bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative analysis of multiple cancer prognosis studies with gene expression measurements
Authors: Ma Shuangge , Huang Jian , Wei Fengrong , Xie Yang , Fang Kuangnan
Published: September 2011

Although in cancer research microarray gene profiling studies have been successful in identifying genetic variants predisposing to the development and progression of cancer, the identified markers from analysis of single datasets often suffer low reproducibility. Among multiple possible causes, the most important one is the small sample size hence the lack of power of single studies. Integrative analysis jointly considers multiple heterogeneous studies, has a significantly larger sample size, and can improve reproducibility. In this article, we focus on cancer prognosis studies, where the response variables are progression‐free, overall, or other types of survival. A group minimax concave penalty (GMCP) penalized integrative analysis approach is proposed for analyzing multiple heterogeneous cancer prognosis studies with microarray gene expression measurements. An efficient group coordinate descent algorithm is developed. The GMCP can automatically accommodate the heterogeneity across multiple datasets, and the identified markers have consistent effects across multiple studies. Simulation studies show that the GMCP provides significantly improved selection results as compared with the existing meta‐analysis approaches, intensity approaches, and group Lasso penalized integrative analysis. We apply the GMCP to four microarray studies and identify genes associated with the prognosis of breast cancer. Copyright © 2011 John Wiley & Sons, Ltd.
Software abstractions for mobile RFID‐enabled applications
Authors: Carreton Andoni Lombide , Pinte Kevin , Meuter Wolfgang De
Published: September 2011

Our everyday environments may soon be pervaded with radio frequency identification (RFID) tags integrated in physical objects. These RFID tags can store a digital representation of the physical object and transmit it wirelessly to pervasive, context‐aware applications running on mobile devices. However, communicating with RFID tags is prone to many failures inherent to the technology. This hinders the development of such applications, as traditional programming models require the programmer to deal with the RFID hardware characteristics manually. On the other hand, traditional RFID middleware focuses on limited scenarios in an enterprise context and not on general ubiquitous computing scenarios. In this paper, we extend the ambient‐oriented programming paradigm to program RFID applications, by considering RFID tags as intermittently connected mutable proxy objects hosted on mobile distributed computing devices, and detail our prototype implementation. Copyright © 2011 John Wiley & Sons, Ltd.
School expulsion as a process and an event: Before and after effects on children at risk for school discipline
Authors: Morrison Gale M. , Anthony Suzanne , Storino Meri H. , Cheng Joanna J. , Furlong Michael J. , Morrison Richard L.
Published: September 2011

A better understanding of expulsion as an act, a process, and an educational intervention leads to an entirely different understanding of student behavior and disciplinary consequences.
Synthesis and Crystal Structure of [Li8(H2O)29]­[Sn10O4S20]·2H2O
Authors: Kaib Thomas , Kapitein Manuel , Dehnen Stefanie
Published: September 2011

[Li8(H2O)29][Sn10O4S20]·2H2O (1), which was obtained by an unusual synthesis pathway, represents the Li+ salt of the super‐tetrahedral cluster anion [Sn10O4S20]8–. Due to the distinct hydration tendency of Li+, the crystal structure differs notably from that of a corresponding Cs+ salt. Compound 1 extends the still very fragmentary series of known lithium chalcogenidostannates and crystallizes in the triclinic space group P$\bar{1}$ (No. 2) with a = 11.232(2), b = 13.097(3), c = 23.735(5) Å, α = 102.73(3)°, β = 90.43(3)°, γ = 93.44(3)°, V = 3399.1(12) Å3 at 173 K and Z = 2.
Cytochrome c oxidase: Intermediates of the catalytic cycle and their energy‐coupled interconversion
Authors: Konstantinov Alexander A.
Published: September 2011

Several issues relevant to the current studies of cytochrome c oxidase catalytic mechanism are discussed. The following points are raised. (1) The terminology currently used to describe the catalytic cycle of cytochrome oxidase is outdated and rather confusing. Presumably, it would be revised so as to share nomenclature of the intermediates with other oxygen‐reactive heme enzymes like P450 or peroxidases. (2) A “catalytic cycle” of cytochrome oxidase involving complete reduction of the enzyme by 4 electrons followed by oxidation by O2 is a chimera composed artificially from two partial reactions, reductive and oxidative phases, that never operate together as a true multi‐turnover catalytic cycle. The 4e
− reduction–oxidation cycle would not serve a paradigm for oxygen reduction mechanism and protonmotive function of cytochrome oxidase. (3) The foremost role of the K‐proton channel in the catalytic cycle may consist in securing faultless delivery of protons for heterolytic O–O bond cleavage in the oxygen‐reducing site, minimizing the danger of homolytic scission reaction route. (4) Protonmotive mechanism of cytochrome oxidase may vary notably for the different single‐electron steps in the catalytic cycle.
Frequency of Alzheimer's disease pathology at autopsy in patients with clinical normal pressure hydrocephalus
Authors: Cabral Danielle , Beach Thomas G. , Vedders Linda , Sue Lucia I. , Jacobson Sandra , Myers Kent , Sabbagh Marwan N.
Published: September 2011

Background

Normal pressure hydrocephalus (NPH) is considered to be potentially treatable with the placement of a cerebrospinal fluid (CSF) shunt. However, the procedure has been reported to have variable success, particularly with respect to improving the cognitive impairment in NPH. The presence of neurologic comorbidities, particularly Alzheimer's disease (AD), may contribute to shunt responsiveness. Uncovering the extent to which AD and NPH co‐occur has implications for diagnosis and treatment of NPH. Autopsy studies of patients with NPH during their lifetime would elucidate the frequency of such comorbidities.

Methods

A search of the Sun Health Research Institute Brain Donation Program database was conducted between January 1, 1997 and April 1, 2009 to identify all cases with neuropathologic evidence of dementia as well as those of clinically diagnosed NPH. We reviewed the medical records and brain findings of each NPH case.

Results

Of the 761 cases autopsied over the study interval, 563 were found to have neuropathologic evidence meeting criteria for a dementing illness. Of 563 cases, AD was found exclusively in 313 (56%), and 94 suffered from secondary diagnosis of dementia. Nine of 761 cases were identified with a clinical diagnosis of NPH, which were among the 563 cases with neuropathology of dementing illness at autopsy, representing 1.6% (9/563) of the cases. On review of brain autopsy reports of these nine patients, eight (89%) were found to have AD and one (11%) had progressive supranuclear palsy. Review of the medical records of the nine NPH cases revealed the following clinical comorbidities: five suffered from AD, one from Parkinson's Disease, one from mild cognitive impairment, and one from seizure disorder.

Conclusions

Given the findings of the present study, we support the AD‐NPH theory and posit that AD is a common pathologic comorbidity in the setting of NPH and may preclude cognitive improvement postshunt placement. This may influence the selection of cases for shunting in the future.
Magnetic resonance imaging‐measured atrophy and its relationship to cognitive functioning in vascular dementia and Alzheimer's disease patients
Authors: Logue Mark W. , Posner Holly , Green Richard C. , Moline Margaret , Cupples L. Adrienne , Lunetta Kathryn L. , Zou Heng , Hurt Stephen W. , Farrer Lindsay A. , DeCarli Charles ,   MIRAGE Study Group
Published: September 2011

Background

Recent pathological studies report vascular pathology in clinically diagnosed Alzheimer's disease (AD) and AD pathology in clinically diagnosed vascular dementia (VaD). We compared magnetic resonance imaging (MRI) measures of vascular brain injury (white matter hyperintensities [WMH] and infarcts) with neurodegenerative measures (medial‐temporal atrophy [MTA] and cerebral atrophy [CA]) in clinically diagnosed subjects with either AD or VaD. We then examined relationships among these measures within and between the two groups and their relationship to mental status.

Methods

Semi‐quantitative MRI measures were derived from blind ratings of MRI scans obtained from participants in a research clinical trial of VaD (N = 694) and a genetic epidemiological study of AD (N = 655).

Results

CA was similar in the two groups, but differences in the mean of MTA and WMH were pronounced. Infarcts were significantly associated with CA in VaD but not in AD; MTA and WMH were associated with CA in both. WMH was associated with MTA in both groups; however, MRI infarcts were associated with MTA in VaD but not with MTA in AD patients. MTA was strongly associated with Mini‐Mental State Examination scores in both groups, whereas evidence of a modest association between WMH and Mini‐Mental State Examination scores was seen in VaD patients.

Conclusions

MRI data from two dementia cohorts with differing dementia etiologies find that the clinical consequences of dementia are most strongly associated with cerebral and medial‐temporal atrophy, suggesting that tissue loss is the major substrate of the dementia syndrome.
Dementia and Alzheimer's disease: A new direction. The 2010 Jay L. Foster Memorial Lecture
Authors: Kuller Lewis H. , Lopez Oscar L.
Published: September 2011

Background

The modern era of Alzheimer's disease (AD) research began in the early 1980s with the establishment of AD research centers and expanded research programs at the National Institute on Aging.

Methods

Over the past 30 years, there has been success in defining criteria for AD and dementia, association of important genetic disorders related to premature dementia in families, the association of apolipoprotein‐E4, and measurement of incidence and prevalence and selected risk factors. However, prevention and treatment have been elusive.

Results

The development of new technologies, especially magnetic resonance imaging, positron emission tomography to measure amyloid in vivo in the brain and glucose metabolism, cerebrospinal fluid examination, better genetic markers, large‐scale longitudinal epidemiology studies, and preventive clinical trials has rapidly begun a new era of research that offers opportunities to better understand etiology, that is, determinants of amyloid biology in the brain, neurofibrillary tangles, synaptic loss, and dementia.

Conclusions

There are three major hypotheses related to dementia: amyloid deposition and secondary synaptic loss as a unique disease, vascular injury, and “aging.” New research must be hypothesis‐driven and lead to testable approaches for treatment and prevention.
Detection of Protective Antibody Titers against Feline Panleukopenia Virus, Feline Herpesvirus-1, and Feline Calicivirus in Shelter Cats Using a Point-of-Care ELISA
Authors: DiGangi Brian A , Gray Lauren K , Levy Julie K , Dubovi Edward J , Tucker Sylvia J
Published: September 2011

Serum antibody titers are a useful measurement of protection against infection (feline panleukopenia virus [FPV]) or clinical disease (feline herpesvirus-1 [FHV] and feline calicivirus [FCV]), and their determination has been recommended as part of disease outbreak management in animal shelters. The objective of this study was to determine the sensitivity, specificity, and inter-observer and inter-assay agreement of two semi-quantitative point-of-care assays for the detection of protective antibody titers (PAT) against FPV, FHV and FCV in shelter cats. Low sensitivity for FPV antibodies (28%) rendered a canine point-of-care assay inappropriate for use in cats. The feline point-of-care assay also had low sensitivity (49%) and low negative predictive value (74%) for FPV PAT detection, but was highly accurate in the assessment of FHV and FCV PAT. Improvements in accuracy and repeatability of FPV PAT determination could make this tool a valuable component of a disease outbreak response in animal shelters.
Markers of Feline Leukaemia Virus Infection or Exposure in Cats from a Region of Low Seroprevalence
Authors: Beatty Julia A , Tasker Séverine , Jarrett Oswald , Lam Amy , Gibson Stephanie , Noe-Nordberg Alice , Phillips Angela , Fawcett Anne , Barrs Vanessa R
Published: September 2011

Molecular techniques have demonstrated that cats may harbour feline leukaemia virus (FeLV) provirus in the absence of antigenaemia. Using quantitative real-time polymerase chain reaction (qPCR), p27 enzyme-linked immunosorbent assay (ELISA), anti-feline oncornavirus-associated cell-membrane-antigen (FOCMA) antibody testing and virus isolation (VI) we investigated three groups of cats. Among cats with cytopenias or lymphoma, 2/75 were transiently positive for provirus and anti-FOCMA antibodies were the only evidence of exposure in another. In 169 young, healthy cats, all tests were negative. In contrast, 3/4 cats from a closed household where FeLV was confirmed by isolation, had evidence of infection. Our results support a role for factors other than FeLV in the pathogenesis of cytopenias and lymphoma. There was no evidence of exposure in young cats. In regions of low prevalence, where the positive predictive value of antigen testing is low, qPCR may assist with diagnosis.
The Concepts of Representation
Authors: REHFELD ANDREW
Published: September 2011

In this reply to Jane Mansbridge's “Clarifying the Concept of Representation” in this issue (American Political Science Review 2011). I argue that our main disagreements are conceptual, and are traceable to the attempt to treat the concept of representation as a “single highly complex concept” as Hanna Pitkin once put it. Instead, I argue, it would be more useful to develop the various concepts that emphasize the underlying forms of representation. Against the view that empirical regularity should guide concept formation, I suggest that the failure to find instances of the cases I conceptualize is not itself a reason to reject them. Instead, I argue in favor of concepts that emphasize one side or other of a relationship, rather than treating both sides simultaneously, defending the view that “promissory” and “anticipatory” may usefully describe the activity of “representing” but ought to emphasize only one side of the representative–voter relationship. I also explain why adding substantive accounts of representation to any of Mansbridge's modifying concepts dilutes their practical value. I conclude by indicating the importance of developing concepts that stretch beyond the democratic contexts that feature prominently in her response.
The chemical dynamics of nanosensors capable of single-molecule detection
Authors: Boghossian Ardemis A. , Zhang Jingqing , Le Floch-Yin François T. , Ulissi Zachary W. , Bojo Peter , Han Jae-Hee , Kim Jong-Ho , Arkalgud Jyoti R. , Reuel Nigel F. , Braatz Richard D. , Strano Michael S.
Published: September 2011

Recent advances in nanotechnology have produced the first sensor transducers capable of resolving the adsorption and desorption of single molecules. Examples include near infrared fluorescent single-walled carbon nanotubes that report single-molecule binding via stochastic quenching. A central question for the theory of such sensors is how to analyze stochastic adsorption events and extract the local concentration or flux of the analyte near the sensor. In this work, we compare algorithms of varying complexity for accomplishing this by first constructing a kinetic Monte Carlo model of molecular binding and unbinding to the sensor substrate and simulating the dynamics over wide ranges of forward and reverse rate constants. Methods involving single-site probability calculations, first and second moment analysis, and birth-and-death population modeling are compared for their accuracy in reconstructing model parameters in the presence and absence of noise over a large dynamic range. Overall, birth-and-death population modeling was the most robust in recovering the forward rate constants, with the first and second order moment analysis very efficient when the forward rate is large (>10−3 s−1). The precision decreases with increasing noise, which we show masks the existence of underlying states. Precision is also diminished with very large forward rate constants, since the sensor surface quickly and persistently saturates.
Capillary instability of elliptic liquid jets
Authors: Amini Ghobad , Dolatabadi Ali
Published: September 2011

Instability of a liquid jet issuing from an elliptic nozzle in Rayleigh mode is investigated and its behavior is compared with a circular jet. Mathematical solution of viscous free-surface flow for asymmetric geometry is complicated if 3-D analytical solutions are to be obtained. Hence, one-dimensional Cosserat (directed curve) equations are used which can be assumed as a low order form of Navier-Stokes equations for slender jets. Linear solution is performed using perturbation method. Temporal dispersion equation is derived to find the most unstable wavelength responsible for the jet breakup. The obtained results for a circular jet (i.e., an ellipse with an aspect ratio of one) are compared with the classical results of Rayleigh and Weber for inviscid and viscous cases, respectively. It is shown that in the Rayleigh regime, which is the subject of this research, symmetric perturbations are unstable while asymmetric perturbations are stable. Consequently, spatial analysis is performed and the variation of growth rate under the effect of perturbation frequencies for various jet velocities is demonstrated. Results reveal that in comparison with a circular jet, the elliptic jet is more unstable. Furthermore, among liquid jets with elliptical cross sections, those with larger ellipticities have a larger instability growth rate.
New far-infrared transmitting Te-based chalcogenide glasses
Authors: Wang Guoxiang , Nie Qiuhua , Wang Xunsi , Shen Xiang , Chen Fen , Xu Tiefeng , Dai Shixun , Zhang Xianghua
Published: September 2011

This study reports on the synthesis of tellurium-based glasses that have a wide transmission far beyond the second atmospheric window. Several far-infrared(IR) transmitting glass systems including Ge-In-Te, Ge-Ga-Te, as well as some compositions containing alkali halides (KI, CsI) or metal halides (PbI2, CuI, AgI, CdI2 or ZnI2) are reported. Their glass-forming ability, thermal stability, and IR transmitting property are investigated. The results show that the broad absorption peak in the 15–20 μm disappear in the Fourier-transform infrared (spectrometer) spectra when gallium is replaced by indium. Te-based chalcogenide glasses containing metal-halides show superior glass-forming ability and better thermal stability than those containing alkali halides. Among these glasses, the ΔT of glass composition 65GeTe4-17In2Te6-18AgI can be as great as 115 °C. In ternary system, the glass composition Ge16Te69(AgI)15 (ΔT = 120 °C) is stable enough toward crystallization in combination with broad transmission region and good chemical durability to be drawn into optical fibers.
Functional specificity for high-level linguistic processing in the human brain
Authors: Fedorenko Evelina , Behr Michael K. , Kanwisher Nancy
Published: September 2011

Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.
Study of the excitation mechanisms of the second positive system in the negative glow of a N2–Ar discharge
Authors: Isola L , López M , Gómez B J
Published: September 2011

In an Ar–N2 discharge, the high excitation transfer from Ar(3P2,0) to N2 produces an overpopulation of the high rotational levels of the bands of the second positive system (SPS), and so the spectra interpretation is not straightforward.

This paper presents a fit function for the SPS bands measured in Ar–N2, which allows us to study the excitation process contributions to the N2(C) level.

The procedure was tested in the negative glow of a pulsed Ar–N2 discharge at a pressure of 2.5 Torr, for different mixture concentrations. In this discharge, through the fitting, it was possible to calculate the variation of the N2(C) densities produced by different excitation processes as well as the variation of Ar metastable density.
Inertial fusion experiments and theory
Authors: Mima Kunioki , Tikhonchuk V. , Perlado M.
Published: September 2011

Inertial fusion research is approaching a critical milestone, namely the demonstration of ignition and burn. The world's largest high-power laser, the National Ignition Facility (NIF), is under operation at the Lawrence Livermore National Laboratory (LLNL), in the USA. Another ignition machine, Laser Mega Joule (LMJ), is under construction at the CEA/CESTA research centre in France. In relation to the National Ignition Campaign (NIC) at LLNL, worldwide studies on inertial fusion applications to energy production are growing. Advanced ignition schemes such as fast ignition, shock ignition and impact ignition, and the inertial fusion energy (IFE) technology are under development. In particular, the Fast Ignition Realization Experiment (FIREX) at the Institute of Laser Engineering (ILE), Osaka University, and the OMEGA-EP project at the Laboratory for Laser Energetics (LLE), University Rochester, and the HiPER project in the European Union (EU) for fast ignition and shock ignition are progressing. The IFE technology research and development are advanced in the frameworks of the HiPER project in EU and the LIFE project in the USA. Laser technology developments in the USA, EU, Japan and Korea were major highlights in the IAEA FEC 2010. In this paper, the status and prospects of IFE science and technology are described.
DIII-D contributions towards the scientific basis for sustained burning plasmas
Authors: Greenfield C.M.
Published: September 2011

DIII-D is making significant contributions to a scientific basis for sustained burning plasma operation. These include explorations of increasingly reactor-relevant scenarios, studies of key issues for projecting performance, development of techniques for handling heat and particle efflux, and assessment of key issues for the ITER research plan. Advanced scenarios are being optimized in DIII-D via experiments to empirically determine the relationship between transport and the current profile, which in turn can provide essential input to inform improvement of the theory-based models that do not currently capture the observed behaviour. Joint DIII-D/JET ρ* scans in the hybrid regime imply Bohm-like confinement scaling. Startup and shutdown techniques were developed for the restrictive environment of future devices while retaining compatibility with advanced scenarios. Towards the goal of a fully predictive capability, the DIII-D program emphasizes validation of physics-based models, facilitated by a number of new and upgraded diagnostics. Specific areas include transport, rotation, energetic particles and the H-mode pedestal, but this approach permeates the entire research programme. Concerns for heat and particle efflux in future devices are addressed through studies of ELM control, disruption avoidance and mitigation, and hydrogenic retention in DIII-D's carbon wall. DIII-D continues to respond to specific needs for ITER. Recent studies have compared H-mode access in several different ion species, identifying not only isotopic, but density, rotation and geometrical dependences that may guide access to H-mode during ITER's non-activated early operation. DIII-D used an insertable module to simulate the magnetic perturbations introduced by one of ITER's three test blanket module sets, demonstrating that little impact on performance is seen at ITER equivalent levels of magnetic perturbation.
Effects of 3D magnetic perturbations on toroidal plasmas
Authors: Callen J.D.
Published: September 2011

Small three-dimensional (3D) magnetic field perturbations have many interesting and possibly useful effects on tokamak and quasi-symmetric stellarator plasmas. Plasma transport equations that include these effects, most notably on diamagnetic-level toroidal plasma flows, have recently been developed. The 3D field perturbations and their plasma effects can be classified according to their toroidal mode number n: low n (say 1–5) resonant (with field line pitch, q = m/n) and non-resonant fields, medium n (∼20, due to toroidal field ripple) and high n (due to microturbulence). Low n non-resonant fields induce a neoclassical toroidal viscosity (NTV) that damps toroidal rotation throughout the plasma towards an offset rotation in the counter-current direction. Recent tokamak experiments have generally confirmed and exploited these predictions by applying external low n non-resonant magnetic perturbations. Medium n toroidal field ripple produces similar effects plus possible ripple-trapping NTV effects and ion direct losses in the edge. A low n (e.g. n = 1) resonant field is mostly shielded by the toroidally rotating plasma at and inside the resonant (rational) surface. If it is large enough it can stop plasma rotation at the rational surface, facilitate magnetic reconnection there and lead to a growing stationary magnetic island (locked mode), which often causes a plasma disruption. Externally applied 3D magnetic perturbations usually have many components. In the plasma their lowest n (e.g. n = 1) externally resonant components can be amplified by kink-type plasma responses, particularly at high β. Low n plasma instabilities (e.g. resistive wall modes, neoclassical tearing modes) cause additional 3D magnetic perturbations in tokamak plasmas. Tearing modes in their nonlinear (Rutherford) regime bifurcate the topology and form magnetic islands. Finally, multiple resonant magnetic perturbations (RMPs) can, if not shielded by plasma rotation effects, cause local magnetic stochasticity and increase plasma transport in the edge of H-mode plasmas. These various effects of 3D fields can be used to modify directly the plasma toroidal rotation (and possibly transport via multiple RMPs for controlling edge localized modes) and indirectly anomalous plasma transport. The present understanding and modelling of these various 3D magnetic field perturbation effects including for test blanket modules in ITER are summarized. Finally, implications of the present understanding and key open issues for developing a predictive capability of them for ITER are discussed.
PepCrawler: a fast RRT-based algorithm for high-resolution refinement and binding affinity estimation of peptide inhibitors
Authors: Donsky Elad , Wolfson Haim J.
Published: September 2011

Motivation: Design of protein–protein interaction (PPI) inhibitors is a key challenge in structural bioinformatics and computer-aided drug design. Peptides, which partially mimic the interface area of one of the interacting proteins, are natural candidates to form protein–peptide complexes competing with the original PPI. The prediction of such complexes is especially challenging due to the high flexibility of peptide conformations.

Results: In this article, we present PepCrawler, a new tool for deriving binding peptides from protein–protein complexes and prediction of peptide–protein complexes, by performing high-resolution docking refinement and estimation of binding affinity. By using a fast path planning approach, PepCrawler rapidly generates large amounts of flexible peptide conformations, allowing backbone and side chain flexibility. A newly introduced binding energy funnel ‘steepness score’ was applied for the evaluation of the protein–peptide complexes binding affinity. PepCrawler simulations predicted high binding affinity for native protein–peptide complexes benchmark and low affinity for low-energy decoy complexes. In three cases, where wet lab data are available, the PepCrawler predictions were consistent with the data. Comparing to other state of the art flexible peptide–protein structure prediction algorithms, our algorithm is very fast, and takes only minutes to run on a single PC.

Availability:  http://bioinfo3d.cs.tau.ac.il/PepCrawler/

Contact:  eladdons@tau.ac.il; wolfson@tau.ac.il
Genetic Variants and Susceptibility to Neurological Complications Following West Nile Virus Infection
Authors: Loeb Mark , Eskandarian Sasha , Rupp Mark , Fishman Neil , Gasink Leanne , Patterson Jan , Bramson Jonathan , Hudson Thomas J , Lemire Mathieu
Published: September 2011

To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10−5; odds ratio [OR], 0.68 [95% confidence interval {CI}, .56–.81]); rs2298771 in SCN1A (sodium channel, neuronal type I α subunit) (P = 5.87 × 10−5; OR, 1.47 [95% CI, 1.21–1.77]); and rs25651 in ANPEP (ananyl aminopeptidase) (P = 1.44 × 10−4; OR, 0.69 [95% CI, .56–.83]). Additional genotyping of these SNPs in a separate sample of 264 case patients and 296 control patients resulted in a lack of significance in the replication cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P = .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did not identify genetic variants associated with neuroinvasive disease.
Trophic links between functional groups of arable plants and beetles are stable at a national scale
Authors: Brooks David R. , Storkey Jonathan , Clark Suzanne J. , Firbank Les G. , Petit Sandrine , Woiwod Ian P.
Published: September 2011

1. There is an urgent need to accurately model how environmental change affects the wide‐scale functioning of ecosystems, but advances are hindered by a lack of knowledge of how trophic levels are linked across space. It is unclear which theoretical approach to take to improve modelling of such interactions, but evidence is gathering that linking species responses to their functional traits can increase understanding of ecosystem dynamics. Currently, there are no quantitative studies testing how this approach might improve models of multiple, trophically interacting species, at wide spatial scales.

2. Arable weeds play a foundational role in linking food webs, providing resources for many taxa, including carabid beetles that feed on their seeds and weed‐associated invertebrate prey. Here, we model associations between weeds and carabids across farmland in Great Britain (GB), to test the hypothesis that wide‐scale trophic links between these groups are structured by their species functional traits.

3. A network of c. 250 arable fields, covering four crops and most lowland areas of GB, was sampled for weed, carabid and invertebrate taxa over 3 years. Data sets of these groups were closely matched in time and space, and each contained numerous species with a range of eco‐physiological traits. The consistency of trophic linkages between multiple taxa sharing functional traits was tested within multivariate and log‐linear models.

4. Robust links were established between the functional traits of taxa and their trophic interactions. Autumn‐germinating, small‐seeded weeds were associated with smaller, spring‐breeding carabids, more specialised in seed feeding, whereas spring‐germinating, large‐seeded weeds were associated with a range of larger, autumn‐breeding omnivorous carabids. These relationships were strong and dynamic, being independent of changes in invertebrate food resources and consistent across sample dates, crops and regions of GB.

5. We conclude that, in at least one system of interacting taxa, functional traits can be used to predict consistent, wide‐scale trophic links. This conceptual approach is useful for assessing how perturbations affecting lower trophic levels are ramified throughout ecosystems and could be used to assess how environmental change affects a wider range of secondary consumers.
Fathers of children with disabilities: encounters with health professionals in a Chinese context
Authors: Huang Yu‐Ping , Tsai Sen‐Wei , Kellett Ursula
Published: September 2011

Aims.  The aim of this study was to examine the experiences of fathers of developmentally disabled children during interactions with health professionals in Taiwan.

Background.  The role of Chinese fathers in raising a disabled child has been neglected because most studies on the impact of parenting a child with disabilities in this culture have primarily focused on mothers.

Design.  A hermeneutic phenomenological approach was undertaken to recover and interpret fathers’ experiences.

Method.  Sixteen fathers living with their disabled child (0–18 years old) were purposively recruited from a teaching hospital in central Taiwan. Data were collected using in‐depth interviews and journal notes. All participants were interviewed twice. Interviews lasted from 50–100 minutes, and all were recorded.

Results.  Three shared meanings were attributed to fathers’ interactions with health professionals: (1) experiencing no supportive communication, (2) missing the critical time for disability management and (3) being excluded from medical decision making.

Conclusions.  Fathers in Taiwan commonly rely on health professionals to solve their child’s health problems owing to their perceived power to cure and their professional authority in Chinese society. However, fathers felt powerless and hopeless when they received unclear information and incorrect diagnoses, which delayed appropriate treatment. Expressions of dissatisfaction and possessing a sense of futility were common experiences related to exclusion in a paternalistic healthcare system.

Relevance to clinical practice.  Taiwanese clinicians’ attitudes and parental–professional relationships challenge an exploration of ethics and standards of medical care shaped by Chinese culture. Ways of promoting parental inclusion in decision making and care, in particular father’s inclusion, need to be explored. Recognition of the Chinese mother and father and their differing parental healthcare experiences are important to understand to ensure improvement in encounters with health professionals and the maximisation of positive health outcomes.
Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis
Authors: von Rüden E.‐L. , Avemary J. , Zellinger C. , Algermissen D. , Bock P. , Beineke A. , Baumgärtner W. , Stein V. M. , Tipold A. , Potschka H.
Published: September 2011

E.‐L. von Rüden, J. Avemary, C. Zellinger, D. Algermissen, P. Bock, A. Beineke, W. Baumgärtner, V. M. Stein, A. Tipold and H. Potschka (2012) Neuropathology and Applied Neurobiology38, 426–442

Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis

Aims: Despite knowledge about the impact of brain inflammation on hippocampal neurogenesis, data on the influence of virus encephalitis on dentate granule cell neurogenesis are so far limited. Canine distemper is considered an interesting model of virus encephalitis, which can be associated with a chronic progressing disease course and can cause symptomatic seizures. Methods: To determine the impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we compared post‐mortem tissue from dogs with infection with and without seizures, from epileptic dogs with non‐viral aetiology and from dogs without central nervous system diseases. Results: The majority of animals with infection and with epilepsy of non‐viral aetiology exhibited neuronal progenitor numbers below the age average in controls. Virus infection with and without seizures significantly decreased the mean number of neuronal progenitor cells by 43% and 76% as compared to age‐matched controls. Ki‐67 labelling demonstrated that hippocampal cell proliferation was neither affected by infection nor by epilepsy of non‐viral aetiology. Analysis of CDV infection in cells expressing caspase‐3, doublecortin or Ki‐67 indicated that infection of neuronal progenitor cells is extremely rare and suggests that infection might damage non‐differentiated progenitor cells, hamper neuronal differentiation and promote glial differentiation. A high inter‐individual variance in the number of lectin‐reactive microglial cells was evident in dogs with distemper infection. Statistical analyses did not reveal a correlation between the number of lectin‐reactive microglia cells and neuronal progenitor cells. Conclusions: Our data demonstrate that virus encephalitis with and without seizures can exert detrimental effects on hippocampal neurogenesis, which might contribute to long‐term consequences of the disease. The lack of a significant impact of distemper virus on Ki‐67‐labelled cells indicates that the infection affected neuronal differentiation and survival of newborn cells rather than hippocampal cell proliferation.
Regulation of stem cell differentiation in adipose tissue by chronic inflammation
Authors: Ye Jianping , Gimble Jeffery M
Published: September 2011

1. Recent studies suggest that a local hypoxic response leads to chronic inflammation in the adipose tissue of obese individuals. The adipose tissue hypoxia may reflect a compensatory failure in the local vasculature system in response to obesity.

2. Studies suggest that inflammation stimulates angiogenesis and inhibits adipocyte activities in a feedback manner within the obese adipose tissue. Adipose‐derived stem cells (ASC) are able to differentiate into multiple lineages of progenitor cells for adipocytes, endothelial cells, fibroblasts and pericytes. Differentiation of ASC into those progenitors is regulated by the adipose tissue microenvironment.

3. As a major factor in the microenvironment, inflammation may favour ASC differentiation into endothelial cells through the induction of angiogenic factors. At the same time, inflammation inhibits ASC differentiation into adipocytes by suppressing peroxisome proliferator‐activated receptor γ activity and the insulin signalling pathway. In this context, inflammation may serve as a signal mediating the competition between adipocytes and endothelial cells for the limited source of ASC.

4. It is a new concept that inflammation mediates signals in the competition between adipocytes and endothelial cells for the limited ASC in obesity. There is a lot of evidence that inflammation promotes endothelial cell differentiation. However, this activity of inflammation remains to be established in adipose tissue. The present article reviews the literature in support of this conclusion.
Distribution and Growth of Aerobic Anoxygenic Phototrophs in the Mediterranean Sea
Authors: Hojerová Eva , Mašín Michal , Brunet Christophe , Ferrera Isabel , Gasol Josep M. , Koblížek Michal
Published: September 2011

The distribution of aerobic anoxygenic phototrophs (AAPs) was surveyed in various regions of the Mediterranean Sea in spring and summer. These phototrophic bacteria were present within the euphotic layer at all sampled stations. The AAP abundances increased with increasing trophic status ranging from 2.5 × 103 cells per ml in oligotrophic Eastern Mediterranean up to 90 × 103 cells per ml in the Bay of Villefranche. Aerobic anoxygenic phototrophs made up on average 1–4% of total prokaryotes in low nutrient areas, whereas in coastal and more productive stations these organisms represented 3–11% of total prokaryotes. Diel bacteriochlorophyll a decay measurements showed that AAP community in the Western Mediterranean grew rapidly, at rates from 1.13 to 1.42 day−1. The lower AAP abundances registered in the most oligotrophic waters suggest that they are relatively poor competitors under nutrient limiting conditions. Instead, AAPs appear to be metabolically active organisms, which thrive better in more eutrophic environments providing the necessary substrates to maintain high growth rates.
Resistance, resilience and recovery: aquatic bacterial dynamics after water column disturbance
Authors: Shade Ashley , Read Jordan S. , Welkie David G. , Kratz Timothy K. , Wu Chin H. , McMahon Katherine D.
Published: September 2011

For lake microbes, water column mixing acts as a disturbance because it homogenizes thermal and chemical gradients known to define the distributions of microbial taxa. Our first objective was to isolate hypothesized drivers of lake bacterial response to water column mixing. To accomplish this, we designed an enclosure experiment with three treatments to independently test key biogeochemical changes induced by mixing: oxygen addition to the hypolimnion, nutrient addition to the epilimnion, and full water column mixing. We used molecular fingerprinting to observe bacterial community dynamics in the treatment and control enclosures, and in ambient lake water. We found that oxygen and nutrient amendments simulated the physical‐chemical water column environment following mixing and resulted in similar bacterial communities to the mixing treatment, affirming that these were important drivers of community change. These results demonstrate that specific environmental changes can replicate broad disturbance effects on microbial communities. Our second objective was to characterize bacterial community stability by quantifying community resistance, recovery and resilience to an episodic disturbance. The communities in the nutrient and oxygen amendments changed quickly (had low resistance), but generally matched the control composition by the 10th day after treatment, exhibiting resilience. These results imply that aquatic bacterial assemblages are generally stable in the face of disturbance.
Your patient information website: how good is it?
Authors: Soobrah R. , Clark S. K.
Published: September 2011

Aim  The study was designed to evaluate the accessibility, reliability and readability of information on familial adenomatous polyposis (FAP) on the Web.

Method  We searched for the keywords ‘familial adenomatous polyposis’ using the three most popular search engines (Google™ Yahoo™, MSN™) and looked at the first 50 websites. The LIDA tool (an online validation instrument for healthcare websites) was used to assess their accessibility, usability and reliability. The readability of each document was assessed using the Flesch Reading Ease (FRE) score. We also checked whether each site was certified by the Health on the Net Foundation Code of Conduct (HONcode) – the oldest and most trustworthy code for medical and health‐related information available on the Internet.

Results  Of the 150 possible sites, only 48 were analysed because of repetitions (52), irrelevant content (21) or inaccessible links (29). Nineteen were HONcode‐certified. The mean LIDA and FRE scores for all websites were 62.59% (SD = 10) and 32.9 (SD = 16) respectively. HONcode‐certified websites have slightly higher reliability scores than HONcode‐uncertified websites (38.5%vs 36.2%).

Conclusion  Good quality information on patients with FAP is difficult to obtain on the Internet. The websites analysed have alarmingly low reliability scores. The readability of their content is poor and they often do not appear among the top search results. There is a need to develop a clear, easily accessible and authoritative resource for patients with FAP.
Timing of rectosigmoid resection for diverticular disease: the patient’s view
Authors: Käser S. A. , Glauser P. M. , Basilicata G. , Müller D. A. , Maurer C. A.
Published: September 2011

Aim  The study aimed to determine the patient’s view on the timing of elective resection for sigmoid diverticulitis.

Method  A questionnaire was answered by 162 (69%) of 236 consecutive patients who had a resection of the rectosigmoid for diverticulitis from July 2002 to August 2005. Patients (n = 45) having resection at or after the first inflammatory attack were excluded, leaving 117 eligible for analysis. Questions asked included those concerning symptoms before surgery, improvement of symptoms after surgery and the timing of surgery.

Results  Patient assessment of symptoms after surgery was as follows: no improvement (2%; n = 2), some improvement (10%; n = 12), marked improvement (34%; n = 39) and complete resolution (54%; n = 63). Forty‐five (38%) patients would have preferred an earlier operation. Preference for earlier surgery related to the number of previous inflammatory attacks was expressed as follows: 13 (34%) of 38 patients after two inflammatory attacks, 5 (18%) of 28 patients after three, seven (37%) of 19 patients after four, four (44%) of nine patients after five, and 16 (70%) of 23 patients after six or more inflammatory attacks would have preferred earlier surgery. Statistically significant factors influencing this potential choice were number of episodes of pain (P = 0.006, OR = 1.23, 95% CI: 1.060–1.430) and number of attacks of inflammation (P = 0.048, OR = 1.27, 95% CI: 1.002–1.598).

Conclusion  Surgery for recurrent diverticulitis resulted in a marked improvement or complete relief of symptoms in 88% of patients. A large proportion of patients with recurrent episodes of sigmoid diverticulitis would have preferred earlier resection.
Miscoding, misclassification and misdiagnosis of diabetes in primary care
Authors: de Lusignan S. , Sadek N. , Mulnier H. , Tahir A. , Russell‐Jones D. , Khunti K.
Published: September 2011

Diabet. Med. 29, 181–189 (2012)

Aims  To determine the effectiveness of self‐audit tools designed to detect miscoding, misclassification and misdiagnosis of diabetes in primary care.

Methods  We developed six searches to identify people with diabetes with potential classification errors. The search results were automatically ranked from most to least likely to have an underlying problem. Eight practices with a combined population of 72 000 and diabetes prevalence 2.9% (n = 2340) completed audit forms to verify whether additional information within the patients’ medical record confirmed or refuted the problems identified.

Results  The searches identified 347 records, mean 42 per practice. Pre‐audit 20% (n = 69) had Type 1 diabetes, 70% (n = 241) had Type 2 diabetes, 9% (n = 30) had vague codes that were hard to classify, 2% (n = 6) were not coded and one person was labelled as having gestational diabetes. Of records, 39.2% (n = 136) had important errors: 10% (n = 35) had coding errors; 12.1% (42) were misclassified; and 17.0% (59) misdiagnosed as having diabetes. Thirty‐two per cent (n = 22) of people with Type 2 diabetes (n = 69) were misclassified as having Type 1 diabetes; 20% (n = 48) of people with Type 2 diabetes (n = 241) did not have diabetes; of the 30 patients with vague diagnostic terms, 50% had Type 2 diabetes, 20% had Type 1 diabetes and 20% did not have diabetes. Examples of misdiagnosis were found in all practices, misclassification in seven and miscoding in six.

Conclusions  Volunteer practices successfully used these self‐audit tools. Approximately 40% of patients identified by computer searches (5.8% of people with diabetes) had errors; misdiagnosis is commonest, misclassification may affect treatment options and miscoding in omission from disease registers and the potential for reduced quality of care.