bluuebunny/crossref_metadata_2025 huggingface dataset:
InterPred: A pipeline to identify and model protein-protein interactions
Authors: Mirabello Claudio , Wallner Björn
Published: October 2016

Protein-protein interactions (PPI) are crucial for protein function. There exist many techniques to identify PPIs experimentally, but to determine the interactions in molecular detail is still difficult and very time-consuming. The fact that the number of PPIs is vastly larger than the number of individual proteins makes it practically impossible to characterize all interactions experimentally. Computational approaches that can bridge this gap and predict PPIs and model the interactions in molecular detail are greatly needed. Here we present InterPred, a fully automated pipeline that predicts and model PPIs from sequence using structural modelling combined with massive structural comparisons and molecular docking. A key component of the method is the use of a novel random forest classifier that integrate several structural features to distinguish correct from incorrect protein-protein interaction models. We show that InterPred represents a major improvement in protein-protein interaction detection with a performance comparable or better than experimental high-throughput techniques. We also show that our full-atom protein-protein complex modelling pipeline performs better than state of the art protein docking methods on a standard benchmark set. In addition, InterPred was also one of the top predictors in the latest CAPRI37 experiment.

InterPred source code can be downloaded fromhttp://wallnerlab.org/InterPred
Topological features of gene regulatory networks predict patterns of natural diversity in environmental response
Authors: Des Marais David L. , Guerrero Rafael F. , Lasky Jesse R. , Scarpino Samuel V.
Published: October 2016

Molecular interactions affect the evolution of complex traits. For instance, adaptation may be constrained by pleiotropic or epistatic effects, both of which will be reflected in the structure of molecular interaction networks. To date, empirical studies investigating the role of molecular interactions in phenotypic evolution have been idiosyncratic, offering no clear patterns. Here, we investigated the network topology of genes putatively involved in local adaptation to two abiotic stressors—drought and cold—inArabidopsis thaliana. Our findings suggest that the gene-interaction topologies for both cold and drought stress response are non-random, with genes that show genetic variation in drought response (GxE) being significantly more peripheral and cold response genes being significantly more central than genes not involved in either response. We suggest that the observed topologies reflect different constraints on the genetic pathways involved in the assayed phenotypes. The approach presented here may inform predictive models linking genetic variation in molecular signaling networks with phenotypic variation, specifically traits involved in environmental response.

Significance Statement

Our study focuses on genes whose transcriptional activity exhibits genetic variation in response to the environment, or “GxE.” GxE is a widely observed phenomenon of critical importance to understanding the genotype-to-phenotype map, the evolution of natural populations, medical genetics, population response to climate change, and agricultural improvement. We investigated expression GxE in plant responses to two abiotic cues: cold and drought. We found that genes showing genetically variable response to cold stress are centrally located in regulatory networks whereas genes showing genetically variable response to drought stress are peripherally located in regulatory networks. This result suggests that selection is presented with vastly different mutational landscapes for shaping evolutionary or breeding response to these two important climatic factors
Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS)
Authors: Perkins Stephen J. , Wright David W. , Zhang Hailiang , Brookes Emre H. , Chen Jianhan , Irving Thomas C. , Krueger Susan , Barlow David J. , Edler Karen J. , Scott David J. , Terrill Nicholas J. , King Stephen M. , Butler Paul D. , Curtis Joseph E.
Published: October 2016

The capabilities of current computer simulations provide a unique opportunity to model small-angle scattering (SAS) data at the atomistic level, and to include other structural constraints ranging from molecular and atomistic energetics to crystallography, electron microscopy and NMR. This extends the capabilities of solution scattering and provides deeper insights into the physics and chemistry of the systems studied. Realizing this potential, however, requires integrating the experimental data with a new generation of modelling software. To achieve this, the CCP-SAS collaboration (http://www.ccpsas.org/) is developing open-source, high-throughput and user-friendly software for the atomistic and coarse-grained molecular modelling of scattering data. Robust state-of-the-art molecular simulation engines and molecular dynamics and Monte Carlo force fields provide constraints to the solution structure inferred from the small-angle scattering data, which incorporates the known physical chemistry of the system. The implementation of this software suite involves a tiered approach in which GenApp provides the deployment infrastructure for running applications on both standard and high-performance computing hardware, and SASSIE provides a workflow framework into which modules can be plugged to prepare structures, carry out simulations, calculate theoretical scattering data and compare results with experimental data. GenApp produces the accessible web-based front end termed SASSIE-web, and GenApp and SASSIE also make community SAS codes available. Applications are illustrated by case studies: (i) inter-domain flexibility in two- to six-domain proteins as exemplified by HIV-1 Gag, MASP and ubiquitin; (ii) the hinge conformation in human IgG2 and IgA1 antibodies; (iii) the complex formed between a hexameric protein Hfq and mRNA; and (iv) synthetic `bottlebrush' polymers.
ShadowOui: a new visual environment for X-ray optics and synchrotron beamline simulations
Authors: Rebuffi Luca , Sánchez del Río Manuel
Published: October 2016

A new computer environment to perform simulations on synchrotron experiments has been designed. It performs ray-tracing simulations using the popular ray-tracing codeSHADOW. With this new application one can define, in a very easy and elegant way, one or several optical systems (beamlines) and perform calculations of the propagation of the X-ray beam through it. Many complementary tools and supplementary calculations improve and extend the functionality ofSHADOWto deal with complex optical system optimization, including compound optical elements, iterative calculations, some sample simulations, and implementing corrections for wave opticsviaa hybrid model.
XDS: a flexible beamline for X-ray diffraction and spectroscopy at the Brazilian synchrotron
Authors: Lima F. A. , Saleta M. E. , Pagliuca R. J. S. , Eleotério M. A. , Reis R. D. , Fonseca Júnior J. , Meyer B. , Bittar E. M. , Souza-Neto N. M. , Granado E.
Published: October 2016

The majority of the beamlines at the Brazilian Synchrotron Light Source Laboratory (LNLS) use radiation produced in the storage-ring bending magnets and are therefore currently limited in the flux that can be used in the harder part of the X-ray spectrum (above ∼10 keV). A 4 T superconducting multipolar wiggler (SCW) was recently installed at LNLS in order to improve the photon flux above 10 keV and fulfill the demands set by the materials science community. A new multi-purpose beamline was then installed at the LNLS using the SCW as a photon source. The XDS is a flexible beamline operating in the energy range between 5 and 30 keV, designed to perform experiments using absorption, diffraction and scattering techniques. Most of the work performed at the XDS beamline concentrates on X-ray absorption spectroscopy at energies above 18 keV and high-resolution diffraction experiments. More recently, new setups and photon-hungry experiments such as total X-ray scattering, X-ray diffraction under high pressures, resonant X-ray emission spectroscopy, among others, have started to become routine at XDS. Here, the XDS beamline characteristics, performance and a few new experimental possibilities are described.
Lytic polysaccharide monooxygenases: a crystallographer's view on a new class of biomass-degrading enzymes
Authors: Frandsen Kristian E. H. , Lo Leggio Leila
Published: October 2016

Lytic polysaccharide monooxygenases (LPMOs) are a new class of microbial copper enzymes involved in the degradation of recalcitrant polysaccharides. They have only been discovered and characterized in the last 5–10 years and have stimulated strong interest both in biotechnology and in bioinorganic chemistry. In biotechnology, the hope is that these enzymes will finally help to make enzymatic biomass conversion, especially of lignocellulosic plant waste, economically attractive. Here, the role of LPMOs is likely to be in attacking bonds that are not accessible to other enzymes. LPMOs have attracted enormous interest since their discovery. The emphasis in this review is on the past and present contribution of crystallographic studies as a guide to functional understanding, with a final look towards the future.
Crystal structure of (nitrato-κO)bis(1,10′-phenanthroline-κ2
N,N′)copper(II) nitrate gallic acid monosolvate monohydrate
Authors: Shen Fwu Ming , Lush Shie Fu
Published: October 2016

The title compound, [Cu(NO3)(C12H8N2)2]NO3·C7H6O5·H2O, consists of a mononuclear complex cation with the central CuII atom in a distorted trigonal–bipyramidal coordination sphere. Two N atoms of two 1,10-phenanthroline ligands occupy the axial sites, and the remaining N atoms of the two ligands, as well as one nitrate O atom the equatorial positions. One molecule each of gallic acid and water are present in the crystal as solvent molecules that do not coordinate to the CuII cation, just as the nitrate counter-anion. In the crystal, intermolecular O—H...O hydrogen bonds, as well as C—H...O interactions and π–π ring stacking between benzene and pyridine rings [centroid-to-centroid distances = 3.471 (2), 3.559 (2) and 3.790 (2) Å], link the molecules into a three-dimensional network structure.
2,4-Dimethylpyrido[1,2-a]pyrimidin-5-ium perchlorate
Authors: Posel Maciej , Stoeckli-Evans Helen
Published: October 2016

In the title molecular salt, C10H11N2
+·ClO4
−, the pyrido[1,2-a]pyrimidin-5-ium cation is planar, with an r.m.s. deviation of 0.027 Å for all 12 non-H atoms. The perchlorate anions are distributed over two twofold rotation axes; for one, three of the O atoms are disordered over two sites (occupancies of 1/2). In the crystal, the cations are linked via C—H...N hydrogen bonds, forming chains propagating along [001]. The chains are linked by a C—H...O hydrogen bond involving the non-disordered perchlorate anion, forming double layers parallel to the bc plane. These layers are linked by a number of weak C—H...O hydrogen bonds involving the disordered perchlorate anion, forming a three-dimensional framework.
Ammonium hydrogen bis[4-(2-phenyl-2H-tetrazol-5-yl)benzoate]
Authors: Janzen Daron E. , Lange Kayla A. , Wollack James W.
Published: October 2016

The title salt, NH4
+·H+·2C14H9N4O2
−, is composed of an ammonium cation with a strong intermolecular negatively charge-assisted hydrogen-bonded acid/conjugate base-pair monoanion. The carboxylic acid H atom is located on an inversion center, while the N atom of the ammonium cation is located on a twofold rotation axis. In the crystal, the N—H bonds of each ammonium cation act as donors with carboxylate O-atom acceptors to form chains along the a-axis direction. The chains are linked by offset π–π interactions [intercentroid distances = 3.588 (2) and 3.686 (2) Å], forming layers parallel to the ab plane.
3-(4-Chlorophenyl)-4-phenylthiosydnone
Authors: Grossie David A. , Turnbull Kenneth
Published: October 2016

In the structure of C14H9ClN2O2S [systematic name: 3-(4-chlorophenyl)-4-(phenylsulfanyl)-1,2,3λ5-oxadiazol-3-ylium-5-olate], the central sydnone ring is inclined at angles of 67.49 (10)° to the phenyl ring of the thiophenyl substituent and 52.61 (10)° to the chlorophenyl ring. The compound crystallizes utilizing a network of weak S and Cl-based hydrogen bonds, together with S...π, O...π and C—H...π interactions, forming a three-dimensional structure. In spite of having three planar rings, no π–π interactions are found.
Ethyl 4,6-dimethyl-3-oxo-2-phenyl-3,7-dihydro-2H-pyrazolo[3,4-b]pyridine-5-carboxylate monohydrate
Authors: Akhramez Soufiane , Hafid Abderrafia , Khouili Mostafa , Mentre Olivier , Ketatni El Mostafa
Published: October 2016

In the title compound, C17H17N3O3·H2O, the dihedral angle between the 4,6-dimethyl-pyrazolo[3,4-b]pyridine-3-one unit [maximum deviation = 0.048 (2) Å] and the phenyl ring is 5.1 (1)°. The structure is characterized by disorder of the carboxylate O atoms, which are split into two parts with a major component of 0.898 (4). In the crystal, the organic molecules and lattice water molecules are linked via O—H...O, O—H...N and N—H...O hydrogen bonds. The molecules are also linked by C—H...π and weak offset π–π stacking interactions, forming sheets parallel to (001).
Use of an I.C.T. 1907 computer in Southampton university library Report No 2
Authors: Woods R.G.
Published: October 2016

Since the publication of the report of our work in Program No. 1, several librarians have asked to be kept informed of the progress we are making. This second report covers the period between March and September 1966, and deals with changes and developments in the issue system.
Computer applications in the fields of library housekeeping and information processing
Authors: Kimber R.T.
Published: October 2016

Computer‐aided systems for all four of the conventional divisions of the field of library housekeeping are now operational in libraries. In Great Britain the only activity not yet operational is that of periodicals control, although two libraries have already used a computer to produce lists of periodicals holdings. The aim of this paper is to describe simply how computer‐aided housekeeping systems work, from the point of view of the librarian, and to mention briefly some typical applications of each type of system.
Computers and Libraries
Authors: Dews J.David
Published: October 2016

In under twenty years the computer has developed from a laboratory toy to the sophisticated machines which are daily having a greater and greater effect on our lives. Almost every week, new equipment, improvements in existing equipment, and new ways of using the machines to make them more convenient, are being announced. A computer generation is now about five years — and that is just about the time it will take to install an automated system in a library and get it working.
Development of a machine‐readable catalogue at the University of Essex
Authors: Sommerlad M.J.
Published: October 2016

The decision to commence automation activities in the library of the University of Essex with cataloguing was based upon the very real prospect of a new library being able to avoid one of the potential problems of most other libraries. There, the conversion of a mass of existing entries must be completed before any computer‐based cataloguing system can become fully effective. The possession of a comprehensive machine‐readable catalogue record for each book will also simplify the introduction of an automated circulation system when the rapidly growing population of the University makes this necessary.
Self issue — the management implications. The introduction of self‐service at the University of Sunderland
Authors: JanetStafford
Published: October 2016

Self issue facilitates an improvement in the service for the borrower and should be considered carefully by librarians everywhere. It can help to provide the means to address the growing demands of the user whilst so many libraries suffer from the enormous pressures of limited library resources and budgetary constraints. The self issue project at Information Services, University of Sunderland, has identified preparation, publicity, position and persuasion as the four key ‘p’ elements essential for the successful implementation of the service. This paper will provide a synopsis of the methods used to achieve success, a description of self issue machine components and operational procedures. Project achievements and plans for the future are outlined.
Plant functional groups within a tropical forest exhibit different wood functional anatomy
Authors: Apgaua Deborah M. G. , Tng David Y. P. , Cernusak Lucas A. , Cheesman Alexander W. , Santos Rubens M. , Edwards Will J. , Laurance Susan G. W.
Published: October 2016

Understanding the anatomical basis of plant water transport in forest ecosystems is crucial for contextualizing community‐level adaptations to drought, especially in life‐form‐rich tropical forests. To provide this context, we explored wood functional anatomy traits related to plant hydraulic architecture across different plant functional groups in a lowland tropical rain forest.

We measured wood traits in 90 species from six functional groups (mature‐phase, understorey and pioneer trees; understorey and pioneer shrubs; vines) and related these traits to intrinsic water‐use efficiency (WUEi) as a measure of physiological performance. We also examined vessel size distribution patterns across groups to determine trade‐offs in theoretical hydraulic safety vs. efficiency.

Some plant functional groups exhibited significant differences in vessel parameters and WUEi. Vessel diameters in vines and pioneer trees were two‐ to threefold greater on average than in understorey trees and shrubs. Contrastingly, vessels in understorey trees and shrubs fell within the smaller size classes, suggesting greater safety mechanisms. In addition to these trends, large vessel dimensions were important predictors of WUEi among the functional groups.

We conclude that wood functional anatomy profiles varied across plant functional groups in a tropical rain forest. These groups can therefore serve as a framework for further investigations on structure–function relationships and a sound basis for modelling species responses to drought.

A lay summary is available for this article.
Not a German past to be reckoned with: negotiating migrant subjectivities between Vergangenheitsbewältigung and the nationalization of history
Authors: von Bieberstein Alice
Published: October 2016

In discussing the public commemoration of the Armenian genocide and the case of a Turkish refugee‐turned‐memory‐activist in Germany, this article focuses on migrants as they mediate political concerns by reference to the German discourse and practice of Vergangenheitsbewältigung (confronting the past). Such engagements shed light on the intersection of a performative and inclusionary dimension of citizenship inscribed in the figure of the repentant perpetrator and the continuous re‐ethnicization of subjects by reference to particular nationalized histories. The analysis thus reveals the ‘memorial’ contour of a normative German citizen‐subject, one that is self‐reflexive vis‐à‐vis his or her national past. The article charts how the politics of history and citizenship thus play out at the level of subjectivity, implicating registers of affect and aesthetics that are not captured by the more commonly employed framework of ‘memory’, which falls short of analytical import precisely because it lacks a theory of the subject.
Cluster validity and uncertainty assessment for self‐organizing map pest profile analysis
Authors: Roigé Mariona , McGeoch Melodie A. , Hui Cang , Worner Susan P.
Published: October 2016

Pest risk assessment (PRA) comprises a set of quantitative and qualitative tools to protect productive ecosystems from the impacts of unwanted biological invasions.

Self‐organizing maps for pest profile analysis (SOM PPA) is a methodological approach aimed to support PRA. It is based on cluster analysis and extracts information out of current distributions of insect crop pests world‐wide, allowing the analyst to generate a list of potential risk species for a target region.

Self‐organizing maps for pest profile analysis currently lacks of a measure of performance able to provide a level of confidence for its outputs.

In this study, we investigate ζ diversity as an ecologically meaningful and generalizable metric of similarity. The application of ζ allowed us to quantify and thus reveal different levels of similarity across pest profiles.

The use of ζ diversity applied to the SOM PPA provides an informative measure of uncertainty for the output of SOM PPA, thus adding major improvements to the methodology while only marginally increasing its complexity.
Protein and RNA extraction from mucosal swabs: a minimally invasive source of ecological data for studies of natural populations
Authors: Espinosa‐de Aquino Wendy , Olvera‐Ramírez Andrea , Arellano‐Carbajal Fausto , Lanz‐Mendoza Humberto , Villagrán‐Herrera Elena , Acevedo‐Whitehouse Karina
Published: October 2016

Mucosal swabs have long been used to study various physiological processes in humans. In contrast, systematic sampling of mucosae is rare for wild animals, and except for its use as a source of DNA for population genetics, its potential as a tool to study physiologically relevant processes of natural populations has not been explored fully.

We collected swabs from the rectal, genital, nasal and oral mucosae of California sea lion pups and investigated differences in RNA and protein yield, quality and integrity between storage times and mucosal types. Downstream applications were tested on the extracted products to determine the potential value of mucosal sampling in free‐ranging mammals.

For most samples, RNA yield was stable regardless of storage time, and RNA quality and integrity were equal for all mucosal types. Ribosomal fragments of sizes expected for mammals, yeast and bacteria were observable in genital and rectal samples, but in nasal and oral samples only bacterial ribosomal fragments were observable. Amplification of selected transcripts was successful for all samples. The protein profile was distinct between mucosae, and samples with high protein yields were useful for antibody detection.

Our study demonstrates that mucosal swabbing is a minimally invasive tool that yields useful physiological data for free‐ranging wildlife. Minimum experience is needed to collect samples, processing is inexpensive, and downstream applications for ecological studies are realistic.
Do never smokers make up an increasing share of snus users as cigarette smoking declines? Changes in smoking status among male snus users in Norway 2003–15
Authors: Lund Karl Erik , Vedøy Tord Finne , Bauld Linda
Published: October 2016

Aims

To examine how the relative size of six groups of male ever snus users (current and former users of snus who were current, former or never cigarette smokers) varied over time in Norway, and how these groups differ with regard to important measures of tobacco behaviour.

Design

Repeated cross‐sectional nationally representative surveys of tobacco use. The association between survey year and the six categories of ever snus use was examined using cross‐tabulation and multinomial logistic regression. Differences in tobacco behaviour across snus use categories were examined using logistic and ordinary least squares (OLS) regression.

Setting

Norway, 2003–15.

Participants

A total of 2067 males aged 15–79 years.

Measurements

The categories of ever snus use represented all six combinations of cigarette smoking (current, former or never) among current and former users of snus. The variables measuring tobacco behaviour were: order of product uptake (snus or cigarettes first), mean cigarette consumption, reduction from daily to occasional smoking, intention to quit cigarettes, future smoking identity and use of snus in latest quit attempt.

Findings

During the period 2003–15, the relative share of current snus users who had never smoked, and current snus users who were former smokers, increased. The share of dual users, and smokers who were former snus users, decreased. Among men who reported life‐time experience with both products, a large majority had initiated their tobacco use with cigarettes. The average number of cigarettes smoked weekly was lower among dual users compared with current smokers who were former snus users or had never used snus.

Conclusions

During the period 2003–15 in Norway, which has a mature snus market, even though smoking has declined and the relative size of the category of never‐smokers among male users of snus has increased, the majority of snus users are still former or current smokers.
The role of leaf cellulose content in determining host plant preferences of three defoliating insects present in the Andean‐Patagonian forest
Authors: Pietrantuono A. L. , Bruzzone O. A. , Fernández‐Arhex V.
Published: October 2016

Phytophagous insects choose their feeding resources according to their own requirements in addition to properties of the host plants, such as biomechanical defences. The feeding preferences of the native folivorous insects of the Andean‐Patagonian forest (Argentina) have rarely been studied. These environments present a wide diversity and abundance of insects associated with trees of the Nothofagus and Lophozonia (Nothofagaceae) genera, which represent the main tree species of the forests of the southern hemisphere. In particular, Lophozonia alpina and Lophozonia obliqua are of great interest because they have a wide distribution, a high capacity for hybridization and exhibit great phenotypic plasticity. This versatility causes substantial variation in the biomechanical properties of leaves, affecting the feeding preferences of insects. The purpose of this work was to study the food selection behaviour of three leaf‐chewing insects (Polydrusus nothofagii, Polydrusus roseaus (Coleoptera: Curculionidae) and Perzelia arda (Lepidoptera: Oecophoridae)) associated with L. alpina and L. obliqua as host plants. Based on their choices, our aim was to determine a preference scale for each insect species and the variables on which these preferences were based. Therefore, we selected trees of L. alpina and L. obliqua, measured several properties such as cellulose content and recorded which leaves were eaten. As a result, we determined that the three species of insects feed on both host plants but prefer the leaves of L. obliqua, with cellulose content being the main determining factor for their decisions. However, in the case of P. arda, there was a positive relationship between cellulose and host plant preference, whereas there was an opposite relationship for the weevils. We conclude that during feeding selection, there are some properties of the leaves that have a more important role than others and that the same property does not exert the same behavioural response in all folivorous insects.
Endometriosis and uterine malformations: infertility may increase severity of endometriosis
Authors: Boujenah Jeremy , Salakos Eleonora , Pinto Mélodie , Shore Joanna , Sifer Christophe , Poncelet Christophe , Bricou Alexandre
Published: October 2016

Introduction

The aim of our study was to compare the stage and severity of endometriosis in fertile and infertile women with congenital uterine malformations.

Material and methods

We performed an observational study from September 2007 to December 2015 in a tertiary care university hospital and assisted reproductive technology center. A total of 52 patients with surgically proven uterine malformations were included. We compared 41 infertile patients with uterine malformations with 11 fertile patients with uterine malformation. The main outcome was the stage, score and type of endometriosis in regard to infertility and class of uterine malformation.

Results

The rate of endometriosis did not differ between the two groups (43.9 vs. 36.4%). The mean revised American Fertility Society score was higher in infertile patients with uterine malformations (19.02 vs. 6, p < 0.05). No significant difference was found in the rate of superficial peritoneal endometriosis (43.9 vs. 37.5%). Endometrioma and deep infiltrating endometriosis were associated with uterine malformations in infertile women, respectively 14.6 and 0%. No difference in the characteristics of endometriosis was found regarding the class of malformation.

Conclusions

The association of uterine malformations and infertility may increase the severity of endometriosis and raise the issue of their diagnosis and management.
Spallation of Small Particles From Peristaltic Pump Tube Segments
Authors: Liu Yi , Faria Monica , Leonard Edward
Published: October 2016

In most extracorporeal filtration devices such as hemodialysis a peristaltic pump is used to circulate blood. Pump function requires the repeated compression of an elastomeric tube from which particles may be shed into the circulatory system, a process called spallation. Earlier studies are likely to have missed the large number of small particles (<2 µm in diameter) that appear. The present study uses more modern equipment that detects and sizes particles down to 0.6 µm. As polyvinyl chloride (PVC) tubing is commonly used for this process, a series of studies was conducted on three different types to study its spallation characteristics, along with a co‐extruded PVC/polyurethane tubing known for its enhanced biocompatibility properties. For all types of PVC tubes, the average size of the spallated particles was 0.83 ± 0.03 µm; for the PVC/polyurethane tubing the average size of the spallated particles was approximately twice that reported for PVC tubing. For PVC tubes with equal inner diameter, those with less plasticizer released fewer particles; for tubes with the same Shore hardness, tubes with larger internal diameters released fewer particles. It was also shown that PVC tubes operating at a slower flow rate does not reduce the total number of particles released per volume pumped. The total number of particles spallated from the PVC/polyurethane tubing was 10 times lower than from the lowest spallating PVC tubing.
Is it possible to cure childhood acute myeloid leukaemia without significant cardiotoxicity?
Authors: Jarfelt Marianne , Andersen Niels H. , Hasle Henrik
Published: October 2016

Since cardiotoxicity is a life threatening late effect, a reduction of cardiotoxicity in the treatment of acute myeloid leukaemia (AML) is essential. This review is a compilation of the current knowledge about cardiotoxicity after AML treatment and of how future directions in treatment may affect its incidence. A total of six studies concerning AML and cardiotoxicity were identified. The incidence of late subclinical cardiotoxicity varied between 1·3 and 15·3%, and late clinical cardiotoxicity varied between 1·3 and 9·3%. Cumulative dose of anthracyclines (ACs) and history of relapse were the most common risk factors identified. No conclusions could be drawn about new, potentially less toxic ACs. Differences in treatment data and variations in study populations made comparisons uncertain. The echocardiographic techniques used in the majority of the studies are inferior to more modern echocardiographic methods. This decreases reproducibility and may increase the risk of overestimation of cardiotoxicity. In summary, AML cannot be cured today without ACs. However, some ACs may cause less cardiotoxicity than others. Furthermore there is currently no consensus on equipotent doses of ACs and risk factors for cardiotoxicity. Further research including randomized trials is needed to evaluate whether or not the potentially less cardiotoxic agents fulfil their promise.
Diffuse large B‐cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era
Authors: Kridel Robert , Telio David , Villa Diego , Sehn Laurie H. , Gerrie Alina S. , Shenkier Tamara , Klasa Richard , Slack Graham W. , Tan King , Gascoyne Randy D. , Connors Joseph M. , Savage Kerry J.
Published: October 2016

The addition of rituximab has improved outcomes in diffuse large B‐cell lymphoma (DLBCL), however, there remains limited information on the impact of rituximab in those with testicular involvement. All patients with diffuse large cell lymphoma and testicular involvement treated with curative intent were identified in the British Columbia Cancer Agency Lymphoid Cancer Database. In total, 134 patients diagnosed between 1982 and 2015 with diffuse large cell lymphoma involving the testis were identified: 61 received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)‐like chemotherapy and 73 received CHOP plus rituximab (R‐CHOP). A greater proportion of R‐CHOP treated patients had higher International Prognostic Index (IPI, P = 0·005). In multivariate analysis, the protective effect of rituximab on progression‐free survival (hazard ratio (HR) 0·42, P < 0·001), overall survival (HR 0·39, P < 0·001) and cumulative incidence of progression (HR 0·46, P = 0·014) were independent of the IPI. However, in a competing risk multivariate analysis including central nervous system (CNS) prophylaxis and the CNS‐IPI, rituximab was not associated with a decreased risk of CNS relapse. The addition of rituximab has reduced the risk of lymphoma recurrence in testicular DLBCL, presumably through improved eradication of systemic disease. However, CNS relapse risk remains high and further studies evaluating effective prophylactic strategies are needed.
Participation of Australian Aboriginal and Torres Strait Islander families in a parent support programme: longitudinal associations between playgroup attendance and child, parent and community outcomes
Authors: Williams K. E. , Berthelsen D. , Viviani M. , Nicholson J. M.
Published: October 2016

Background

Playgroups are a relatively unique form of family support programme that is common in Australia which has high community acceptance and significant government investment. However, limited evidence exists regarding the effectiveness of playgroups to achieve better outcomes for children and their parents. This study describes patterns of playgroup participation for Aboriginal and Torres Strait Islander families with young children and examines the extent to which participation from birth to three years is associated with subsequent child, parent and community outcomes.

Methods

This study uses three years of longitudinal data for 622 Aboriginal and Torres Strait Islander children who were participants in the Longitudinal Study of Indigenous Children (LSIC). Longitudinal associations between playgroup attendance when children were age 2 and 3 years and outcome measures for child vocabulary, motor skills, behaviour problems, prosocial development, parent home learning engagement, resilience, advice‐seeking and health service use, and community trustworthiness were examined using path analysis.

Results

Rates of playgroup participation in this sample group were generally lower than for Australian children overall. Playgroup attendance when children were age 2 to 3 years was associated with higher parental engagement in home learning activities when children were aged 4 years which, in turn, was associated with stronger expressive vocabulary scores for children.

Conclusion

The findings from this study suggest that playgroup participation can enhance the home learning environments for Aboriginal and Torres Strait Islander children. Playgroups as a parent support programme hold strong potential to reach and engage families, particularly in areas of high geographic isolation, which can realize improved outcomes for children, parents and communities.
LABOR SUPPLY ESTIMATION BIASES FROM DISREGARDING NONWAGE BENEFITS
Authors: Baird Matthew D.
Published: October 2016

Labor supply models and research underpinned by labor supply decisions often assume that workers' choices are functions of wage and wage offers. However, the literature shows evidence that such decisions at least partly depend on nonwage benefits encompassed in jobs and occupations. In this paper, I develop and estimate a stochastic dynamic model of occupation and job choice, where nonwage benefits are directly incorporated into the decision alongside wages (a full model). Nested within the full model is a wage model, which represents the common practice in the literature of basing selection solely on wages and disregarding nonwage benefits. I separately estimate the full model and the nested wage model to compare the implications (biases) of omitting nonwage benefits. I compare the two models' estimates of elasticities and an inequality reduction intervention policy. I find that disregarding nonwage benefits generally causes biases. There are cases when the two models predict very similar outcomes and have close estimates, such as in occupation‐specific elasticities and job transition elasticities. But these special cases are products of canceling biases. In most cases, ignoring nonwage benefits will bias estimates by overestimating the importance of wage in the selection process and by disregarding changes in relative prices between wage and nonwage benefits. (JEL J20, J32, D91)
Dorsal root ganglion axon bifurcation tolerates increased cyclic GMP levels: the role of phosphodiesterase 2A and scavenger receptor Npr3
Authors: Schmidt Hannes , Peters Stefanie , Frank Katharina , Wen Lai , Feil Robert , Rathjen Fritz G.
Published: October 2016

A cyclic GMP (cGMP) signaling pathway, comprising C‐type natriuretic peptide (CNP), its guanylate cyclase receptor Npr2, and cGMP‐dependent protein kinase I, is critical for the bifurcation of dorsal root ganglion (DRG) and cranial sensory ganglion axons when entering the mouse spinal cord and the hindbrain respectively. However, the identity and functional relevance of phosphodiesterases (PDEs) that degrade cGMP in DRG neurons are not completely understood. Here, we asked whether regulation of the intracellular cGMP concentration by PDEs modulates the branching of sensory axons. Real‐time imaging of cGMP with a genetically encoded fluorescent cGMP sensor, RT‐PCR screens, in situ hybridization, and immunohistology combined with the analysis of mutant mice identified PDE2A as the major enzyme for the degradation of CNP‐induced cGMP in embryonic DRG neurons. Tracking of PDE2A‐deficient DRG sensory axons in conjunction with cGMP measurements indicated that axon bifurcation tolerates increased cGMP concentrations. As we found that the natriuretic peptide scavenger receptor Npr3 is expressed by cells associated with dorsal roots but not in DRG neurons itself at early developmental stages, we analyzed axonal branching in the absence of Npr3. In Npr3‐deficient mice, the majority of sensory axons showed normal bifurcation, but a small population of axons (13%) was unable to form T‐like branches and generated turns in rostral or caudal directions only. Taken together, this study shows that sensory axon bifurcation is insensitive to increases of CNP‐induced cGMP levels and Npr3 does not have an important scavenging function in this axonal system.
2‐Deoxy‐d‐glucose enhances tonic inhibition through the neurosteroid‐mediated activation of extrasynaptic GABAA receptors
Authors: Forte Nicola , Medrihan Lucian , Cappetti Beatrice , Baldelli Pietro , Benfenati Fabio
Published: October 2016

Objective

The inhibition of glycolysis exerts potent antiseizure effects, as demonstrated by the efficacy of ketogenic and low‐glucose/nonketogenic diets in the treatment of drug‐resistant epilepsy. ATP‐sensitive potassium (KATP) channels have been initially identified as the main determinant of the reduction of neuronal hyperexcitability. However, a plethora of other mechanisms have been proposed. Herein, we report the ability of 2‐deoxy‐d‐glucose (2‐DG), a glucose analog that inhibits glycolytic enzymes, of potentiating γ‐aminobutyric acid (GABA)ergic tonic inhibition via neurosteroid‐mediated activation of extrasynaptic GABAA receptors.

Methods

Acute effects of 2‐DG on the ATP‐sensitive potassium currents, GABAergic tonic inhibition, firing activity, and interictal events were assessed in hippocampal slices by whole‐cell patch‐clamp and local field potential recordings of dentate gyrus granule cells.

Results

Acute application of 2‐DG activates two distinct outward conductances: a KATP channel–mediated current and a bicuculline‐sensitive tonic current. The effect of 2‐DG on such GABAergic tonic currents was fully prevented by either finasteride or PK11195, which are specific inhibitors of the neurosteroidogenesis pathway acting via different mechanisms. Moreover, the oxidized form of vitamin C, dehydroascorbic acid, known for its ability to induce neurosteroidogenesis, also activated a bicuculline‐sensitive tonic current in a manner indistinguishable from that of 2‐DG. Finally, we found that the enhancement of KATP current by 2‐DG primarily regulates intrinsic firing rate of granule cells, whereas the increase of the GABAergic tonic current plays a key role in reducing the frequency of interictal events evoked by treatment of hippocampal slices with the convulsive agent 4‐aminopyridine.

Significance

We demonstrated, for the first time, that 2‐DG potentiates the extrasynaptic tonic GABAergic current through activation of neurosteroidogenesis. Such tonic inhibition represents the main conductance responsible for the antiseizure action of this glycolytic inhibitor.
Fatigue remaining life estimation for remanufacturing truck crane Jib structure based on random load spectrum
Authors: Dong Q. , Xu G.N. , Ren H.L. , Wang A.H.
Published: October 2016

For remanufacturing truck cranes with the characteristic of single piece production, the coupling effect of multi‐physical fields and the correlation of multi‐defect modes are also faced in service. This causes that the safety of crane jib structures has great volatility and uncertainty and is difficult to be judged by fatigue test and damage test. To solve the above problems, an approach of fatigue remaining life evaluation based on random load spectrum is presented. By collecting operating cycle times corresponding to characteristic parameter values during the given time period, the small‐sample measured load spectrum is acquired. Six probability distribution models are used to fit the lifting weight sample in characteristic parameters and the optimal distribution model based on Akaike's information criterion (AIC) is obtained. With the Latin hypercube sampling (LHS) method, a random sample of lifting weight is determined within the fixed inspection cycle. In addition, combining with the rated lifting weight table of truck crane, the corresponding jib length and working range are confirmed. Through defining random values of character parameters and matched operating cycle times, a random load spectrum is gained, thus enabling the extension of measured load spectrum. Depending on the remanufacturing information database, the remanufacturing information of truck crane are retrieved to determine fatigue dangerous cross sections and critical points of jib structures. In order to reflect the variation of structure stress level, the equivalent cross sections of dangerous cross sections are constructed. The first principal stress–time history simulation model for critical points is established, and the rain‐flow counting technology is adopted to extract the two‐dimensional stress spectrum from simulation results. Using the Paris formula combined with the greatest risk principle, the fatigue residual life of jib structure is estimated. Furthermore, the fatigue remaining life evaluation system for jib structure of remanufacturing truck crane is developed for easier application of the proposed method. Finally, as an illustrative example, jib structures of ZLJ5551JQZ110V remanufacturing truck crane are provided to demonstrate the validity and feasibility of this method and system.
Phylogeographic analysis of invasive Asian earthworms (Amynthas) in the northeast United States
Authors: Schult Nancy , Pittenger Kelly , Davalos Sam , McHugh Damhnait
Published: October 2016

Phylogeographic studies are useful in reconstructing the history of species invasions, and in some instances can elucidate cryptic diversity of invading taxa. This can help in predicting or managing the spread of invasive species. Among terrestrial invasive species in North America, earthworms can have profound ecological effects. We are familiar with the centuries‐old invasions of European earthworms (Lumbricidae) and their impacts on nutrient cycling in soils. More recent invasions by Asian earthworms of the family Megascolecidae are less fully understood. We used data for two mitochondrial gene fragments, cytochrome oxidase I (COI) and 16S rRNA, to examine the relationships among populations of Asian earthworms in the megascolecid genus Amynthas in the northeast United States. Recent reports have indicated that one species in particular, Amynthas agrestis, is having detrimental effects in mixed forest ecosystems, and we were interested in understanding the invasion history for this species. We were surprised to discover three divergent mitochondrial lineages of Amynthas occurring sympatrically in upstate New York. Given the gap between intra‐ and inter‐lineage sequence divergences, we propose that these three lineages represent cryptic species of Amynthas, one of which is A. agrestis. For each of the three lineages of Amynthas, we observed shared haplotypes across broad geographic distances. This may reflect common origins for populations in each lineage, either by direct routes from native ranges or through post‐introduction spread by natural dispersal or human‐mediated transport within North America. Management efforts focused on horticultural imports from Asia, commercial nurseries within the USA, and on prohibition of bait disposal may help to reduce the further invasion success of Amynthas.
Asynchronous diversification of snakes in the North American warm deserts
Authors: Myers Edward A. , Hickerson Michael J. , Burbrink Frank T.
Published: October 2016

Aim

We quantify the degree to which co‐distributed snakes across the Cochise Filter Barrier (CFB) have a shared history of population divergence and estimate the timing of divergence for each taxon pair.

Location

North America.

Methods

A single locus dataset was collected (n = 747 individuals) for 12 snake taxon pairs. Phylogeographical structure was estimated for each taxon. Redundancy analyses were used to assess the importance of geographical distance, climate and putative barriers to gene flow in structuring genetic diversity. Hierarchical approximate Bayesian computation was used to estimate the magnitude of synchronicity in divergence times across a well‐documented phylogeographical barrier. Lastly, gene divergence and population divergence times were estimated using multiple methods.

Results

There is substantial phylogeographical structure in many of the snake taxa, particularly at the CFB. A model containing distance, climate and barriers explained the greatest amount of genetic variation in nearly all taxa. When each variable was examined separately, climate explained the most variation. The hABC model testing indicates that there is overwhelming support for asynchronous phylogeographical histories within these co‐distributed taxa. Estimated divergence times range throughout the Quaternary and Neogene.

Main Conclusions

We demonstrate that the 12 snake taxon pairs studied here have diversified within the desert Southwest forming distinct Sonoran and Chihuahuan populations, illustrating the importance of this region in driving diversification in North American taxa. Although these groups exhibit the same pattern of lineage formation, there is strong support for asynchronous diversification and little concordance in divergence time estimates.