bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational fluid dynamics in congenital heart disease
Authors: DeCampli William M. , Argueta-Morales I. Ricardo , Divo Eduardo , Kassab Alain J.
Published: January 2013

Computational fluid dynamics has been applied to the design, refinement, and assessment of surgical procedures and medical devices. This tool calculates flow patterns and pressure changes within a virtual model of the cardiovascular system. In the field of paediatric cardiac surgery, computational fluid dynamics is being used to elucidate the optimal approach to staged reconstruction of specific defects and study the haemodynamics of the resulting anatomical configurations after reconstructive or palliative surgery. In this paper, we review the techniques and principal findings of computational fluid dynamics studies as applied to a few representative forms of congenital heart disease.
Introduction: a lifelong interdisciplinary approach to common arterial trunk, transposition of the great arteries, and other evolving challenges in paediatric and congenital cardiac disease
Authors: Jacobs Jeffrey P.
Published: January 2013

This December Issue of Cardiology in the Young represents the tenth annual publication generated from the two meetings that compose “HeartWeek in Florida”. “HeartWeek in Florida”, the joint collaborative project sponsored by the Cardiac Center at the Children's Hospital of Philadelphia, together with All Children's Hospital of Saint Petersburg and Johns Hopkins Medicine, averages over 1000 attendees every year and is now recognized as one of the major planks of continuing medical and nursing education for those working in the fields of diagnosis and treatment of cardiac disease in the fetus, neonate, infant, child, and adult. “HeartWeek in Florida” combines the International Symposium on Congenital Heart Disease, organised by All Children's Hospital and Johns Hopkins Medicine and entering its 13th year, with the Annual Postgraduate Course in Pediatric Cardiovascular Disease, organised by The Children's Hospital of Philadelphia and entering its 17th year. The theme of this supplement generated from the 2012 HeartWeek in Florida is “A Lifelong Interdisciplinary Approach to Common Arterial Trunk, Transposition of the Great Arteries, and Other Evolving Challenges in Paediatric and Congenital Cardiac Disease”. We would like to acknowledge the tremendous contributions made to medicine by Richard Jonas; and therefore, we dedicate this HeartWeek 2012 Supplement to him.
Aerosolised heparin in the treatment of Fontan-related plastic bronchitis
Authors: Eason Daniel E. , Cox Kristin , Moskowitz William B.
Published: January 2013

Patients with Fontan palliation and single-ventricle physiology encounter multiple comorbidities including plastic bronchitis, a disease characterised by the plugging of small and large airways by rubbery, white casts. To date, no controlled clinical trials have demonstrated effective treatment of plastic bronchitis. We report the application of aerosolised heparin, which has published success in non-cardiac-related pulmonary disease, for this complication in a Fontan patient.
The World Congress of Paediatric Cardiology and Cardiac Surgery: a short factual history by Jane Somerville
Authors: Somerville Jane
Published: January 2013

The World Congress of Paediatric Cardiology and Cardiac Surgery has survived with minimal assets and simple organisation. Each congress is special, taking on the humour, flavour, and culture of the organising country. It is hard work for a few organisers and money is hard to raise. The steering committee works closely, fairly, and successfully, and even though accused of being secretive and effete that does not matter. It is efficient and produces successful, happy world congresses, where all involved with the speciality are welcome. With so many “grown-ups” with congenital heart disease, it is no longer just a paediatric problem – maybe the name of this congress must change again. Regardless, the flag must fly on.
Cancer risk among patients with congenital heart defects: a nationwide follow-up study
Authors: Olsen Morten , Garne Ester , Sværke Claus , Søndergaard Lars , Nissen Henrik , Andersen Henrik Ø. , Hjortdal Vibeke E. , Johnsen Søren P. , Videbæk Jørgen
Published: January 2013

Objective

We aimed to assess cancer risk in congenital heart defect patients, with and without Down's syndrome, compared with the general population.

Methods

We identified all patients born and diagnosed with congenital heart defects from 1977 to 2008 using the Danish National Registry of Patients, covering all Danish hospitals. We compared cancer incidence in the congenital heart defect cohort with that expected in the general population (∼5.5 million) using the Danish Cancer Registry, and computed age- and gender-standardised incidence ratios.

Results

We identified 15,905 congenital heart defect patients, contributing a total of 151,172 person-years at risk; the maximum length of follow-up was 31 years (median 8 years). In all, 53 patients were diagnosed with cancer, including 30 female and 23 male patients (standardised incidence ratio = 1.63; 95% confidence interval: 1.22–2.13). Risks were increased for leukaemia, brain tumours, and basal cell carcinoma. After excluding 801 patients with Down's syndrome, the standardised incidence ratio was 1.19 (95% confidence interval: 0.84–1.64). In the subgroup of 5660 non-Down's syndrome patients undergoing cardiac surgery or catheter-based interventions, the standardised incidence ratio was 1.45 (95% confidence interval: 0.86–2.29).

Conclusion

The overall risk of cancer among congenital heart defect patients without Down's syndrome was not statistically significantly elevated. Cancer risk in the congenital heart defect cohort as a whole, including patients with Down's syndrome, was increased compared with the general population, although the absolute risk was low. Studies with longer follow-up and more information on radiation doses are needed to further examine a potential cancer risk associated with diagnostic radiation exposure.
Auditory Hallucinations and Reduced Language Lateralization in Schizophrenia: A Meta-analysis of Dichotic Listening Studies
Authors: Ocklenburg Sebastian , Westerhausen René , Hirnstein Marco , Hugdahl Kenneth
Published: January 2013

Reduced left-hemispheric language lateralization has been proposed to be a trait marker for schizophrenia, but the empirical evidence is ambiguous. Recent studies suggest that auditory hallucinations are critical for whether a patient shows reduced language lateralization. Therefore, the aim of the study was to statistically integrate studies investigating language lateralization in schizophrenia patients using dichotic listening. To this end, two meta-analyses were conducted, one comparing schizophrenia patients with healthy controls (n = 1407), the other comparing schizophrenia patients experiencing auditory hallucinations with non-hallucinating controls (n = 407). Schizophrenia patients showed weaker language lateralization than healthy controls but the effect size was small (g = −0.26). When patients with auditory hallucinations were compared to non-hallucinating controls, the effect size was substantially larger (g = −0.45). These effect sizes suggest that reduced language lateralization is a weak trait marker for schizophrenia as such and a strong trait marker for the experience of auditory hallucinations within the schizophrenia population. (JINS, 2013, 19, 1–9.)
The economic and environmental effects of an EU ban on illegal logging imports. Insights from a CGE assessment
Authors: Bosello Francesco , Parrado Ramiro , Rosa Renato
Published: January 2013

The European Union (EU) is now discussing a legislation proposal to ban illegal timber from the EU market. We use the ICES model to estimate the reallocation of global demand and timber imports following the EU legislation. We aim to assess the economic impacts and measure the potential emission reduction resulting from the introduction of this policy. Results show that an EU ban targeting only log imports is not effective in reducing illegal logging, but its main effect is the removal of illegal logs from international markets. Additionally, the unilateral EU ban increases secondary wood production in illegal logging countries as their exports become relatively more competitive. Through this mechanism, part of the banned illegal timber will re-enter international trade flows ‘hidden’ as processed wood. Extending the ban to timber processed products eliminates this effect and reinforces direct carbon emissions reduction from logging activities.
Novel Method for Controlled Wetting of Materials in the Environmental Scanning Electron Microscope
Authors: Jansson Anna , Nafari Alexandra , Sanz-Velasco Anke , Svensson Krister , Gustafsson Stefan , Hermansson Anne-Marie , Olsson Eva
Published: January 2013

Environmental scanning electron microscopy has been extensively used for studying the wetting properties of different materials. For some types of investigation, however, the traditional ways of conducting in situ dynamic wetting experiments do not offer sufficient control over the wetting process. Here, we present a novel method for controlled wetting of materials in the environmental scanning electron microscope (ESEM). It offers improved control of the point of interaction between the water and the specimen and renders it more accessible for imaging. It also enables the study of water transport through a material by direct imaging. The method is based on the use of a piezo-driven nanomanipulator to bring a specimen in contact with a water reservoir in the ESEM chamber. The water reservoir is established by local condensation on a Peltier-cooled surface. A fixture was designed to make the experimental setup compatible with the standard Peltier cooling stage of the microscope. The developed technique was successfully applied to individual cellulose fibers, and the absorption and transport of water by individual cellulose fibers were imaged.
Four weeks lithium treatment alters neuronal dendrites in the rat hippocampus
Authors: Shim Seong S. , Hammonds Michael D. , Mervis Ronald F.
Published: January 2013

A large body of evidence from molecular, cellular and human studies suggests that lithium may enhance synaptic plasticity, which may be associated with its therapeutic efficacy. However, only a small number of studies have directly assessed this. To determine whether lithium treatment alters structural synaptic plasticity, this study examined the effect of 4 wk lithium treatment on the amount and distribution of dendrites in the dentate gyrus (DG) and hippocampal area CA1 of young adult rats. Following 4 wk lithium or control chow feeding, animals were decapitated, the hippocampi were prepared and stained using a rapid Golgi staining technique and the amount and distribution of the dendritic branching was evaluated using Sholl analyses (method of concentric circles). In the DG, lithium treatment increased the amount and distribution of dendritic branches in the proximal half of dendritic trees of the granule cells and reduced branching in the distal half. In area CA1, the same treatment also increased the number of dendritic branches in the proximal half of apical dendritic trees of CA1 pyramidal cells and reduced branching in the distal half of apical dendritic trees but had no effect on basilar dendritic trees. The lithium treatment altered the total density of dendritic trees in neither the DG nor area CA1. These findings suggest that, in the DG and apical CA1, chronic lithium treatment rearranges neuronal morphology to increase dendritic branching and distribution to where major afferent input is received.
Low dose risperidone attenuates cue-induced but not heroin-induced reinstatement of heroin seeking in an animal model of relapse
Authors: Lai Miaojun , Chen Weisheng , Zhu Huaqiang , Zhou Xiaoli , Liu Huifen , Zhang Fuqiang , Zhou Wenhua
Published: January 2013

The aim of the present study was to investigate the effects of pretreatment with risperidone on heroin self-administration and heroin-seeking behaviour induced by cues and heroin priming. Rats were trained to self-administer heroin under a fixed ratio 1 schedule for 2 wk and nose-poke responding was extinguished for 10 d, after which reinstatement of drug seeking was induced by conditioned cues or heroin priming. Acute risperidone administration at doses 10–100 µg/kg potently and dose-dependently inhibited reinstatement of conditioned cue-induced heroin seeking; the minimum dose of inhibition was 30 µg/kg. In contrast, risperidone at the same doses did not attenuate reinstatement induced by two priming doses of heroin (100 or 250 µg/kg s.c.). Risperidone at these doses failed to alter heroin self-administration and locomotion activity. These data demonstrate that acute treatment with low-dose risperidone inhibits conditioned cue-induced heroin seeking and risperidone may be an adjunctive therapy for the treatment of heroin addiction.
CULTURAL CONSTRUCTION AND A NEW ETHNIC GROUP MOVEMENT: THE CASE OF THE SAKIZAYA IN EASTERN TAIWAN
Authors: Huang 黃宣衛 Shiun-wey
Published: January 2013

After the Kuomintang of China (KMT) succeeded the Japanese government in Taiwan in 1945, officials continued to apply the then current method of categorizing Taiwanese aborigines into nine groups. However, since the 1980s, many aboriginal groups have launched Name Rectification Campaigns calling for “independence” from their originally designated groups.

Dutch records in the seventeenth century identify the Sakizaya as a distinct people, different from the Amis. The decline of the Sakizaya was initiated in 1878 by the Jia-Li-Wan event. After defeat by Qing soldiers, the Sakizayas obscured their identities by mixing themselves among the Amis. By the time that the Japanese began their ethnographic research in the early twentieth century, the Sakizayas had become relatively “Amis-ized,” and were regarded as a sub-branch of the Amis for both academic and official purposes. The Sakizaya's new ethnic group movement was initiated in 1990. Seventeen years later, on January 17, 2007, the Sakizaya gained official recognition as an independent aboriginal group.

This article intends to investigate the strategies of movement activists. It not only examines the concept of cultural construction, but also explains why this concept is so important in understanding the case of the Sakizaya.
Endogenous electric currents might guide rostral migration of neuroblasts
Authors: Cao Lin , Wei Dongguang , Reid Brian , Zhao Siwei , Pu Jin , Pan Tingrui , Yamoah Ebenezer N , Zhao Min
Published: January 2013

Mechanisms that guide directional migration of neuroblasts from the subventricular zone (SVZ) are not well understood. We report here that endogenous electric currents serve as a guidance cue for neuroblast migration. We identify the existence of naturally occurring electric currents (1.5±0.6 μA/cm2, average field strength of ∼3 mV/mm) along the rostral migration path in adult mouse brain. Electric fields of similar strength direct migration of neuroblasts from the SVZ in culture and in brain slices. The purinergic receptor P2Y1 mediates this migration. The results indicate that naturally occurring electric currents serve as a new guidance mechanism for rostral neuronal migration.
Adaptive Changes in the Neuronal Proteome: Mitochondrial Energy Production, Endoplasmic Reticulum Stress, and Ribosomal Dysfunction in the Cellular Response to Metabolic Stress
Authors: Herrmann Abigail G , Deighton Ruth F , Bihan Thierry Le , McCulloch Mailis C , Searcy James L , Kerr Lorraine E , McCulloch James
Published: January 2013

Impaired energy metabolism in neurons is integral to a range of neurodegenerative diseases, from Alzheimer's disease to stroke. To investigate the complex molecular changes underpinning cellular adaptation to metabolic stress, we have defined the proteomic response of the SH-SY5Y human neuroblastoma cell line after exposure to a metabolic challenge of oxygen glucose deprivation (OGD) in vitro. A total of 958 proteins across multiple subcellular compartments were detected and quantified by label-free liquid chromatography mass spectrometry. The levels of 130 proteins were significantly increased ( P < 0.01) after OGD and the levels of 63 proteins were significantly decreased ( P < 0.01) while expression of the majority of proteins (765) was not altered. Network analysis identified novel protein–protein interactomes involved with mitochondrial energy production, protein folding, and protein degradation, indicative of coherent and integrated proteomic responses to the metabolic challenge. Approximately one third (61) of the differentially expressed proteins was associated with the endoplasmic reticulum and mitochondria. Electron microscopic analysis of these subcellular structures showed morphologic changes consistent with the identified proteomic alterations. Our investigation of the global cellular response to a metabolic challenge clearly shows the considerable adaptive capacity of the proteome to a slowly evolving metabolic challenge.
Phenelzine Mitochondrial Functional Preservation and Neuroprotection after Traumatic Brain Injury Related to Scavenging of the Lipid Peroxidation-Derived Aldehyde 4-Hydroxy-2-Nonenal
Authors: Singh Indrapal N , Gilmer Lesley K , Miller Darren M , Cebak John E , Wang Juan A , Hall Edward D
Published: January 2013

Phenelzine (PZ) is a scavenger of the lipid peroxidation (LP)-derived reactive aldehyde 4-hydroxynonenal (4-HNE) due to its hydrazine functional group, which can covalently react with 4-HNE. In this study, we first examined the ability of PZ to prevent the respiratory depressant effects of 4-HNE on normal isolated brain cortical mitochondria. Second, in rats subjected to controlled cortical impact traumatic brain injury (CCI-TBI), we evaluated PZ (10 mg/kg subcutaneously at 15 minutes after CCI-TBI) to attenuate 3-hour post-TBI mitochondrial respiratory dysfunction, and in separate animals, to improve cortical tissue sparing at 14 days. While 4-HNE exposure inhibited mitochondrial complex I and II respiration in a concentration-dependent manner, pretreatment with equimolar concentrations of PZ antagonized these effects. Western blot analysis demonstrated a PZ decrease in 4-HNE in mitochondrial proteins. Mitochondria isolated from peri-contusional brain tissue of CCI-TBI rats treated with vehicle at 15 minutes after injury showed a 37% decrease in the respiratory control ratio (RCR) relative to noninjured mitochondria. In PZ-treated rats, RCR suppression was prevented ( P < 0.05 versus vehicle). In another cohort, PZ administration increased spared cortical tissue from 86% to 97% ( P < 0.03). These results suggest that PZ's neuroprotective effect is due to mitochondrial protection by scavenging of LP-derived 4-HNE.
Building a Cochlear Implant Practice: Five Lessons Learned
Authors: Lobdell Anne M. , Dansie Joseph E. , Ferguson Sarah Hargus
Published: January 2013

Cochlear implants are becoming available to an increasing proportion of the deaf and hard-of-hearing population. As interest in and success with cochlear implants has grown, more and more private practice clinics are incorporating them into their scopes of practice. Over the past 2 years, the first 2 authors of this article have been heavily involved in developing cochlear implant programs in separate otolaryngology private practices. A recent conversation about this process revealed several common experiences and lessons learned. During these same 2 years, the third author began teaching the cochlear implant course at the University of Utah. Although her audiology and speech science background gave her extensive knowledge of the science behind cochlear implants, she had no clinical experience with them. The first author took this course the first time the third author taught it, and the experiences and insights she shared with the third author during and since the course have been an important component of the third author’s personal education in the clinical aspects of cochlear implants. In this article, the first 2 authors share 5 things we wish we had known when first beginning their work with cochlear implants.
Considerations in Mapping Young Children With Simultaneous/Sequential Bilateral CIs: Case Studies
Authors: Vasil-Dilaj Kristin , Brackett Diane
Published: January 2013

In this article, we present three case studies of young children with profound sensorineural hearing loss who received bilateral cochlear implants. In each of these cases, specialists suspected interference between the ears. The audiologist and speech-language pathologist determined that the children had better auditory function and speech and language production when wearing 1 speech processor as opposed to 2 speech processors. In many pediatric implantation cases, experts verify the device fitting in the bilateral condition because infants and toddlers at the prelanguage level are unable to provide specific input during mapping sessions. The cases we describe herein highlight the need for individual ear verification at early stages of speech and language development. In addition, based on these cases, we propose mapping changes that can be made to optimize binaural listening for speech and language development.
Evidence-Based Practice & Practice-Based Evidence Applied to Adult, Medical Speech-Language Pathology
Authors: Lemoncello Rik , Ness Bryan
Published: January 2013

In this paper, we review concepts of evidence-based practice (EBP), and provide a discussion of the current limitations of EBP in terms of a relative paucity of efficacy evidence and the limitations of applying findings from randomized controlled clinical trials to individual clinical decisions. We will offer a complementary model of practice-based evidence (PBE) to encourage clinical scientists to design, implement, and evaluate our own clinical practices with high-quality evidence. We will describe two models for conducting PBE: the multiple baseline single-case experimental design and a clinical case study enhanced with generalization and control data probes. Gathering, analyzing, and sharing high-quality data can offer additional support through PBE to support EBP in speech-language pathology. It is our hope that these EBP and PBE strategies will empower clinical scientists to persevere in the quest for best practices.
Dielectrophoresis has broad applicability to marker-free isolation of tumor cells from blood by microfluidic systems
Authors: Shim Sangjo , Stemke-Hale Katherine , Noshari Jamileh , Becker Frederick F. , Gascoyne Peter R. C.
Published: January 2013

The number of circulating tumor cells (CTCs) found in blood is known to be a prognostic marker for recurrence of primary tumors, however, most current methods for isolating CTCs rely on cell surface markers that are not universally expressed by CTCs. Dielectrophoresis (DEP) can discriminate and manipulate cancer cells in microfluidic systems and has been proposed as a molecular marker-independent approach for isolating CTCs from blood. To investigate the potential applicability of DEP to different cancer types, the dielectric and density properties of the NCI-60 panel of tumor cell types have been measured by dielectrophoretic field-flow fractionation (DEP-FFF) and compared with like properties of the subpopulations of normal peripheral blood cells. We show that all of the NCI-60 cell types, regardless of tissue of origin, exhibit dielectric properties that facilitate their isolation from blood by DEP. Cell types derived from solid tumors that grew in adherent cultures exhibited dielectric properties that were strikingly different from those of peripheral blood cell subpopulations while leukemia-derived lines that grew in non-adherent cultures exhibited dielectric properties that were closer to those of peripheral blood cell types. Our results suggest that DEP methods have wide applicability for the surface-marker independent isolation of viable CTCs from blood as well as for the concentration of leukemia cells from blood.
Landau-Placzek ratio for heat density dynamics and its application to heat capacity of liquids
Authors: Bryk Taras , Ruocco Giancarlo , Scopigno Tullio
Published: January 2013

Exact relation for contributions to heat capacity of liquids is obtained from hydrodynamic theory. It is shown from analysis of the long-wavelength limit of heat density autocorrelation functions that the heat capacity of simple liquids is represented as a sum of two contributions due to “phonon-like” collective excitations and heat relaxation. The ratio of both contributions being the analogy of Landau-Placzek ratio for heat processes depends on the specific heats ratio. The theory of heat density autocorrelation functions in liquids is verified by computer simulations. Molecular dynamics simulations for six liquids having the ratio of specific heats γ in the range 1.1–2.3, were used for evaluation of the heat density autocorrelation functions and predicted Landau-Placzek ratio for heat processes. The dependence of contributions from collective excitations and heat relaxation process to specific heat on γ is shown to be in excellent agreement with the theory.
Fast and slow transient charging in various III-V field-effect transistors with atomic-layer-deposited-Al2O3 gate dielectric
Authors: Ramón Michael E. , Akyol Tarik , Shahrjerdi Davood , Young Chadwin D. , Cheng Julian , Register Leonard F. , Banerjee Sanjay K.
Published: January 2013

We report measurement of fast transient charging effects (FTCE) in enhancement-mode n-channel GaAs, InP, and In0.53Ga0.47As field-effect transistors (FETs) using Al2O3 as the gate dielectric. The FTCE data reveal superior drive current and enhanced threshold voltage stability for In0.53Ga0.47As FETs. We further report charge pumping measurements for In0.53Ga0.47As transistors, revealing that the majority of interface traps are donor traps, as well as an increased trap density within the Al2O3 bulk. Such data, together with FTCE data, reveal that drain current degradation observed during pulsed I-V measurements is predominantly due to slow oxide traps, underscoring their significance within III-V/high-κ metal-oxide-semiconductor FETs.
Thermoelastic response of thin metal films and their adjacent materials
Authors: Kang S. , Yoon Y. , Kim J. , Kim W.
Published: January 2013

A pulsed laser beam applied to a thin metal film is capable of launching an acoustic wave due to thermal expansion. Heat transfer from the thin metal film to adjacent materials can also induce thermal expansion; thus, the properties of these adjacent materials (as well as the thin metal film) should be considered for a complete description of the thermoelastic response. Here, we show that adjacent materials with a small specific heat and large thermal expansion coefficient can generate an enhanced acoustic wave and we demonstrate a three-fold increase in the peak pressure of the generated acoustic wave on substitution of parylene for polydimethylsiloxane.
Edge effect enhanced electron field emission in top assembled reduced graphene oxide assisted by amorphous CNT-coated carbon cloth substrate
Authors: Roy Rajarshi , Jha Arunava , Banerjee Diptonil , Sankar Das Nirmalya , Chattopadhyay Kalyan Kumar
Published: January 2013

In this work a hybrid structure assembly of amorphous carbon nanotubes (a-CNTs) -reduced graphene oxide (RGO) has been fabricated on carbon cloth/PET substrates for enhanced edge effect assisted flexible field emission device application. The carbon nanostructures prepared by chemical processes were finally deposited one over the other by a simple electrophoretic deposition (EPD) method on carbon cloth (CC) fabric. The thin films were then characterized by X-ray diffraction (XRD), Fourier transformed infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM) and high resolution transmission electron microscope (HRTEM). Field assisted electron emission measurement was performed on this hybrid structure. It was observed that the hybrid carbon nanostructure showed exceptional field emission properties with outstanding low turn-on and threshold field (Eto∼ 0.26 Vμm−1, Eth ∼ 0.55 Vμm1). These observed results are far better compared to standalone and plasma etched edge enhanced RGO systems due to the bottom layer a-CNTs bed which assisted in significant enhancement of edge effect in RGO sheets.
Critical roles of type III phosphatidylinositol phosphate kinase in murine embryonic visceral endoderm and adult intestine
Authors: Takasuga Shunsuke , Horie Yasuo , Sasaki Junko , Sun-Wada Ge-Hong , Kawamura Nobuyuki , Iizuka Ryota , Mizuno Katsunori , Eguchi Satoshi , Kofuji Satoshi , Kimura Hirotaka , Yamazaki Masakazu , Horie Chihoko , Odanaga Eri , Sato Yoshiko , Chida Shinsuke , Kontani Kenji , Harada Akihiro , Katada Toshiaki , Suzuki Akira , Wada Yoh , Ohnishi Hirohide , Sasaki Takehiko
Published: January 2013

The metabolism of membrane phosphoinositides is critical for a variety of cellular processes. Phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P
2
] controls multiple steps of the intracellular membrane trafficking system in both yeast and mammalian cells. However, other than in neuronal tissues, little is known about the physiological functions of PtdIns(3,5)P
2
in mammals. Here, we provide genetic evidence that type III phosphatidylinositol phosphate kinase (PIPKIII), which produces PtdIns(3,5)P
2
, is essential for the functions of polarized epithelial cells. PIPKIII-null mouse embryos die by embryonic day 8.5 because of a failure of the visceral endoderm to supply the epiblast with maternal nutrients. Similarly, although intestine-specific PIPKIII-deficient mice are born, they fail to thrive and eventually die of malnutrition. At the mechanistic level, we show that PIPKIII regulates the trafficking of proteins to a cell’s apical membrane domain. Importantly, mice with intestine-specific deletion of PIPKIII exhibit diarrhea and bloody stool, and their gut epithelial layers show inflammation and fibrosis, making our mutants an improved model for inflammatory bowel diseases. In summary, our data demonstrate that PIPKIII is required for the structural and functional integrity of two different types of polarized epithelial cells and suggest that PtdIns(3,5)P
2
metabolism is an unexpected and critical link between membrane trafficking in intestinal epithelial cells and the pathogenesis of inflammatory bowel disease.
Mechanistic basis of infertility of mouse intersubspecific hybrids
Authors: Bhattacharyya Tanmoy , Gregorova Sona , Mihola Ondrej , Anger Martin , Sebestova Jaroslava , Denny Paul , Simecek Petr , Forejt Jiri
Published: January 2013

Significance

Hybrid sterility contributes to speciation by restricting gene flow between related taxa. Although four hybrid sterility genes have been identified in
Drosophila
and mouse so far, the underlying molecular mechanisms are largely unknown. We describe extensive asynapsis of chromosomes in male and female meiosis of F1 hybrids between two closely related mouse subspecies. Using the intersubspecific chromosome-substitution strains, we demonstrate that the heterospecific pairing of homologous chromosomes is a preexisting condition of asynapsis and may represent a universal mechanism of pachytene arrest in interspecific hybrids. Sex-specific manifestation of asynapsis can explain the mechanism of Haldane’s rule.
The corpus, its users and their needs
Authors: Santos Diana , Frankenberg-Garcia Ana
Published: January 2013

COMPARA is a bidirectional parallel corpus of English and Portuguese, currently with 3 million words. The corpus was launched in 2000 and at present it is possibly the largest edited parallel corpus publicly available on the Web, with roughly 6,000 corpus queries per month. This paper summarizes an analysis of six years of corpus use. We begin by looking at user studies for language resources, especially corpora, and then we provide a snapshot of COMPARA’s users and their behaviour based on log analysis. Particular emphasis is given to the language interface preferred by users (Portuguese and English are possible), the choice between the Simple and Complex Search modes, the reasons underlying null-results and behaviour after restricted output. The data has pointed us to cases where COMPARA’s Web interface can be improved, and provided insights about our users and the problems they face, although further studies that distinguish between different kinds of users remain necessary.
Allocating Attention to Distractor Locations is Based on Top-Down Expectations
Authors: Lahav Aya , Tsal Yehoshua
Published: January 2013

Failures of selective attention may be explained by the attentional white bear (AWB) hypothesis maintaining that prior knowledge of distractor location causes attentional allocation to it. The AWB is demonstrated by embedding infrequent trials of two simultaneous dots among flanker trials. The dot at the expected distractor location is perceived as appearing before the dot at the expected empty location, indicating attentional allocation to expected distractor locations. A major requirement of the AWB hypothesis is that it occurs in a top-down manner due to expectations. We devised a variation of the original AWB experiment, which enabled us to differentiate between the top-down and bottom-up contributions. The results show that top-down expectancies, which are a critical part of the AWB characterization, occur independently of bottom-up contributions.
Central Line-Associated Infections as Defined by the Centers for Medicare and Medicaid Services' Hospital-Acquired Condition versus Standard Infection Control Surveillance Why Hospital Compare Seems Conflicted
Authors: Moehring Rebekah W. , Staheli Russell , Miller Becky A. , Chen Luke Francis , Sexton Daniel John , Anderson Deverick John
Published: January 2013

Objective.

To evaluate the concordance of case-finding methods for central line-associated infection as defined by Centers for Medicare and Medicaid Services (CMS) hospital-acquired condition (HAC) compared with traditional infection control (IC) methods.

Setting.

One tertiary care and 2 community hospitals in North Carolina.

Patients.

Adult and pediatric hospitalized patients determined to have central line infection by either case-finding method.

Methods.

We performed a retrospective comparative analysis of infection detected using HAC versus standard IC central line–associated bloodstream infection surveillance from October 1, 2007, through December 31, 2009. One billing and 2 IC databases were queried and matched to determine the number and concordance of cases identified by each method. Manual review of 25 cases from each discordant category was performed. Sensitivity and positive predictive value (PPV) were calculated using IC as criterion standard.

Results.

A total of 1,505 cases were identified: 844 by International Classification of Diseases, Ninth Revision (ICD-9), and 798 by IC. A total of 204 cases (24%) identified by ICD-9 were deemed not present at hospital admission by coders. Only 112 cases (13%) were concordant. HAC sensitivity was 14% and PPV was 55% compared with IC. Concordance was low regardless of hospital type. Primary reasons for discordance included differences in surveillance and clinical definitions, clinical uncertainty, and poor documentation.

Conclusions.

The case-finding method used by CMS HAC and the methods used for traditional IC surveillance frequently do not agree. This can lead to conflicting results when these 2 measures are used as hospital quality metrics.
The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs
Authors: Levine Timothy P. , Daniels Rachel D. , Gatta Alberto T. , Wong Louise H. , Hayes Matthew J.
Published: January 2013

Motivation: Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, also called motor neuron disease, MND) are severe neurodegenerative diseases that show considerable overlap at the clinical and cellular level. The most common single mutation in families with FTD or ALS has recently been mapped to a non-coding repeat expansion in the uncharacterized gene C9ORF72. Although a plausible mechanism for disease is that aberrant C9ORF72 mRNA poisons splicing, it is important to determine the cellular function of C9ORF72, about which nothing is known.

Results: Sensitive homology searches showed that C9ORF72 is a full-length distant homologue of proteins related to Differentially Expressed in Normal and Neoplasia (DENN), which is a GDP/GTP exchange factor (GEF) that activates Rab-GTPases. Our results suggest that C9ORF72 is likely to regulate membrane traffic in conjunction with Rab-GTPase switches, and we propose to name the gene and its product DENN-like 72 (DENNL72).

Supplementary information:  Supplementary data are available at Bioinformatics online.

Contact:  tim.levine@ucl.ac.uk
Searching for virus phylotypes
Authors: Chevenet François , Jung Matthieu , Peeters Martine , de Oliveira Tulio , Gascuel Olivier
Published: January 2013

Motivation: Large phylogenies are being built today to study virus evolution, trace the origin of epidemics, establish the mode of transmission and survey the appearance of drug resistance. However, no tool is available to quickly inspect these phylogenies and combine them with extrinsic traits (e.g. geographic location, risk group, presence of a given resistance mutation), seeking to extract strain groups of specific interest or requiring surveillance.

Results: We propose a new method for obtaining such groups, which we call phylotypes, from a phylogeny having taxa (strains) annotated with extrinsic traits. Phylotypes are subsets of taxa with close phylogenetic relationships and common trait values. The method combines ancestral trait reconstruction using parsimony, with combinatorial and numerical criteria measuring tree shape characteristics and the diversity and separation of the potential phylotypes. A shuffling procedure is used to assess the statistical significance of phylotypes. All algorithms have linear time complexity. This results in low computing times, typically a few minutes for the larger data sets with a number of shuffling steps. Two HIV-1 data sets are analyzed, one of which is large, containing >3000 strains of HIV-1 subtype C collected worldwide, where the method shows its ability to recover known clusters and transmission routes, and to detect new ones.

Availability: This method and companion tools are implemented in an interactive Web interface (www.phylotype.org), which provides a wide choice of graphical views and output formats, and allows for exploratory analyses of large data sets.

Contact:  francois.chevenet@ird.fr, gascuel@lirmm.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Grape RNA-Seq analysis pipeline environment
Authors: Knowles David G. , Röder Maik , Merkel Angelika , Guigó Roderic
Published: January 2013

Motivation: The avalanche of data arriving since the development of NGS technologies have prompted the need for developing fast, accurate and easily automated bioinformatic tools capable of dealing with massive datasets. Among the most productive applications of NGS technologies is the sequencing of cellular RNA, known as RNA-Seq. Although RNA-Seq provides similar or superior dynamic range than microarrays at similar or lower cost, the lack of standard and user-friendly pipelines is a bottleneck preventing RNA-Seq from becoming the standard for transcriptome analysis.

Results: In this work we present a pipeline for processing and analyzing RNA-Seq data, that we have named Grape (Grape RNA-Seq Analysis Pipeline Environment). Grape supports raw sequencing reads produced by a variety of technologies, either in FASTA or FASTQ format, or as prealigned reads in SAM/BAM format. A minimal Grape configuration consists of the file location of the raw sequencing reads, the genome of the species and the corresponding gene and transcript annotation.

Grape first runs a set of quality control steps, and then aligns the reads to the genome, a step that is omitted for prealigned read formats. Grape next estimates gene and transcript expression levels, calculates exon inclusion levels and identifies novel transcripts.

Grape can be run on a single computer or in parallel on a computer cluster. It is distributed with specific mapping and quantification tools, but given its modular design, any tool supporting popular data interchange formats can be integrated.

Availability: Grape can be obtained from the Bioinformatics and Genomics website at: http://big.crg.cat/services/grape.

Contact:  david.gonzalez@crg.eu or roderic.guigo@crg.eu
SBSI: an extensible distributed software infrastructure for parameter estimation in systems biology
Authors: Adams Richard , Clark Allan , Yamaguchi Azusa , Hanlon Neil , Tsorman Nikos , Ali Shakir , Lebedeva Galina , Goltsov Alexey , Sorokin Anatoly , Akman Ozgur E. , Troein Carl , Millar Andrew J. , Goryanin Igor , Gilmore Stephen
Published: January 2013

Summary: Complex computational experiments in Systems Biology, such as fitting model parameters to experimental data, can be challenging to perform. Not only do they frequently require a high level of computational power, but the software needed to run the experiment needs to be usable by scientists with varying levels of computational expertise, and modellers need to be able to obtain up-to-date experimental data resources easily. We have developed a software suite, the Systems Biology Software Infrastructure (SBSI), to facilitate the parameter-fitting process. SBSI is a modular software suite composed of three major components: SBSINumerics, a high-performance library containing parallelized algorithms for performing parameter fitting; SBSIDispatcher, a middleware application to track experiments and submit jobs to back-end servers; and SBSIVisual, an extensible client application used to configure optimization experiments and view results. Furthermore, we have created a plugin infrastructure to enable project-specific modules to be easily installed. Plugin developers can take advantage of the existing user-interface and application framework to customize SBSI for their own uses, facilitated by SBSI’s use of standard data formats.

Availability and implementation: All SBSI binaries and source-code are freely available from http://sourceforge.net/projects/sbsi under an Apache 2 open-source license. The server-side SBSINumerics runs on any Unix-based operating system; both SBSIVisual and SBSIDispatcher are written in Java and are platform independent, allowing use on Windows, Linux and Mac OS X. The SBSI project website at http://www.sbsi.ed.ac.uk provides documentation and tutorials.

Contact: stg@inf.ed.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.
Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED‐HF)
Authors: McMurray John J.V. , Anand Inder S. , Diaz Rafael , Maggioni Aldo P. , O'Connor Christopher , Pfeffer Marc A. , Solomon Scott D. , Tendera Michal , van Veldhuisen Dirk J. , Albizem Moetaz , Cheng Sunfa , Scarlata Debra , Swedberg Karl , Young James B. ,   on behalf of the RED‐HF Committees Investigators
Published: January 2013

Aims

This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED‐HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.

Methods and results

Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED‐HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED‐HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED‐HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED‐HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study‐specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.

Conclusion

The anaemic patients enrolled in RED‐HF were older, moderately to markedly symptomatic, and had extensive co‐morbidity.
Eradication of Plant Pathogens in Forest Nursery Irrigation Water
Authors: Machado Patrícia da S. , Alfenas Acelino C. , Coutinho Marcelo M. , Silva Cláudio M. , Mounteer Ann H. , Maffia Luiz A. , de Freitas Rodrigo G. , Freitas Camila da S.
Published: January 2013

Interest in rational use and reuse of water has increased in recent years, especially in forest nurseries. However, before water can be reused in nurseries, it must be properly treated to eradicate plant pathogens to reduce risks of pathogen dispersal and losses to disease. In the present study, the efficacy of irrigation water treatment by ultrafiltration and conventional physical-chemical treatment was studied to eliminate Botrytis cinerea, Cylindrocladium candelabrum, Ralstonia solanacearum, and Xanthomonas axonopodis, the pathogens most commonly found in Brazilian forest nurseries. Ultrafiltration eradicated over 99% of R. solanacearum, X. axonopodis, and B. cinerea and 100% of C. candelabrum. The few remaining cells or conidia of R. solanacearum and B. cinerea did not induce disease in irrigated rooted cuttings. Flocculation and fast sand filtration used in physical-chemical treatment completely eliminated C. candelabrum but the other pathogens were only removed after chlorination of the filtered water. Both forms of treatment are viable, practical, and safe methods for plant pathogen removal from irrigation water.
Development of a Magnetic Capture Hybridization Real-Time PCR Assay for Detection of TumorigenicAgrobacterium vitisin Grapevines
Authors: Johnson Kameka L. , Zheng Desen , Kaewnum Supaporn , Reid Cheryl Lynn , Burr Thomas
Published: January 2013

Agrobacterium vitis, the causal agent of grape crown gall, can have severe economic effects on grape production. The bacterium survives systemically in vines and, therefore, is disseminated in propagation material. We developed an assay for use in indexing programs that is efficient and sensitive for detecting A. vitis in grape tissue. Initially, real-time polymerase chain reaction (PCR) primers specific for diverse tumorigenic strains of A. vitis were developed using the virD2 gene sequence. To overcome the effects of PCR inhibitors present in plant tissue, DNA extraction methods that included magnetic capture hybridization (MCH), immunomagnetic separation (IMS), and extraction with the Mo Bio Powerfood kit were compared. The assays incorporating MCH or IMS followed by real-time PCR were 10,000-fold more sensitive than direct real-time PCR when tested using boiled bacterial cell suspensions, with detection thresholds of 101CFU/ml compared with 105CFU/ml. DNA extraction with the Powerfood DNA extraction kit was 10-fold more sensitive than direct real-time PCR, with a detection threshold of 104CFU/ml. All three assays were able to detect A. vitis in healthy-appearing grapevine cuttings taken from infected vines.