bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Self‐Help, Language, and Academic Skills in Persons With Down Syndrome
Authors: de Graaf Gert , de Graaf Erik 
Published: June 2016

AbstractUsing visual analysis by means of scatterplots, correlational analysis, and linear regressions, the authors explored the skills of individuals with Down syndrome in the areas of self‐help, language, academics, and computer skills. By combining data of several Dutch studies, they obtained 1,252 different observations made by parents on 862 individuals, aged <1–35 years. Research shows advancement in language skills up to the age of 12, with plateauing afterward. In contrast, self‐help skills still increase in adolescence and young adulthood. Academics and computer skills improve up to the age of 14. However, less developed academic skills (and computer skills) of adolescents and young adults appear to be a generational difference, rather than a loss of acquired skills. In their analysis, the authors differentiated between students with a primarily regular school career vs. those with a primarily special school career. In addition, in both groups, the studies were differentiated between students with an IQ >50 vs. an IQ between 35 and 50. The comparison between the various subgroups revealed that children with special education backgrounds in the higher IQ range demonstrated less advanced academic skills than children with regular education backgrounds in the lower IQ range. This suggests that regular education is more stimulating for academic skill development. Using age, “school career,” and IQ (<35; 35–50; 50–60; 60–70; >70) as predictors, regressions confirmed this conclusion. The authors conclude that their analyses show that the shift in the early 1990s in the Netherlands toward more inclusion in education for students with Down syndrome has led to better outcomes in academic skill development for these students.
Effect of Taekwondo Training on Lower Body Strength and Balance in Young Adults with Down Syndrome
Authors: Carter Kathy , Horvat Michael 
Published: June 2016

AbstractResearch with individuals with Down syndrome (DS) suggests that increasing strength and balance may lead to increases in independence and self‐reliance. Taekwondo has been shown to increase strength and balance in typically developing (TD) individuals. A study was undertaken to determine whether Taekwondo training can improve lower body strength and balance of young adults with DS. Forty‐four adults with DS aged 21–30 years were assigned to either taekwondo classes 2 days/weeks for 10 weeks (n = 22) or a control group (n = 22). Measurements were taken prior to training, after 5 weeks and after 10 weeks of training, and after a 5 week detraining period. Strength was measured utilizing a hand‐held dynamometer. Balance tests utilized the modified Clinical Test for Sensory Integration and Balance (mCTSIB) with eyes open and closed, whereas dynamic balance was measured utilizing a limits of stability (LOS) test. A repeated measures MANOVA (significance level set at p < .05) was utilized to determine differences between groups over time for each of the three assessments. It was found that there was a significant mean increase in lower body strength after 5 weeks (pre: 142.1 lbs ± 52.4; 5 week: 197.7 lbs ± 71.2), and an additional increase after 10 weeks of training (10 week: 227.9 lbs ± 74.9). A decrease in strength was shown after detraining (188.5 lbs ± 63.7). Strength measures for the control group remained unchanged. There were no significant differences seen between groups in static or dynamic balance. The authors concluded that Taekwondo can be an effective method to increase strength of individuals with DS. Additional research is needed to determine if these strength changes lead to benefits related to physical function and independence.
Comprehensive In Situ Analysis of Arteriolar Network Geometry and Topology in Rat Gluteus Maximus Muscle
Authors: Al Tarhuni Mohammed , Goldman Daniel , Jackson Dwayne N. 
Published: June 2016

AbstractObjectivesTo provide detailed geometric and topological descriptions of the rat gluteus maximus arteriolar network, and to measure the distribution of diameters and lengths as well as their associated variability within and between networks.MethodsComplete arteriolar networks arising from feed artery (inferior gluteal artery) to terminal branches were imaged under baseline conditions, using IVVM. Photomontages of complete networks were assembled and evaluated offline for measurements of geometry and topology. Single‐line (skeletonized) tracings of the networks were made for fractal analysis.ResultsDiameters and lengths decreased with increasing topological order (centrifugal), while number of elements increased with increasing order. Horton's laws were shown to be valid within the arteriolar networks of the rat GM. Inter‐network variability in diameter (~5–22%) and length (~17–30%) at each order was generally lower than the corresponding intra‐network variability in diameter (~10–48%) and length (~39–106%).ConclusionsData presented in this study provide crucial quantitative analysis of complete arteriolar networks within healthy skeletal muscle, and may serve as ideal experimental inputs for future theoretical studies of skeletal muscle microvascular structure and function.
Mechanosensitive Gq/11 Protein–Coupled Receptors Mediate Myogenic Vasoconstriction
Authors: Mederos y Schnitzler Michael , Storch Ursula , Gudermann Thomas 
Published: June 2016

AbstractMyogenic vasoconstriction (Bayliss effect) is mediated by vascular smooth muscle cells (VSMCs) of small resistance arteries sensing mechanical forces. During the last three decades, several proteins have been proposed as VSMC mechanosensors. Our previous studies highlighted agonist‐independent mechanical activation of Gq/11 protein‐coupled receptors (Gq/11PCRs) in VSMCs of resistance arteries. In particular, angiotensin II AT1 receptors (AT1Rs) emerged as mechanosensors mediating myogenic tone. Moreover, we found that the AT1B receptor isoform was more mechanosensitive than the AT1A receptor. Interestingly, cysteinyl leukotriene 1 receptors (CysLT1Rs) were up‐regulated in AT1R‐deficient arteries as an essential backup strategy to compensate for the loss of vasoconstrictor receptors. Up‐regulation of CysLT1Rs resulted in increased myogenic tone at low intraluminal pressures resulting in hyperactivity of AT1R‐deficient arteries. Only at high intraluminal pressures myogenic tone was reduced, thus reflecting the loss of AT1Rs. Further, CysLT1Rs were involved in myogenic vasoconstriction of wild‐type arteries. Simultaneous blockade of AT1Rs and CysLT1Rs in wild‐type arteries caused reduction in myogenic tone of more than 60% comparable to the application of the selective Gq/11‐protein inhibitor YM‐254890. Our findings suggest that AT1Rs and CysLT1Rs are crucial mechanosensors in resistance arteries mediating 60% of myogenic vasoconstriction via the Gq/11‐protein pathway without involvement of endogenous agonists.
The complex task of measuring intestinal permeability in basic and clinical science
Authors: Galipeau H. J. , Verdu E. F. 
Published: June 2016

AbstractIntestinal permeability is a key feature of intestinal barrier function. Altered intestinal permeability is described in many chronic diseases and may be a risk factor for disease development and a target for emerging therapeutics. Thus, reliable and sensitive methods to measure intestinal permeability in both the clinical and preclinical setting are needed. There is currently a large array of tests to choose from, each with advantages and disadvantages. When possible, a combination of methods should be used. The choice of tests should be based on a deep understanding of intestinal barrier physiology and the recognition of their limitations. This mini‐review will highlight the advantages and limitations associated with intestinal permeability tests and will identify current problems in the field and how they can be addressed in the future.
Early Implantation of Primary Prevention Implantable Cardioverter Defibrillators for Patients with Newly Diagnosed Severe Nonischemic Cardiomyopathy
Authors: VOSKOBOINIK ALEKSANDR , BLOOM JASON , TAYLOR ANDREW , MARIANI JUSTIN 
Published: June 2016

BackgroundPrimary prevention implantable cardioverter defibrillators (ICDs) reduce mortality in selected patients with severe systolic dysfunction. Current guidelines suggest a 3‐ to 6‐month waiting period before implantation.MethodsWe retrospectively studied 29 consecutive patients with newly diagnosed nonischemic cardiomyopathy (NICM) who underwent primary prevention ICD implantation within 6 months of diagnosis between January 2008 and April 2014. Cardiac MRI (CMR) evaluated left ventricular ejection fraction (LVEF) and regional fibrosis preimplant. The primary end point was “failure to qualify for an ICD at 12 months postimplant,” either due to LVEF ≥ 35% or deterioration necessitating mechanical support or transplantation, without appropriate ICD therapy. Secondary end points were appropriate and inappropriate ICD therapy.ResultsBaseline mean age was 44.2 ± 14.8 years and median LVEF 16.4%. Median time from diagnosis to implant was 32 days. At 12 months, 17 patients (58.6%) no longer qualified for an ICD, mainly due to LVEF improvement. At follow‐up (mean 32.0 ± 20.6 months), three patients received appropriate therapy (one for ventricular fibrillation). All three had CMR late gadolinium enhancement (LGE) and nonsustained ventricular tachycardia (NSVT) preimplant. Cardiac resynchronization at implant predicted LVEF improvement.ConclusionEarly appropriate therapy, particularly for ventricular fibrillation, is infrequent for patients with very severe NICM who have ICDs implanted within 6 months of diagnosis. The majority of these patients would not qualify for an ICD at 12 months postinsertion. In the absence of a multimodality risk score, early ICD insertion should only be considered in selected cases (presence of LGE and NSVT). Wearable cardioverter defibrillators may have a role as a bridge to ICD decision.
The drought response of potato reference cultivars with contrasting tolerance
Authors: Sprenger Heike , Kurowsky Christina , Horn Renate , Erban Alexander , Seddig Sylvia , Rudack Katharina , Fischer Axel , Walther Dirk , Zuther Ellen , Köhl Karin , Hincha Dirk K. , Kopka Joachim 
Published: June 2016

AbstractSystems responses to drought stress of four potato reference cultivars with differential drought tolerance (Solanum tuberosumL.) were investigated by metabolome profiling and RNA sequencing. Systems analysis was based on independent field and greenhouse trials. Robust differential drought responses across all cultivars under both conditions comprised changes of proline, raffinose, galactinol, arabitol, arabinonic acid, chlorogenic acid and 102 transcript levels. The encoded genes contained a high proportion of heat shock proteins and proteins with signalling or regulatory functions, for example, a homolog of abscisic acid receptor PYL4. Constitutive differences of the tolerant compared with the sensitive cultivars included arbutin, octopamine, ribitol and 248 transcripts. The gene products of many of these transcripts were pathogen response related, such as receptor kinases, or regulatory proteins, for example, a homolog of theArabidopsisFOUR LIPS MYB‐regulator of stomatal cell proliferation. Functional enrichment analyses imply heat stress as a major acclimation component of potato leaves to long‐term drought stress. Enhanced heat stress during drought can be caused by loss of transpiration cooling. This effect and CO2limitation are the main consequences of drought‐induced or abscisic acid‐induced stomatal closure. Constitutive differences in metabolite and transcript levels between tolerant and sensitive cultivars indicate interactions of drought tolerance and pathogen resistance in potato.
Drought‐induced xylem pit membrane damage in aspen and balsam poplar
Authors: Hillabrand Rachel M. , Hacke Uwe G. , Lieffers Victor J. 
Published: June 2016

AbstractDrought induces an increase in a tree's vulnerability to a loss of its hydraulic conductivity in many tree species, including two common in western Canada, trembling aspen (Populus tremuloides) and balsam poplar (Populus balsamifera). Termed ‘cavitation fatigue’ or ‘air‐seeding fatigue’, the mechanism of this phenomenon is not well understood, but hypothesized to be a result of damage to xylem pit membranes. To examine the validity of this hypothesis, the effect of drought on the porosity of pit membranes in aspen and balsam poplar was investigated. Controlled drought and bench dehydration treatments were used to induce fatigue and scanning electron microscopy (SEM) was used to image pit membranes for relative porosity evaluations from air‐dried samples after ethanol dehydration. A significant increase in the diameter of the largest pore was found in the drought and dehydration treatments of aspen, while an increase in the percentage of porous pit membranes was found in the dehydration treatments of both species. Additionally, the location of the largest pore per pit membrane was observed to tend toward the periphery of the membrane.
Surface Arginine Saturation Effect on Unfolding Reaction of Firefly Luciferase: A Thermodynamic and Kinetic Perspective
Authors: Solgi Zahra , Khalifeh Khosrow , Hosseinkhani Saman , Ranjbar Bijan 
Published: June 2016

AbstractReplacement of some hydrophobic solvent‐exposed residues in Lampyris turkestanicus luciferase with arginine increases thermostability of this enzyme. Herein, thermodynamic and kinetic of unfolding reactions of wild type (WT), E354R/356R, E354R/356R‐I232R and E354R/356R‐Q35R/L182R/I232R variants, has been investigated. Fluorescence and Far‐UV circular dichroism measurements using urea as a chemical denaturant indicated that the value of for all variants is greater than that of WT enzyme. Analysis of m‐values, as a measure of difference in the solvent accessible surface area between the native and denatured states of protein, revealed that higher stability of mutants is related to their higher degree of compactness in the folded state. Results of unfolding kinetic experiments showed that all variants have three‐exponential behavior in which they unfolded with three rate constants and corresponding amplitudes. Increasing the rate constants of fast unfolding phase in mutants relative to WT protein may be attributed to more compactness and more kinetic sensitivity of their folded state to urea. However, more population of WT protein was unfolded from fast unfolding phase. Results of this investigation highlight kinetic stability of luciferase via a slow rate of unfolding.
Bridging the Gap between Evidence and Policy Makers: A Case Study of the Pew‐MacArthur Results First Initiative
Authors: VanLandingham Gary , Silloway Torey 
Published: June 2016

AbstractDeveloping ways to bridge the long‐recognized gap between researchers and policy makers is increasingly important in this age of constrained public resources. As noted by recent scholarship, progress toward evidence‐informed policy making requires both improving the supply of research that is reliable, timely, and relevant to the policy process and promoting demand and support for this information among decision makers. This article presents a case study of the Pew‐MacArthur Results First Initiative, which is working in a growing number of state and local governments to build systems that bring rigorous evidence on “what works” into their budget processes and to support its use in resource allocation decisions. The initiative's experience to date is promising, although creating lasting and dynamic evidence‐based policy‐making systems requires a long‐term commitment by both researchers and policy makers.
Beta‐lactam plus macrolides or beta‐lactam alone for community‐acquired pneumonia: A systematic review and meta‐analysis
Authors: Horita Nobuyuki , Otsuka Tatsuya , Haranaga Shusaku , Namkoong Ho , Miki Makoto , Miyashita Naoyuki , Higa Futoshi , Takahashi Hiroshi , Yoshida Masahiro , Kohno Shigeru , Kaneko Takeshi 
Published: June 2016

AbstractIt is unclear whether in the treatment of community‐acquired pneumonia (CAP) beta‐lactam plus macrolide antibiotics lead to better survival than beta‐lactam alone. We report a systematic review and meta‐analysis. Trials and observational studies published in English were included, if they provided sufficient data on odds ratio for all‐cause mortality for a beta‐lactam plus macrolide regimen compared with beta‐lactam alone. Two investigators independently searched for eligible articles. Of 514 articles screened, 14 were included: two open‐label randomized controlled trials (RCTs) comprising 1975 patients, one non‐RCT interventional study comprising 1011 patients and 11 observational studies comprising 33 332 patients. Random‐model meta‐analysis yielded an odds ratio for all‐cause death for beta‐lactam plus macrolide compared with beta‐lactam alone of 0.80 (95% CI 0.69–0.92, P = 0.002) with substantial heterogeneity (I2 = 59%, P for heterogeneity = 0.002). Severity‐based subgroup analysis and meta‐regression revealed that adding macrolide had a favourable effect on mortality only for severe CAP. Of the two RCTs, one suggested that macrolide plus beta‐lactam lead to better outcome compared with beta‐lactam alone, while the other did not. Subgrouping based on study design, that is, RCT versus non‐RCT, which was almost identical to subgrouping based on severity, revealed substantial inter‐subgroup heterogeneity. Compared with beta‐lactam alone, beta‐lactam plus macrolide may decrease all‐cause death only for severe CAP. However, this conclusion is tentative because this was based mainly on observational studies.
Prediction of Settlement Delay in Critical Illness Insurance Claims by Using the Generalized Beta of the Second Kind Distribution
Authors: Dodd Erengul , Streftaris George 
Published: June 2016

SummaryWe analyse the delay between diagnosis of illness and claim settlement in critical illness insurance by using generalized linear-type models under a generalized beta of the second kind family of distributions. A Bayesian approach is employed which allows us to incorporate parameter and model uncertainty and also to impute missing data in a natural manner. We propose methodology involving a latent likelihood ratio test to compare missing data models and a version of posterior predictive p-values to assess different models. Bayesian variable selection is also performed, supporting a small number of models with small Bayes factors, and therefore we base our predictions on model averaging instead of on a best-fitting model.
Factivity and Complement‐Types
Authors: Schueler David 
Published: June 2016

AbstractIn this paper I argue that the presuppositions associated with factive predicates are triggered not by the predicates themselves, but by their complement clauses. Evidence is brought to bear from different clause types in English, some of which, such as some gerunds and nominalizations, cause the presuppositions to disappear in certain uses of the implicit conditional, or simple subjunctive, construction. I survey the attempt to analyze these facts by assuming that factive predicates trigger presuppositions, that their complement clauses do, and that both do, and find that the thesis that solely the complement clauses are responsible for the presuppositions achieves the maximum explanatory power. This hypothesis has further implications for the nature of presuppositions in general.
Identification of a novel frequent RHCE*ce308T variant allele in Chinese D– individuals, resulting in a C+c– phenotype
Authors: Stegmann Tamara C. , Ji Yanli , Bijman Renate , Wang Zhen , Wen Jizhi , Wei Ling , Veldhuisen Barbera , Haer‐Wigman Lonneke , Lighthart Peter , Lodén‐van Straaten Martin , Luo Guangping , van der Schoot C. Ellen 
Published: June 2016

BACKGROUNDThe RHCE allele is highly polymorphic; more than 60 variants have been described leading to diminished expression of C, c, E, and e antigens. Not much is known about the prevalence of RHCE variants in the Chinese population. Individuals carrying a variant are at risk to develop alloantibodies in response to mismatched pregnancy or transfusion. In this study, phenotyping and genotyping of the RHCE allele in Chinese donors revealed a new clinically relevant mutation.STUDY DESIGN AND METHODSBlood samples from 200 D– and 200 D+ Chinese donors were analyzed by the RH multiplex ligation–dependent probe amplification (MLPA) assay and compared to serologically typed RhCE phenotypes, when available. All exons of the RHCE gene were sequenced in samples with aberrant genotyping results. The phenotype of the new variant RHCE allele was tested by transducing cultured human erythroblasts.RESULTSAberrant copy numbers for Exon 2 of the RHCE gene were discovered by MLPA in six D– donors (6/200), but not in D+ donors (0/200). Sequencing of the RHCE gene in these six donors identified a new variant RHCE*ce308C>T (p.103Pro>Leu) allele with an allele frequency of 0.015 within the D– individuals in this study. This variant was not detected in D+ individuals showing linkage with the D– haplotype. Serologically weak C expression and loss of c expression was demonstrated on donor red blood cells. In vitro transfection studies of the RHCE*ce308T variant in cDe/ce and CDe/CDe erythroblasts confirmed that the variant is associated with anti‐C reactivity while abolishing c expression.CONCLUSIONGenotyping of individuals carrying this variant by standard RHCE genotyping might falsely predict a C– phenotype or a c+ phenotype. This new variant should be taken into account in RHCE genotyping assays designed for the Chinese population.
Editing of the Bacillus subtilis Genome by the CRISPR-Cas9 System
Authors: Altenbuchner Josef 
Published: June 2016

ABSTRACT

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) systems are adaptive immune systems of bacteria. A type II CRISPR-Cas9 system from
Streptococcus pyogenes
has recently been developed into a genome engineering tool for prokaryotes and eukaryotes. Here, we present a single-plasmid system which allows efficient genome editing of
Bacillus subtilis
. The plasmid pJOE8999 is a shuttle vector that has a pUC minimal origin of replication for
Escherichia coli
, the temperature-sensitive replication origin of plasmid pE194
ts
for
B. subtilis
, and a kanamycin resistance gene working in both organisms. For genome editing, it carries the
cas9
gene under the control of the
B. subtilis
mannose-inducible promoter P

manP

and a single guide RNA (sgRNA)-encoding sequence transcribed via a strong promoter. This sgRNA guides the Cas9 nuclease to its target. The 20-nucleotide spacer sequence at the 5′ end of the sgRNA sequence, responsible for target specificity, is located between BsaI sites. Thus, the target specificity is altered by changing the spacer sequences via oligonucleotides fitted between the BsaI sites. Cas9 in complex with the sgRNA induces double-strand breaks (DSBs) at its target site. Repair of the DSBs and the required modification of the genome are achieved by adding homology templates, usually two PCR fragments obtained from both sides of the target sequence. Two adjacent SfiI sites enable the ordered integration of these homology templates into the vector. The function of the CRISPR-Cas9 vector was demonstrated by introducing two large deletions in the
B. subtilis
chromosome and by repair of the
trpC2
mutation of
B. subtilis
168.

IMPORTANCE
In prokaryotes, most methods used for scarless genome engineering are based on selection-counterselection systems. The disadvantages are often the lack of a suitable counterselection marker, the toxicity of the compounds needed for counterselection, and the requirement of certain mutations in the target strain. CRISPR-Cas systems were recently developed as important tools for genome editing. The single-plasmid system constructed for the genome editing of
B. subtilis
overcomes the problems of counterselection methods. It allows deletions and introduction of point mutations. It is easy to handle and very efficient, and it may be adapted for use in other firmicutes.