the importance of properly filtering for bias in RNA-Seq investigations, including the necessity of confirming the DNA sequence to eliminate unreferenced SNPs. Based on our results, we conclude that RNA editing is likely limited to hundreds of events in exonic RNA in liver and adipose.
A Longitudinal Study of Left Ventricular Function and Structure from CKD to ESRD
Authors: Bansal Nisha , Keane Martin , Delafontaine Patrice , Dries Daniel , Foster Elyse , Gadegbeku Crystal A. , Go Alan S. , Hamm L. Lee , Kusek John W. , Ojo Akinlolu O. , Rahman Mahboob , Tao Kaixiang , Wright Jackson T. , Xie Dawei , Hsu, Chi-yuan 
Published: February 2013

Summary

Background and objectives
Abnormal left ventricular structure and function are associated with increased risk of adverse outcomes among patients with CKD and ESRD. A better understanding of changes in left ventricular mass and ejection fraction during the transition from CKD to ESRD may provide important insights to opportunities to improve cardiac outcomes.

Design, setting, participants, & measurements
This was a longitudinal study of a subset of participants of the Chronic Renal Insufficiency Cohort who were enrolled from 2003 to 2007 and followed through January of 2011. Participants were included if they had serial echocardiograms performed at advanced CKD (defined as estimated GFR<20 ml/min per 1.73 m2) and again after ESRD (defined as need for hemodialysis or peritoneal dialysis).

Results
A total of 190 participants (44% female, 66% black) had echocardiograms during advanced CKD and after ESRD. Mean (SD) estimated GFR at advanced CKD was 16.9 (3.5) ml/min per 1.73 m2. Mean (SD) time between the advanced CKD echocardiogram and ESRD echocardiogram was 2.0 (1.0) years. There was no significant change in left ventricular mass index (62.3–59.5 g/m2.7, P=0.10) between advanced CKD and ESRD; however, ejection fraction significantly decreased (53%–50%, P=0.002). Interactions for age, race, dialysis modality, and diabetes status were not significant (P>0.05).

Conclusions
Mean left ventricular mass index did not change significantly from advanced CKD to ESRD; however, ejection fraction declined during this transition period. Although left ventricular mass index is fixed by advanced stages of CKD, ejection fraction decline during more advanced stages of CKD may be an important contributor to cardiovascular disease and mortality after dialysis.
Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion
Authors: Polidori David , Sha Sue , Mudaliar Sunder , Ciaraldi Theodore P. , Ghosh Atalanta , Vaccaro Nicole , Farrell Kristin , Rothenberg Paul , Henry Robert R. 
Published: February 2013

OBJECTIVE
Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption.

RESEARCH DESIGN AND METHODS
This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal.

RESULTS
Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P &lt; 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0–6h, 18.2 ± 5.6 vs. &lt;0.2 g; P &lt; 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P &lt; 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was &lt;6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups.

CONCLUSIONS
Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition.
Perceptions of Usability and Design for Prefilled Insulin Delivery Devices for Patients With Type 2 Diabetes
Authors: Heron Louise , Reaney Matthew , Hermanns Norbert , Abetz Linda , Gregg Laura 
Published: February 2013

Although many patients with type 2 diabetes are initially managed through lifestyle modification, most eventually require insulin therapy. However, insulin initiation is often delayed because of factors such as patients' resistance to insulin therapy and worries about injections. Such delays affect glycemic control, have a direct effect on patient encounters, and may affect medication adherence. Insulin pen delivery systems may address some of these concerns.
This study had two phases. First, semi-structured qualitative interviews were conducted to identify the most important features of insulin delivery devices for prandial use from the perspective of patients (n = 8) and health care professionals (HCPs; n = 10). From phase 1, a 26-item questionnaire was developed. In phase 2, patients (n = 33 insulin naive, n = 78 pen users) and HCPs (n = 151) were asked to indicate the most important features to them in insulin delivery devices. Patients then simulated injection using three different pens (SoloSTAR, KwikPen, and FlexPen) and ranked them based on the same features.
The most important features were knowing that the entire dose has been injected, ease of reading the dose correctly, and ease of correcting if the dose is over-dialed. In the simulation study, KwikPen and SoloSTAR scored significantly higher (paired t test, P &lt; 0.05) than FlexPen on “knowing if you have injected the entire dose” (mean score out of 10: KwikPen, 8.9; SoloSTAR, 8.6; and FlexPen, 8.4). No other significant differences among the pens were noted in usability or design, and the mean ranking (from 1 to 3) of the pens was similar (KwikPen, 2.0; FlexPen, 2.1; and SoloSTAR, 1.9). By identifying which insulin delivery pens offer these features, HCPs can choose the most appropriate delivery device for patients, which may lead to earlier insulin initiation, greater patient adherence, and better clinical outcomes.
Works of A.A. Samarskii on Computational Mathematics
Authors: Vabishchevich P.N. 
Published: February 2013

Abstract This is a review of the main results in computational mathematics that
were obtained by the eminent Russian mathematician Alexander Andreevich Samarskii
(February 19, 1919 – February 11, 2008). His outstanding research output addresses
all the main questions that arise in the construction and justification of algorithms for
the numerical solution of problems from mathematical physics.
The remarkable works of A.A. Samarskii include statements of the main principles re-
quired in the construction of difference schemes, rigorous mathematical proofs of the
stability and convergence of these schemes, and also investigations of their algorith-
mic implementation. A.A. Samarskii and his collaborators constructed and applied in
practical calculations a large number of algorithms for solving various problems from
mathematical physics, including thermal physics, gas dynamics, magnetic gas dynam-
ics, plasma physics, ecology and other important models from the natural sciences.
A Metod with a Controllable Exponential Convergence Rate for Nonlinear Differential Operator Equations
Authors: Gavrilyuk I.P. , Lazurchak I. I. , Makarov V. L. , Sytnyk D. 
Published: February 2013

AbstractWe propose a new analytical-numerical method with an embedded
convergence control mechanism for solving nonlinear operator differential equations.
The method provides the exponential convergence rate. A numerical example confirms
the theoretical results.
The International Diffusion Of European Alcohol Research / Mednarodna Razpršenost Evropskih Raziskav O Alkoholu
Authors: Robles Noemi , Matrai Silvia , Carral Bielsa Vanesa , Colom Joan , Gual Antoni 
Published: February 2013

Abstract
Background: Europe presents the highest rates of alcohol consumption per inhabitant, with an impact exceeding 6% of the DALYs lost. However, European researchers claim that most of the research in the alcohol field is conducted outside Europe. In order to assess this claim, a review of international indexed publications on alcohol marketing and availability, two cornerstones of alcohol public health policy, was performed.
Methods: A systematic search on Medline (1990-2009) was conducted by two independent researchers in order to identify articles that studied the availability or marketing of alcoholic beverages. The publication year and country of affiliation of the first author were recorded. The type and number of publications were classified according to the geographic area where the research was conducted.
Results: Of the 990 retrieved articles on availability, 214 were found relevant; of the 828 articles obtained for marketing, 249 were classified as relevant. Most of the alcohol availability- and marketing-related articles were published in the USA (52.3% and 59.0%, respectively). A total of 22.5% of the availability studies and 15.7% of the marketing studies were published by a first author affiliated to a European country. The European alcohol-related references have been generated mostly in the UK, the Scandinavian countries and the Netherlands (73.4% of all European publications).
Conclusion: Despite the impact of alcohol in Europe, most of the research is conducted in other countries. Moreover, the volume of research is unequal among the European countries as well. European public health research in the alcohol field should be encouraged, involving countries with scant or non-existent research.