bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR/Cas9-Induced Disruption of Paraflagellar Rod Protein 1 and 2 Genes in Trypanosoma cruzi Reveals Their Role in Flagellar Attachment
Authors: Lander Noelia , Li Zhu-Hong , Niyogi Sayantanee , Docampo Roberto
Published: July 2015

Trypanosoma cruzi
is the etiologic agent of Chagas disease, and current methods for its genetic manipulation have been highly inefficient. We report here the use of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated gene 9) system for disrupting genes in the parasite by three different strategies. The utility of the method was established by silencing genes encoding the GP72 protein, which is required for flagellar attachment, and paraflagellar rod proteins 1 and 2 (PFR1, PFR2), key components of the parasite flagellum. We used either vectors containing single guide RNA (sgRNA) and Cas9, separately or together, or one vector containing sgRNA and Cas9 plus donor DNA for homologous recombination to rapidly generate mutant cell lines in which the
PFR1
,
PFR2
, and
GP72
genes have been disrupted. We demonstrate that genome editing of these endogenous genes in
T. cruzi
is successful without detectable toxicity of Cas9. Our results indicate that PFR1, PFR2, and GP72 contribute to flagellar attachment to the cell body and motility of the parasites. Therefore, CRISPR/Cas9 allows efficient gene disruption in an almost genetically intractable parasite and suggest that this method will improve the functional analyses of its genome.

IMPORTANCE
Trypanosoma cruzi
is the agent of Chagas disease, which affects millions of people worldwide. Vaccines to prevent this disease are not available, and drug treatments are not completely effective. The study of the biology of this parasite through genetic approaches will make possible the development of new preventive or treatment options. Previous attempts to use the CRISPR/Cas9 in
T. cruzi
found a detectable but low frequency of Cas9-facilitated homologous recombination and fluorescent marker swap between exogenous genes, while Cas9 was toxic to the cells. In this report, we describe new approaches that generate complete disruption of an endogenous gene without toxicity to the parasites and establish the relevance of several proteins for flagellar attachment and motility.
Maintaining sharp focus on a grainy film: miliary pattern in an elderly woman with acute respiratory failure
Authors: Hensley Patrick , Hilal Talal , Neltner Janna , Kumar Bharat
Published: July 2015

An elderly woman with a history of pulmonary tuberculosis reportedly diagnosed and treated 30 years prior to presentation was found unresponsive at home. Chest imaging revealed innumerable pulmonary nodules worrisome for an infectious process, specifically tuberculosis. The patient deteriorated rapidly and in accordance with her wishes, aggressive interventions were withheld. She died within 48 h from respiratory failure. A limited chest autopsy was performed and revealed the cause of death as lymphangitic spread of cancer from a primary lung adenocarcinoma.
Efficacy of rehabilitation (lengthening) exercises, platelet-rich plasma injections, and other conservative interventions in acute hamstring injuries: an updated systematic review and meta-analysis
Authors: Pas Haiko IMFL , Reurink Gustaaf , Tol Johannes L , Weir Adam , Winters Marinus , Moen Maarten H
Published: July 2015

Background

Our 2012 review on therapeutic interventions for acute hamstring injuries found a lack of high-quality studies. The publication of new studies warranted an update.

Objectives

To update and reanalyse the efficacy of conservative treatments for hamstring injury.

Data sources

PubMed, EMBASE, Web of Science, Cochrane library, CINAHL and SPORTDiscus were searched till mid-February 2015.

Study eligibility criteria

Randomised controlled trials (RCTs) on the effect of conservative interventions versus a control group or other intervention for hamstring injuries (HI) were included.

Data analysis

The search results were screened independently by two authors. Risk of bias assessment was performed using a modified Downs and Black scale with a maximum score of 28. Meta-analysis was performed, where possible.

Main results

10 RCTs (526 participants), including 6 new RCTs, were identified. Two RCTs were of good/excellent quality, the rest were fair or poor (median Downs and Black score 16 (IQR 9)). Meta-analysis of two studies on rehabilitation (lengthening) exercises showed a significantly reduced time to return to play (HR 3.22 (95% CI 2.17 to 4.77), p<0.0001) but no difference in risk of re-injury. Meta-analysis of three studies investigating platelet-rich plasma (PRP) showed no effect when compared to control (HR 1.03 (95% CI 0.87 to 1.22), p=0.73). Limited evidence was found that progressive agility and trunk stability training may reduce re-injury rates.

Conclusions

Meta-analysis showed superior efficacy for rehabilitation exercises. PRP injection had no effect on acute hamstring injury. Limited evidence was found that agility and trunk stabilisation may reduce re-injury rates. The limitations identified in the majority of RCTs should improve the design of new hamstring RCTs.
Is the introduction of violence and injury observatories associated with a reduction of violence in adult populations? Rationale and protocol for a systematic review
Authors: Jabar Ardil , Barth Dylan , Matzopoulos Richard , Engel Mark Emmanuel
Published: July 2015

Introduction

The violence and injury observatories developed in Colombia and found throughout the Americas and Western Europe aim to maximise inter-institutional cooperation, information-sharing, analysis and security policy development initiatives to enhance governance. The purpose of the violence and injury observatories is directed towards preventing crime and violence at the local and regional levels. To date, there has been no systematic review of the literature to present a succinct review of the evidence. We therefore sought to summarise the evidence from existing studies on the contribution of violence and injury observatories towards violence prevention.

Methods and analysis

A number of databases will be searched, supplemented by the same keyword searches in the grey literature. Search terms will include studies published from 1 January 1990 to 30 October 2014. Study quality will be assessed using a validated quality assessment tool. Two researchers will independently assess articles for study eligibility to reduce bias, minimise errors and enhance the reliability of findings. Disagreements will be resolved by consensus among three authors. This review protocol has been published in the PROSPERO International Prospective Register of systematic reviews, registration number 2014:CRD42014009818.

Dissemination

There is a paucity of evidence for the effectiveness of violence and injury observatories and their influence on violence in an adult population. We plan to address this gap in knowledge by way of a systematic review and meta-analysis outlined in this abstract. We anticipate that the results could be used by researchers and policymakers to help inform them of the efficacy of violence and injury observatories and their broader role in contributing to violence prevention.

Trial registration number

CRD42014009818.
Safety in numbers: more walkers and bicyclists, safer walking and bicycling
Authors: Jacobsen P L
Published: July 2015

Objective

To examine the relationship between the numbers of people walking or bicycling and the frequency of collisions between motorists and walkers or bicyclists. The common wisdom holds that the number of collisions varies directly with the amount of walking and bicycling. However, three published analyses of collision rates at specific intersections found a non-linear relationship, such that collisions rates declined with increases in the numbers of people walking or bicycling.

Data

This paper uses five additional data sets (three population level and two time series) to compare the amount of walking or bicycling and the injuries incurring in collisions with motor vehicles.

Results

The likelihood that a given person walking or bicycling will be struck by a motorist varies inversely with the amount of walking or bicycling. This pattern is consistent across communities of varying size, from specific intersections to cities and countries, and across time periods.

Discussion

This result is unexpected. Since it is unlikely that the people walking and bicycling become more cautious if their numbers are larger, it indicates that the behavior of motorists controls the likelihood of collisions with people walking and bicycling. It appears that motorists adjust their behavior in the presence of people walking and bicycling. There is an urgent need for further exploration of the human factors controlling motorist behavior in the presence of people walking and bicycling.

Conclusion

A motorist is less likely to collide with a person walking and bicycling if more people walk or bicycle. Policies that increase the numbers of people walking and bicycling appear to be an effective route to improving the safety of people walking and bicycling.
Clinical reasoning in canine spinal disease: what combination of clinical information is useful?
Authors: Cardy T. J. A. , De Decker S. , Kenny P. J. , Volk H. A.
Published: July 2015

Spinal disease in dogs is commonly encountered in veterinary practice. Numerous diseases may cause similar clinical signs and presenting histories. The study objective was to use statistical models to identify combinations of discrete parameters from the patient signalment, history and neurological examination that could suggest the most likely diagnoses with statistical significance. A retrospective study of 500 dogs referred to the Queen Mother Hospital for Animals before June 2012 for the investigation of spinal disease was performed. Details regarding signalment, history, physical and neurological examinations, neuroanatomical localisation and imaging data were obtained. Univariate analyses of variables (breed, age, weight, onset, deterioration, pain, asymmetry, neuroanatomical localisation) were performed, and variables were retained in a multivariate logistic regression model if P<0.05. Leading diagnoses were intervertebral disc extrusion (IVDE, n=149), intervertebral disc protrusion (n=149), ischaemic myelopathy (IM, n=48) and neoplasms (n=44). Multivariate logistic regression characterised IM and acute non‐compressive nucleus pulposus extrusions as the only peracute onset, non‐progressive, non‐painful and asymmetrical T3‐L3 myelopathies. IVDE was most commonly characterised as acute onset, often deteriorating, painful and largely symmetrical T3‐L3 myelopathy. This study suggests that most spinal diseases cause distinctive combinations of presenting clinical parameters (signalment, onset, deterioration, pain, asymmetry, neuroanatomical localisation). Taking particular account of these parameters may aid decision making in a clinical setting.
A comparison of the early developmental morphologies ofAponogeton madagascariensisandA.boivinianus
Authors: Dauphinee Adrian N. , Lacroix Christian R. , Gunawardena Arunika H.L.A.N.
Published: July 2015

Aponogeton madagascariensis (Mirb.) H. Bruggen is an aquatic monocot that develops perforations in its leaves through developmentally regulated programmed cell death (PCD). Aponogeton boivinianus Baill. ex Jum. is a close relative found in comparable environments with leaves that have a similar shape with no perforations. Little is known about the early developmental morphology of the family. This study characterized and compared these two species via scanning electron microscopy (SEM) and confocal laser scanning microscopy using both fresh and fixed specimens. The shoot apical meristem (SAM) of A. madagascariensis was significantly larger than that of A. boivinianus, but there was no difference in phyllotaxy observed, as both exhibited a 2/5 spiral pattern. A novel technique using serial dissections and SEM of fresh, hydrated specimens revealed that there are 16 plastochrons before perforation formation in A. madagascariensis and 34 plastochrons until a similar developmental stage in A. boivinianus. The effects on early development of A. madagascariensis plants with supressed ethylene production were also analyzed. Ethylene inhibition alters leaf development by blocking PCD, but had no significant effect on the SAM morphology or early leaf development in A. madagascariensis.
DFT investigation on interaction of chlorine with In2O3 nanostructures
Authors: Nagarajan V. , Chandiramouli R.
Published: July 2015

The structural, electronic, and adsorption properties of chlorine on pristine, tin-, aluminum-, and fluorine-substituted In2O3 nanostructures are successfully optimized and computed using density functional theory along with the B2LYP/LanL2DZ basis set. The electronic properties of pristine, tin-, aluminum-, and fluorine-substituted In2O3 nanostructures are discussed in terms of ionization potential, HOMO–LUMO gap, and electron affinity. The dipole moment and point symmetry group of In2O3 nanostructures are also reported. The structural stability of pristine, tin-, aluminum-, and fluorine-substituted In2O3 nanostructures are investigated in terms of formation energy. The adsorption properties of chlorine on In2O3 are studied and the most appropriate adsorption sites of Cl2 on In2O3 nanostructures are reported. The adsorption properties of hydrogen on In2O3 nanostructures are also investigated and inferred that In2O3 exhibits good sensing characteristics towards hydrogen. The adsorbed energy, HOMO–LUMO gap, Mulliken population analysis, and average energy gap variation are used to identify the prominent adsorption site of Cl2 on In2O3 material. The substitution of fluorine in In2O3 nanostructures enhances the Cl2 adsorption properties in the mixed gas atmosphere.
A 24-h design storm for the Fort McMurray region
Authors: Dick Wes , Ghavasieh Ahmadreza
Published: July 2015

The time distribution of rainfall is an important input to rainfall-runoff modelling and has a significant effect on the resulting peak discharge. At many facilities in the oil sands region of Alberta, the Natural Resources Conservation Service (NRCS) Type II design storm has typically been used for design of surface water management facilities. The appropriateness of the Type II design storm and several other time distributions was assessed by comparing the modelled peak runoff from the design storms with the modelled runoff from historical 24-h rainfall events in five small typical catchments. Results indicate that the NRCS Type II produces highly conservative runoff peaks compared to actual rainfall events at Fort McMurray, and a new synthetic design storm developed during the study more closely parallels the peak runoff produced by actual rainfall events.
Mode of action of metabolites fromBacillussp. strain IBA 33 onGeotrichum citri-aurantiiarthroconidia
Authors: Gordillo María Antonieta , Navarro Antonio R. , Maldonado María Cristina
Published: July 2015

Geotrichum citri-aurantii is a postharvest phytopathogenic fungus of lemons. We studied the mode of action of antifungal metabolites from Bacillus sp. strain IBA 33 on arthroconidia of G. citri-aurantii. These metabolites are lipopeptides belonging to the iturin family. Membrane permeabilization of G. citri-aurantii was analyzed and mitochondrial respiratory rate was evaluated. Disturbance of the plasma membrane promotes the leakage of many cellular components into the surrounding media, and mitochondrial membrane disorganization promotes the inhibition of the respiratory rate. Our findings provide insights into the ability of lipopeptides to suppress plant fungal pathogens and their possible agronomical applications.
Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies
Authors: Abdel-Daim Mohamed M. , Taha Ramadan , Ghazy Emad W. , El-Sayed Yasser S.
Published: July 2015

Diazinon (DZN) is a common organophosphorus insecticide extensively used for agriculture and veterinary purposes. DZN toxicity is not limited to insects; it also induces harmful effects in mammals and birds. Our experiment evaluated the protective and antioxidant potential of sesame oil (SO) and (or) alpha-lipoic acid (ALA) against DZN toxicity in male Wistar albino rats. DZN-treated animals exhibited macrocytic hypochromic anemia and significant increases in serum biochemical parameters related to liver injury, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γGT), cholesterol, and triglycerides. They also had elevated levels of markers related to cardiac injury, such as lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and increased biomarkers of renal injury, urea and creatinine. DZN also increased hepatic, renal, and cardiac lipid peroxidation and decreased antioxidant biomarker levels. SO and (or) ALA supplementation ameliorated the deleterious effects of DZN intoxication. Treatment improved hematology and serum parameters, enhanced endogenous antioxidant status, and reduced lipid peroxidation. Importantly, they exerted synergistic hepatoprotective, nephroprotective, and cardioprotective effects. Our findings demonstrate that SO and (or) ALA supplementation can alleviate the toxic effects of DZN via their potent antioxidant and free radical-scavenging activities.
Arterial stiffness evaluated by cardio-ankle vascular index (CAVI) in adolescent hypertension
Authors: Mestanik Michal , Jurko Alexander , Mestanikova Andrea , Jurko Tomas , Tonhajzerova Ingrid
Published: July 2015

Elevated blood pressure (BP) is a major risk factor for atherosclerosis. As the studies concerning vascular alterations in pediatric patients are rare, we aimed to study the relationship between hypertension and arterial stiffness in adolescence by novel method independent from BP during examination. Twenty nonobese adolescent boys (16.5 ± 0.4 years) with newly diagnosed essential hypertension, 20 adolescent boys (16.7 ± 0.4 years) with newly diagnosed white-coat hypertension, and 20 healthy controls matched to age and body mass index were examined. Cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), pre-ejection period (PEP), and ejection time (ET) were evaluated. CAVI was significantly increased in essential hypertension patients compared with controls (p < 0.05) with no significant difference in white-coat hypertension patients. Significantly higher baPWV was found in essential and white-coat hypertension patients compared with controls (both p < 0.001). White-coat hypertension patients showed significantly shortened PEP and ET compared with controls (p < 0.01 and p < 0.001, respectively) and essential hypertension patients (both p < 0.05). For the first time, the arterial stiffness in adolescents with newly diagnosed essential and white-coat hypertension was studied using BP-independent index CAVI combined with conventional baPWV. Our study revealed significantly increased CAVI in adolescents with newly diagnosed essential hypertension compared with controls. Our findings could help to understand hypertension–atherosclerosis interaction.
ADDING A BASIC PILLAR TO THE CENTRAL PROVIDENT FUND SYSTEM: AN ACTUARIAL ANALYSIS
Authors: CHIA NGEE-CHOON
Published: July 2015

The Central Provident Fund (CPF) system has worked well for majority of Singaporeans who are able to work consistently over their life cycle and have made prudent housing choices. However, the inherent structure of CPF, which is based purely on contributions, is unable to address retirement adequacy for its vulnerable members. Adding a means-tested non-contributory basic pillar to the system will make the system more inclusive. This paper studies the pension cost of a targeted old-age income support system for needy elderly to help meet their basic living expenses. A Lee–Carter stochastic model is used to forecast the elderly population. Pension costs depend on coverage and benefit levels and the cost of living adjustments. The viability of a basic retirement support scheme would also depend on the speed of ageing and the rate of economic growth.
Cyclic entropy: An alternative to inflationary cosmology
Authors: Frampton Paul Howard
Published: July 2015

We address how to construct an infinitely cyclic universe model. A major consideration is to make the entropy cyclic which requires the entropy to be reset to zero in each cycle expansion [Formula: see text] turnaround [Formula: see text] contraction [Formula: see text] bounce [Formula: see text] etc. Here, we reset entropy at the turnaround by selecting the introverse (visible universe) from the extroverse which is generated by the accelerated expansion. In the model, the observed homogeneity is explained by the low entropy at the bounce. The observed flatness arises from the contraction together with the reduction in size between the expanding and contracting universe. The present flatness is predicted to be very precise.
Diphoton decay of the Higgs boson and new bound states of top and antitop quarks
Authors: Froggatt C. D. , Das C. R. , Laperashvili L. V. , Nielsen H. B.
Published: July 2015

We consider the constraints, provided by the LHC results on Higgs boson decay into 2 photons and its production via gluon fusion, on the previously proposed Standard Model (SM) strongly bound state S of six top quarks and six antitop quarks. A correlation is predicted between the ratios [Formula: see text] and [Formula: see text] of the Higgs diphoton decay and gluon production amplitudes, respectively to their SM values. We estimate the contribution to these amplitudes from one-loop diagrams involving the 12 quark bound state S and related excited states using an atomic physics based model. We find two regions of parameter space consistent with the ATLAS and CMS data on [Formula: see text] at the three sigma level: a region close to the SM values [Formula: see text] with the mass of the bound state [Formula: see text][Formula: see text]GeV and a region with [Formula: see text] corresponding to a bound state mass of [Formula: see text][Formula: see text]GeV.
Crystallographic effects during micromachining — A finite-element model
Authors: Song Shin-Hyung , Choi Woo Chun
Published: July 2015

Mechanical micromachining is a powerful and effective way for manufacturing small sized machine parts. Even though the micromachining process is similar to the traditional machining, the material behavior during the process is much different. In particular, many researchers report that the basic mechanics of the work material is affected by microstructures and their crystallographic orientations. For example, crystallographic orientations of the work material have significant influence on force response, chip formation and surface finish. In order to thoroughly understand the effect of crystallographic orientations on the micromachining process, finite-element model (FEM) simulating orthogonal cutting process of single crystallographic material was presented. For modeling the work material, rate sensitive single crystal plasticity of face-centered cubic (FCC) crystal was implemented. For the chip formation during the simulation, element deletion technique was used. The simulation model is developed using ABAQUS/explicit with user material subroutine via user material subroutine (VUMAT). Simulations showed that variation of the specific cutting energy at different crystallographic orientations of work material shows significant anisotropy. The developed FEM model can be a useful prediction tool of micromachining of crystalline materials.
New Bondi-type outgoing boundary condition for the Einstein equations with cosmological constant
Authors: He Xiaokai , Cao Zhoujian
Published: July 2015

In the middle of last century, Bondi and his coworkers proposed an outgoing boundary condition for the Einstein equations. Recently, more and more observations imply that the Einstein equations should include a nonzero cosmological constant. A spacetime with a positive cosmological constant approaches to a de Sitter space asymptotically. Bondi's original boundary condition is not valid for these asymptotically de Sitter spacetimes. But the traditional conformally flat boundary condition excludes the gravitational radiation for the asymptotically de Sitter spacetimes. In this work, a new Bondi-type outgoing boundary condition based on Bondi–Sachs coordinates is considered. With this new boundary condition, the gravitational wave behavior for the asymptotically de Sitter spacetime is similar to the one for the asymptotically Minkowski spacetime. The traditional conformally flat boundary condition falls into a special subclass of the new boundary condition.
Synthesis of Magnetic/Graphene Oxide Composite and Application for High-Performance Removal of Polycyclic Aromatic Hydrocarbons from Contaminated Water
Authors: Zhong Yaping , Wang Shan , He Yu , Song Gongwu
Published: July 2015

An effective method for rapid and high efficiency removal of Polycyclic aromatic hydrocarbons from contaminated water had been proposed based on the Graphene/silica magnetic nanocomposites (M/GO). Factors affecting the adsorption efficiency of M/GO were investigated and we found that the optimum adsorption pH was 5.5, adsorption time was 20 min and adsorbent concentration was 400 mg⋅L-1 for phenanthrene and 1200 mg⋅L-1 for pyrene, respectively. The adsorption mechanisms were also discussed. The regeneration and reuse experiments showed good reusability of the as-prepared adsorbent. In addition, this method was successfully applied to the rapid and high efficiency removal of phenanthrene and pyrene from real water samples, which presages more opportunities for application in environment and material sciences.
Algorithms for Mining the Coevolving Relational Motifs in Dynamic Networks
Authors: Ahmed Rezwan , Karypis George
Published: July 2015

Computational methods and tools that can efficiently and effectively analyze the temporal changes in dynamic complex relational networks enable us to gain significant insights regarding the entity relations and their evolution. This article introduces a new class of dynamic graph patterns, referred to as coevolving relational motifs (CRMs), which are designed to identify recurring sets of entities whose relations change in a consistent way over time. CRMs can provide evidence to the existence of, possibly unknown, coordination mechanisms by identifying the relational motifs that evolve in a similar and highly conserved fashion. We developed an algorithm to efficiently analyze the frequent relational changes between the entities of the dynamic networks and capture all frequent coevolutions as CRMs. Our algorithm follows a depth-first exploration of the frequent CRM lattice and incorporates canonical labeling for redundancy elimination. Experimental results based on multiple real world dynamic networks show that the method is able to efficiently identify CRMs. In addition, a qualitative analysis of the results shows that the discovered patterns can be used as features to characterize the dynamic network.
Perceptual Tolerance to Stereoscopic 3D Image Distortion
Authors: Allison Robert S. , Wilcox Laurie M.
Published: July 2015

An intriguing aspect of picture perception is the viewer’s tolerance to variation in viewing position, perspective, and display size. These factors are also present in stereoscopic media, where there are additional parameters associated with the camera arrangement (e.g., separation, orientation). The predicted amount of depth from disparity can be obtained trigonometrically; however, perceived depth in complex scenes often differs from geometric predictions based on binocular disparity alone. To evaluate the extent and the cause of deviations from geometric predictions of depth from disparity in naturalistic scenes, we recorded stereoscopic footage of an indoor scene with a range of camera separations (camera interaxial (IA) ranged from 3 to 95 mm) and displayed them on a range of screen sizes. In a series of experiments participants estimated 3D distances in the scene relative to a reference scene, compared depth between shots with different parameters, or reproduced the depth between pairs of objects in the scene using reaching or blind walking. The effects of IA and screen size were consistently and markedly smaller than predicted from the binocular viewing geometry, suggesting that observers are able to compensate for the predicted distortions. We conclude that the presence of multiple realistic monocular depth cues drives normalization of perceived depth from binocular disparity. It is not clear to what extent these differences are due to cognitive as opposed to perceptual factors. However, it is notable that these normalization processes are not task specific; they are evident in both perception- and action-oriented tasks.
A Survey of CPU-GPU Heterogeneous Computing Techniques
Authors: Mittal Sparsh , Vetter Jeffrey S.
Published: July 2015

As both CPUs and GPUs become employed in a wide range of applications, it has been acknowledged that both of these Processing Units (PUs) have their unique features and strengths and hence, CPU-GPU collaboration is inevitable to achieve high-performance computing. This has motivated a significant amount of research on heterogeneous computing techniques, along with the design of CPU-GPU fused chips and petascale heterogeneous supercomputers. In this article, we survey Heterogeneous Computing Techniques (HCTs) such as workload partitioning that enable utilizing both CPUs and GPUs to improve performance and/or energy efficiency. We review heterogeneous computing approaches at runtime, algorithm, programming, compiler, and application levels. Further, we review both discrete and fused CPU-GPU systems and discuss benchmark suites designed for evaluating Heterogeneous Computing Systems (HCSs). We believe that this article will provide insights into the workings and scope of applications of HCTs to researchers and motivate them to further harness the computational powers of CPUs and GPUs to achieve the goal of exascale performance.
An integrative role for the superior colliculus in selecting targets for movements
Authors: Wolf Andrew B. , Lintz Mario J. , Costabile Jamie D. , Thompson John A. , Stubblefield Elizabeth A. , Felsen Gidon
Published: July 2015

A fundamental goal of systems neuroscience is to understand the neural mechanisms underlying decision making. The midbrain superior colliculus (SC) is known to be central to the selection of one among many potential spatial targets for movements, which represents an important form of decision making that is tractable to rigorous experimental investigation. In this review, we first discuss data from mammalian models—including primates, cats, and rodents—that inform our understanding of how neural activity in the SC underlies the selection of targets for movements. We then examine the anatomy and physiology of inputs to the SC from three key regions that are themselves implicated in motor decisions—the basal ganglia, parabrachial region, and neocortex—and discuss how they may influence SC activity related to target selection. Finally, we discuss the potential for methodological advances to further our understanding of the neural bases of target selection. Our overarching goal is to synthesize what is known about how the SC and its inputs act together to mediate the selection of targets for movements, to highlight open questions about this process, and to spur future studies addressing these questions.
Noradrenergic refinement of glutamatergic neuronal circuits in the lateral superior olivary nucleus before hearing onset
Authors: Hirao Kenzo , Eto Kei , Nakahata Yoshihisa , Ishibashi Hitoshi , Nagai Taku , Nabekura Junichi
Published: July 2015

Neuronal circuit plasticity during development is fundamental for precise network formation. Pioneering studies of the developmental visual cortex indicated that noradrenaline (NA) is crucial for ocular dominance plasticity during the critical period in the visual cortex. Recent research demonstrated tonotopic map formation by NA during the critical period in the auditory system, indicating that NA also contributes to synaptic plasticity in this system. The lateral superior olive (LSO) in the auditory system receives glutamatergic input from the ventral cochlear nucleus (VCN) and undergoes circuit remodeling during postnatal development. LSO is innervated by noradrenergic afferents and is therefore a suitable model to study the function of NA in refinement of neuronal circuits. Chemical lesions of the noradrenergic system and chronic inhibition of α2-adrenoceptors in vivo during postnatal development in mice disrupted functional elimination and strengthening of VCN-LSO afferents. This was potentially mediated by activation of presynaptic α2-adrenoceptors and inhibition of glutamate release because NA presynaptically suppressed excitatory postsynaptic current (EPSC) through α2-adrenoceptors during the first two postnatal weeks in an in vitro study. Furthermore, NA and α2-adrenoceptor agonist induced long-term suppression of EPSCs and decreased glutamate release. These results suggest that NA has a critical role in synaptic refinement of the VCN-LSO glutamatergic pathway through failure of synaptic transmission. Because of the ubiquitous distribution of NA afferents and the extensive expression of α2-adrenoceptors throughout the immature brain, this phenomenon might be widespread in the developing central nervous system.
High-fat diet caused widespread epigenomic differences on hepatic methylome in rat
Authors: Zhang Yukun , Wang Huan , Zhou Dan , Moody Laura , Lezmi Stéphane , Chen Hong , Pan Yuan-Xiang
Published: July 2015

A high-fat (HF) diet is associated with progression of liver diseases. To illustrate genome-wide landscape of DNA methylation in liver of rats fed either a control or HF diet, two enrichment-based methods, namely methyl-DNA immunoprecipitation assay with high-throughput sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq), were performed in our study. Rats fed with the HF diet exhibited an increased body weight and liver fat accumulation compared with that of the control group when they were 12 wk of age. Genome-wide analysis of differentially methylated regions (DMRs) showed that 12,494 DMRs induced by HF diet were hypomethylated and 6,404 were hypermethylated. DMRs with gene annotations [differentially methylated genes (DMGs)] were further analyzed to show gene-specific methylation profile. There were 88, 2,680, and 95 hypomethylated DMGs identified with changes in DNA methylation in the promoter, intragenic and downstream regions, respectively, compared with fewer hypermethylated DMGs (45, 1,623, and 50 in the respective regions). Some of these genes also contained an ACGT cis-acting motif whose DNA methylation status may affect gene expression. Pathway analysis showed that these DMGs were involved in critical hepatic signaling networks related to hepatic development. Therefore, HF diet had global impacts on DNA methylation profile in the liver of rats, leading to differential expression of genes in hepatic pathways that may involve in functional changes in liver development.
Alveolar Rhabdomyosarcoma in a 69-Year-Old Woman Receiving Glucagon-Like Peptide-2 Therapy
Authors: Zyczynski Laura E. , McHugh Jonathan B. , Gribbin Thomas E. , Schuetze Scott M.
Published: July 2015

A 69-year-old woman was diagnosed with alveolar rhabdomyosarcoma (ARMS) of the nasopharynx. She has a history of catastrophic thromboembolic event in the abdomen that caused short-gut syndrome and dependence on total parenteral nutrition (TPN) twelve hours per day. She was treated for short-gut syndrome with teduglutide, a glucagon-like peptide-2 (GLP-2) analog, which led to reduction of TPN requirements. However, a few months later, she developed metastatic alveolar rhabdomyosarcoma. Though a causative relationship is unlikely between the peptide and ARMS due to the brief time course between teduglutide therapy and sarcoma diagnosis, neoplastic growth may have been accelerated by the GLP-2 analog, causing release of IGF-1. The transmembrane receptor for IGF-1 is frequently overexpressed in ARMS and is implicated in cell proliferation and metastatic behavior. This case describes a rare incidence of metastatic alveolar rhabdomyosarcoma in a sexagenarian and possibly the first case reported associated with the use of teduglutide. Teduglutide was discontinued due to a potential theoretical risk of acceleration of sarcoma growth, and the patient’s rhabdomyosarcoma is in remission following sarcoma chemotherapy.
A New Era of Laparoscopic Revision of Kasai Portoenterostomy for the Treatment of Biliary Atresia
Authors: Murase Naruhiko , Uchida Hiroo , Ono Yasuyuki , Tainaka Takahisa , Yokota Kazuki , Tanano Akihide , Shirota Chiyoe , Shirotsuki Ryo
Published: July 2015

Purpose.Kasai portoenterostomy is the standard therapy for biliary atresia (BA). If Kasai is unsuccessful, there is controversy over whether revision of Kasai restores adequate biliary drainage. Although there are several reports of laparoscopic Kasai (Lap-Kasai), none has described laparoscopic revision (Lap-revision). The purposes of this study were to evaluate the feasibility and efficacy of Lap-revision.Methods.65 patients underwent open Kasai between November 2001 and November 2013, and 12 patients underwent Lap-Kasai between December 2013 to January 2015. The indications for revision included bile flow cessation and recurrent cholangitis. Clinical data were compared between open and laparoscopic revisions of Kasai.Results.Open revision of Kasai was performed in 20 patients after open Kasai, and Lap-revision was performed in 4 patients after Lap-Kasai. Lap-revision was completed without conversion or major complication in any patient. The bilirubin level was normalized by Lap-revision in all four patients, and three of them were alive with their native liver. Open and laparoscopic revisions of Kasai were comparable in terms of the operation time, blood loss, and surgical outcomes.Conclusion.Lap-revision is a feasible and effective method for the treatment of BA and might herald a new era for the treatment of this disease.
Genetics of Human and Canine Dilated Cardiomyopathy
Authors: Simpson Siobhan , Edwards Jennifer , Ferguson-Mignan Thomas F. N. , Cobb Malcolm , Mongan Nigel P. , Rutland Catrin S.
Published: July 2015

Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.
Embolic Stroke as the Initial Manifestation of Systemic Lupus Erythematosus
Authors: Khan Reshma M. , Namas Rajaie , Parikh Sachin , Rubin Bernard
Published: July 2015

We present a case of a 21-year-old African-American female with no significant medical history, who presented to the emergency department with a one-week history of blurry and double vision. Ophthalmology evaluation revealed bilateral retinal artery occlusion. Further workup with imaging of the brain was consistent with an ischemic stroke. Hereditary hypercoagulable workup was unremarkable and initial testing for antiphospholipid syndrome was positive. She underwent transesophageal echocardiogram (TEE), which showed severe mitral regurgitation and thickening of mitral valve leaflets consistent with Libman-Sacks endocarditis. Autoimmune workup was positive for IF-ANA, anti-RNP, and anti-Smith antibody. She fulfilled 4/11 of the ACR criteria and met 5 of the SLICC (Systemic Lupus International Collaborating Clinics) criteria for lupus (nonscaring alopecia, thrombocytopenia, positive ANA, and positive anti-Smith and positive anti-phospholipid antibodies). This case highlights the importance of early recognition of underlying connective tissue diseases and timely management of these diseases in young patients with no previous manifestations of diseases.
Severity of Burn Injury and the Relationship to Socioeconomic Status in Nova Scotia, Canada
Authors: Le Jeffrey , Alyouha Sarah , Liu Lihui , Bezuhly Michael , Williams Jason
Published: July 2015

Objective. Few Canadian studies have examined the relationship between socioeconomic status (SES) and incidence of burn injury. We seek to evaluate this relationship using median income as a measure of SES in Nova Scotia, Canada.Methods. Nova Scotia residents admitted to the Queen Elizabeth II burn unit in Halifax, Nova Scotia, from 1995 to 2012, were included in the study. SES was estimated by linking the subject’s postal code to median family household income via Canadian population census data at the level of dissemination areas. Four equal income groups ranging from lowest to highest income quartile were compared (average total burn percentage). Likelihood ratio was calculated to evaluate the effect of median family income burn injury in each income quartile.Results. 302 patients were included in the analysis. Average percent total burn surface area was 19%, 15%, 15%, and 14% (p=0.18) per income quartile (Q1: lowest, Q4: highest), respectively. Likelihood ratios for income quartile Q1–Q4 were 1.3 (0.8–1.6), 1.2 (0.6–1.4), and 0.7 (0.6–1.2), respectively.Conclusion. Contrary to findings in other geographic regions of the world, severity or incidence of burn injury in Nova Scotia, Canada, does not change in relation to SES when using family median income as a surrogate.
Pulmonary Limited MPO-ANCA Microscopic Polyangiitis and Idiopathic Lung Fibrosis in a Patient with a Diagnosis of IgA Nephropathy
Authors: Tilanus Alwin , Van der Niepen Patricia , Geers Caroline , Wissing Karl Martin
Published: July 2015

We present a case of a male patient with chronic renal insufficiency, due to crescentic glomerulonephritis with IgA deposits, who successively developed (idiopathic) thrombocytopenic purpura (ITP) and MPO-ANCA microscopic polyangiitis (MPA) with pulmonary fibrosis. The patient presented with cough, weight loss, and dyspnea on exertion. CT imaging and pulmonary function tests were compatible with interstitial pneumonitis with pulmonary fibrosis. Laboratory results showed high MPO-ANCA titers; the urinary sediment was bland. The patient was treated successfully with cyclophosphamide and methyl-prednisolone. This unique case illustrates the diagnostic and therapeutic challenges of an unusual presentation of microscopic polyangiitis presenting first as isolated kidney disease with recurrence in the form of pneumonitis without renal involvement, in association with renal IgA deposits and ITP as coexisting autoimmune conditions.
Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study
Authors: Brouillette Ashley M. , Öz Gülin , Gomez Christopher M.
Published: July 2015

Neurodegenerative diseases, including the spinocerebellar ataxias (SCA), would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF) level of tau,α-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP), proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C), compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA). Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found thatα-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C.
Approximate Design of Optimal Disturbance Rejection for Discrete-Time Systems with Multiple Delayed Inputs: Application to a Jacket-Type Offshore Structure
Authors: Han Shi-Yuan , Wang Dong , Chen Yue-Hui , Tang Gong-You , Yang Xi-Xin
Published: July 2015

The study is concerned with problem of optimal disturbance rejection for a class of discrete-time systems with multiple delayed inputs. In order to avoid the two-point boundary value (TPBV) problem with items of time-delay and time-advance caused by multiple delayed inputs, the discrete-time system with multiple delayed inputs is transformed into a delay-free system by introducing a variable transformation, and the original performance index is reformulated as a corresponding form without the explicit appearance of time-delay items. Then, the approximate optimal disturbance rejection controller (AODRC) is derived from Riccati equation and Stein equation based on the reduced system and reformulated performance index, which is combined with feedback item of system state, feedforward item of disturbances, and items of delayed inputs. Also, the existence and uniqueness of AODRC are proved, and the stability of the closed-loop system is analysed. Finally, numerical examples of disturbance rejection for jacket-type offshore structure and pure mathematical model are illustrated to validate the feasibility and effectiveness of the proposed approach.
Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β
Authors: Zhou Mingjie , Ren Huanhuan , Han Jichun , Wang Wenjuan , Zheng Qiusheng , Wang Dong
Published: July 2015

Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats.Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β(GSK-3β), phospho-GSK-3β(P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis.Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and±dp/dtmax, as well as increased the levels of SOD and P-GSK-3βand GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α.Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3βactivity in rats with I/R.