bluuebunny/crossref_metadata_2025 huggingface dataset:
Taiwan schizophrenia linkage study: Lessons learned from endophenotype‐based genome‐wide linkage scans and perspective
Authors: Chen Wei J.
Published: October 2013

Taiwan Schizophrenia Linkage Study (TSLS) was initiated with a linkage strategy for locating multiple genes, each of small to moderate effect, and aimed to recruit a large enough sample of pairs of affected siblings and their families ascertained from a multisite study. With a sample of 607 families successfully recruited, a total of 2,242 individuals (1,207 affected and 1,035 unaffected) from 557 families were genotyped using 386 microsatellite markers spaced at an average of 9‐cM intervals. Here the author reviews the establishment of TSLS and initial signal derived from linkage scan using the diagnosis of schizophrenia. Based on the limited success of the initial linkage analysis, a sufficient‐component causal model is proposed to incorporate endophenotypes and genes for schizophrenia. Four types of candidate endophenotype measured in TSLS, including schizotypal personality, Continuous Performance Test, Wisconsin Card Sorting Test, and niacin skin flush test, are briefly described. The author discusses different strategies of linkage analysis incorporating these endophenotypes, including quantitative trait loci (QTL) linkage analysis, clustering‐derived subgroups, ordered subset analysis (OSA), and latent classes for linkage scan. Then the author summarizes the linkage signals generated from seven studies of endophenotype‐based linkage analysis using TSLS, including QTL scan of neurocognitive performance, QTL scan of niacin skin flush, the family cluster of attention deficit and execution deficit, OSA by schizophrenia–schizotypy factors, nested OSA by age at onset and neurocognitive performance, and the latent class of deficit schizophrenia for linkage analysis. The perspective of combining next‐generation sequencing with linkage analysis of families is also discussed. © 2013 Wiley Periodicals, Inc.
A review of neuroimaging studies of young relatives of individuals with schizophrenia: A developmental perspective from schizotaxia to schizophrenia
Authors: Thermenos H.W. , Keshavan M.S. , Juelich R.J. , Molokotos E. , Whitfield‐Gabrieli S. , Brent B.K. , Makris N. , Seidman L.J.
Published: October 2013

In an effort to identify the developing abnormalities preceding psychosis, Dr. Ming T. Tsuang and colleagues at Harvard expanded Meehl's concept of “schizotaxia,” and examined brain structure and function in families affected by schizophrenia (SZ). Here, we systematically review genetic (familial) high‐risk (HR) studies of SZ using magnetic resonance imaging (MRI), examine how findings inform models of SZ etiology, and suggest directions for future research. Neuroimaging studies of youth at HR for SZ through the age of 30 were identified through a MEDLINE (PubMed) search. There is substantial evidence of gray matter volume abnormalities in youth at HR compared to controls, with an accelerated volume reduction over time in association with symptoms and cognitive deficits. In structural neuroimaging studies, prefrontal cortex (PFC) alterations were the most consistently reported finding in HR. There was also consistent evidence of smaller hippocampal volume. In functional studies, hyperactivity of the right PFC during performance of diverse tasks with common executive demands was consistently reported. The only longitudinal fMRI study to date revealed increasing left middle temporal activity in association with the emergence of psychotic symptoms. There was preliminary evidence of cerebellar and default mode network alterations in association with symptoms. Brain abnormalities in structure, function and neurochemistry are observed in the premorbid period in youth at HR for SZ. Future research should focus on the genetic and environmental contributions to these alterations, determine how early they emerge, and determine whether they can be partially or fully remediated by innovative treatments. © 2013 Wiley Periodicals, Inc.
Comparing Apparent Magnetic Susceptibility Measurements of a Multi‐receiver EMI Sensor with Topsoil and Profile Magnetic Susceptibility Data over Weak Magnetic Anomalies
Authors: De Smedt Philippe , Saey Timothy , Meerschman Eef , De Reu Jeroen , De Clercq Wim , Van Meirvenne Marc
Published: October 2013

Today, most surveys in archaeogeophysical prospection use magnetic properties to detect archaeological features. Such magnetic surveys are usually conducted with magnetometers and, to a lesser extent, with magnetic susceptibility meters and electromagnetic induction (EMI) sensors. Although the latter are the only instruments that allow mapping multiple physical soil properties simultaneously, EMI remains the odd‐one‐out in archaeogeophysical prospection. Nevertheless, by simultaneously recording the electric and magnetic soil variability, EMI survey can be beneficial in early archaeological evaluation stages, because detailed pedological and archaeological information is gathered at the same time. Furthermore, by using multi‐receiver EMI instruments vertical soil variation also can be integrated into the survey. However, although the potential of EMI for mapping electric soil variations is well known from advances in soil science, magnetic susceptibility measurements have been investigated less. Here we show the potential of a multi‐receiver EMI survey to detect weak magnetic anomalies by measuring the apparent magnetic susceptibility (κa) of multiple soil volumes at a test site. The shallowκadata were compared with topsoil susceptibility measurements using a magnetic susceptibility loop sensor survey, and with magnetic susceptibility profiling using a probe sensor for evaluating the deeperκa‐data. Further comparisons were made between these datasets and aerial photography and field walking data. We found that the multiple EMIκameasurements allowed for a straightforward discrimination of the natural and anthropogenic magnetic variations of shallow and deeper soil volumes, and allowed visualizing weak magnetic anomalies. Copyright © 2013 John Wiley & Sons, Ltd.
Solution‐Processable n‐Type Semiconductors Based on Unsymmetrical Naphthalene Imides: Synthesis, Characterization, and Applications in Field‐Effect Transistors
Authors: Shao Jinjun , Chang Jingjing , Chi Chunyan
Published: October 2013

A series of unsymmetrical naphthalene imide derivatives (1a, 1b, 2, 3, 4, 5) with high electron affinity was synthesized and used in n‐channel organic field‐effect transistors (OFETs). They have very good solubility in common organic solvents and good thermal stability up to 320 °C. Their photophysical, electrochemical, and thermal properties were investigated in detail. They showed low‐lying LUMO energy levels from −3.90 to −4.15 eV owing to a strong electron‐withdrawing character. Solution‐processed thin‐film OFETs based on 1a, 1b, 2, 3, 4 were measured in both N2 and air. They all showed n‐type FET behavior. The liquid‐crystalline compounds 1a, 1b, and 3 showed good performance owing to the self‐healing properties of the film in the liquid‐crystal phase. Compound 3 has an electron mobility of up to 0.016 cm2 V−1 s−1 and current on/off ratios of 104–105.
The McGurk Effect in Children With Autism and Asperger Syndrome
Authors: Bebko James M. , Schroeder Jessica H. , Weiss Jonathan A.
Published: October 2013

Children with autism may have difficulties in audiovisual speech perception, which has been linked to speech perception and language development. However, little has been done to examine children with Asperger syndrome as a group on tasks assessing audiovisual speech perception, despite this group's often greater language skills. Samples of children with autism, Asperger syndrome, and Down syndrome, as well as a typically developing sample, were presented with an auditory‐only condition, a speech‐reading condition, and an audiovisual condition designed to elicit the McGurk effect. Children with autism demonstrated unimodal performance at the same level as the other groups, yet showed a lower rate of the McGurk effect compared with the Asperger, Down and typical samples. These results suggest that children with autism may have unique intermodal speech perception difficulties linked to their representations of speech sounds. Autism Res 2014, 7: 50–59. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Systems pharmacology modeling: an approach to improving drug safety
Authors: Bai Jane P. F. , Fontana Robert J. , Price Nathan D. , Sangar Vineet
Published: October 2013

Advances in systems biology in conjunction with the expansion in knowledge of drug effects and diseases present an unprecedented opportunity to extend traditional pharmacokinetic and pharmacodynamic modeling/analysis to conduct systems pharmacology modeling. Many drugs that cause liver injury and myopathies have been studied extensively. Mitochondrion‐centric systems pharmacology modeling is important since drug toxicity across a large number of pharmacological classes converges to mitochondrial injury and death. Approaches to systems pharmacology modeling of drug effects need to consider drug exposure, organelle and cellular phenotypes across all key cell types of human organs, organ‐specific clinical biomarkers/phenotypes, gene–drug interaction and immune responses. Systems modeling approaches, that leverage the knowledge base constructed from curating a selected list of drugs across a wide range of pharmacological classes, will provide a critically needed blueprint for making informed decisions to reduce the rate of attrition for drugs in development and increase the number of drugs with an acceptable benefit/risk ratio. Copyright © 2013 John Wiley & Sons, Ltd.
The contribution of ‘shared education’ to Catholic–Protestant reconciliation in Northern Ireland: a third way?
Authors: Borooah Vani K. , Knox Colin
Published: October 2013

Northern Ireland has achieved political stability and its devolved government is now tackling public policy issues neglected during periods of sectarian violence. Notwithstanding the prevailing political optimism, one legacy of the conflict is a deeply divided society. This is particularly manifest in the education system where around 90% of children attend either state (controlled) schools (de facto Protestant) or Catholic (maintained) schools, with integrated schools accounting for less than 6% of the school population. In an attempt to address this duplication of services, in the context of 85,000 empty desks, external funders have piloted an initiative entitled The Shared Education Programme (SEP) where schools working in cross‐community partnerships deliver shared classes and activities in order to improve education outcomes. This paper attempts to: quantify the educational returns for pupils participating in the SEP; articulate the qualitative reconciliation benefits from the perspective of teachers, parents and pupils; and, locate the findings of the research in the ongoing policy debate about restructuring education provision in Northern Ireland at a time of budget retrenchment and declining school rolls.
Modified Jiu Wei Qiang Huo decoction improves dysfunctional metabolomics in influenza A pneumonia‐infected mice
Authors: Chen Lijuan , Fan Jiajun , Li Yubin , Shi Xunlong , Ju Dianwen , Yan Qianlin , Yan Xin , Han Lei , Zhu Haiyan
Published: October 2013

In order to study the effective mechanism of a traditional Chinese medicine (TCM), modified Jiu Wei Qiang Huo decoction (MJWQH), against H1N1‐induced pneumonia in mice, we chose a holistic approach. A reverse‐phase liquid chromatography with quadruple time‐of‐flight mass spectrometry (LC‐Q‐TOF‐MS) was developed to determine metabolomic biomarkers in mouse serum for the MJWQH effects. Thirteen biomarkers of H1N1‐induced pneumonia in mice serum were identified, which comprised l‐valine, lauroylcarnitine, palmitoyl‐l‐carnitine, l‐ornithine, uric acid, taurine, O‐succinyl‐l‐homoserine, l‐leucine, l‐phenylalanine, PGF2α, 20‐ethyl‐PGE2, arachidonic acid, and glycerophospho‐N‐arachidonoyl ethanolamine. Among them, metabolites of amino acids, fatty acids and arachidonic acid had the most relevant changes in mice with H1N1‐induced pneumonia. MJWQH effectively improved weight loss, lung index, biomarkers and inflammatory mediators such as prostaglandin E2 and phospholipase A2 in the infected mice. Importantly, MJWQH reversed the elevated biomarkers to the control levels from the infection, which provided a systematic view and a theoretical basis for its prevention or treatment. The results suggest that the protective effect of MJWQH against H1N1‐induced pneumonia is possibly through regulation of pathways for amino acid, fatty acid and arachidonic acid metabolism. They also suggest that the LC‐MS‐based metabolomic strategy is a powerful tool for elucidation of the mechanisms of TCM. Copyright © 2013 John Wiley & Sons, Ltd.
Defect‐enhanced Photocatalytic Activity of ZnO Micro/nanostructures
Authors: Wang Yu , Yan Mei , Chen Qinguo , Peng Yin
Published: October 2013

ZnO micro/nanocrystals with controlled oxygen defects are successfully prepared through annealing precursors obtained via a simple solvothermal method. The size and surface defects of the as‐synthesized ZnO micro/nanocrystals increase with the solvent volume ratio of water/ethanol increasing; the BET surface areas of the corresponding samples decrease during these processes; photoluminescence reveals that the type and concentration of surface defects (oxygen vacancy and interstitial oxygen) are quite different for the samples prepared via different solvent volume ratio of water/ethanol. In addition, it is found that the photocatalytic activity of the synthesized ZnO nanocrystals is mainly dependent on the concentration of surface defects. The sample with more surface defects exhibits higher photocatalytic activity toward the degradation of methylene blue (MB). The possible photocatalytic mechanism is discussed in detail.
Cross‐Coupling Reactions of Pyrimidin‐2‐yl Sulfonates with Phenols and Anilines: An Efficient Approach to C2‐Functionalized Pyrimidines
Authors: Quan Zhengjun , Jing Fuqiang , Zhang Zhang , Da Yuxia , Wang Xicun
Published: October 2013

Pyrimidin‐2‐yl sulfonates, as an efficient reaction partner, which can be easily prepared from cheap commercial materials, were coupled with phenols and anilines to give a wide array of C2‐aryloxy‐ and arylaminopyrimidines in good to excellent yields under mild reaction conditions.
Synthesis of 2‐Azido‐4‐nitroimidazole and Its Derivatives for High‐Energy Materials
Authors: Hou Kehui , Ma Congming , Liu Zuliang
Published: October 2013

2‐Azido‐4‐nitroimidazole and its derivatives have been synthesized for energetic material applications. The synthesized compounds were fully characterized by 1H, 13C NMR spectroscopy and elemental analysis. Most of them were determined by single crystal X‐ray diffraction. The calculated densities of the compounds range between 1.71 and 1.92 g·cm−3. The calculated detonation pressures (P) for these derivatives fall in the range of 25.17 to 32.62 GPa and the detonation velocities (D) are distributed from 7.65 to 8.55 km·s−1.
Synthesis of Novel Glycidol Copolymers with Pendant Alkene and Hydroxyl Groups
Authors: Liu Siwei , Zhang Feng , Zhang Yi , Xu Jiarui
Published: October 2013

A series of linear poly glycidol copolymers, tethering with both alkene and hydroxyl groups, were prepared by a combination of anionic ring‐opening polymerization (ROP) using specific reactions of ethoxy ethyl glycidyl ether (EEGE) and allyl glycidyl ether (AGE) firstly, and subsequently removal of the protection group of glycidol in EEGE to achieve the linear copolymer pendant with both hydroxyl groups and double bonds. The EEGE/AGE monomer reactivity ratio is measured to be 3.30/1.13. The chemical compositions of the as‐synthesized polymers were characterized by 1H NMR and GPC, and the glass transition temperatures (Tg) of as‐synthesized polymers were determined by DSC. The final copolymers have abundant double bonds and hydroxyl as side groups. Furthermore, the ratio of the double bonds to hydroxyl groups can be controlled by the ratio of the starting materials in a wide range.
Accumulation of Fluoride by Plants: Potential for Phytoremediation
Authors: Baunthiyal Mamta , Ranghar Shweta
Published: October 2013

Fluoride pollution is now recognized as a global problem. The reason fluorides are considered as serious contaminants even when they are present at low levels is that they persist for a long time in air, soil, and water and exert negative effects at all levels of an ecosystem. Thus, immediate attention is the need of the hour to remediate the environment from F pollution. Till date, the conventional methods have been developed primarily to remove F from water. These methods are very slow and expensive. Besides, not much research has been done so far to remediate F from soil. This review focuses on the uptake and accumulation of F by certain aquatic and land plant species. Exploring these plants by analysis of their tissues for accumulated contaminants may open up several opportunities to be utilized to remediate F rich water and soil.
A real‐time Java tool chain for resource constrained platforms
Authors: Korsholm Stephan E. , Søndergaard Hans , Ravn Anders P.
Published: October 2013

The Java programming language was originally developed for embedded systems, but the resource requirements of previous and current Java implementations – especially memory consumption – tend to exclude them from being used on a significant class of resource constrained embedded platforms. The contribution of this paper is an architecture and implementation of a Java execution stack for resource constrained embedded platforms with a few kB of RAM and flash memory. The resource requirements of the presented architecture has been reduced significantly through all the layers of the architecture by integrating the following: (1) a lean virtual machine without any external dependencies on POSIX‐like libraries or other OS functionalities; (2) a hardware abstraction layer, implemented almost entirely in Java through the use of hardware objects, first level interrupt handlers, and native variables; and (3) an implementation of the Safety‐Critical Java profile Level 0 and 1 for hard real‐time applications. All Java components of a given application are minimized through program specialization, and because (2) and (3) are written in Java, the program specialization has a significant impact on the resulting program size. An evaluation of the presented solution shows that the miniCDj benchmark gets reduced to a size where it can run on resource constrained platforms. Copyright © 2013 John Wiley & Sons, Ltd.
Precursors of Developmental Dyslexia: An Overview of the Longitudinal Dutch Dyslexia Programme Study
Authors: van der Leij Aryan , van Bergen Elsje , van Zuijen Titia , de Jong Peter , Maurits Natasha , Maassen Ben
Published: October 2013

Converging evidence suggests that developmental dyslexia is a neurobiological disorder, characterized by deficits in the auditory, visual, and linguistic domains. In the longitudinal project of the Dutch Dyslexia Programme, 180 children with a familial risk of dyslexia (FR) and a comparison group of 120 children without FR (noFR) were followed from the age of 2 months up to 9 years. Children were assessed on (1) auditory, speech, and visual event‐related potentials every half year between 2 and 41 months; (2) expressive and receptive language, motor development, behaviour problems, and home‐literacy environment by questionnaires at the age of 2 and 3; (3) speech–language and cognitive development from 47 months onwards; and (4) preliteracy and subskills of reading, and reading development during kindergarten and Grades 2 and 3.

With regard to precursors of reading disability, first analyses showed specific differences between FR and noFR children in neurophysiological, cognitive, and early language measures. Once reading tests administered from age 7 to 9 years were available, the children were divided into three groups: FR children with and without dyslexia, and controls. Analyses of the differences between reading groups yielded distinct profiles and developmental trajectories. On early speech and visual processing, and several cognitive measures, performance of the non‐dyslexic FR group differed from the dyslexic FR group and controls, indicating continuity of the influence of familial risk. Parental reading and rapid naming skills appeared to indicate their offspring's degree of familial risk. Furthermore, on rapid naming and nonverbal IQ, the non‐dyslexic FR group performed similarly to the controls, suggesting protective factors. There are indications of differences between the FR and control groups, irrespective of reading outcome. These results contribute to the distinction between the deficits correlated to dyslexia as a manifest reading disorder and deficits correlated to familial risk only. Copyright © 2013 John Wiley & Sons, Ltd.
Gene signatures related to B‐cell proliferation predict influenza vaccine‐induced antibody response
Authors: Tan Yan , Tamayo Pablo , Nakaya Helder , Pulendran Bali , Mesirov Jill P. , Haining W. Nicholas
Published: October 2013

Vaccines are very effective at preventing infectious disease but not all recipients mount a protective immune response to vaccination. Recently, gene expression profiles of PBMC samples in vaccinated individuals have been used to predict the development of protective immunity. However, the magnitude of change in gene expression that separates vaccine responders and nonresponders is likely to be small and distributed across networks of genes, making the selection of predictive and biologically relevant genes difficult. Here we apply a new approach to predicting vaccine response based on coordinated upregulation of sets of biologically informative genes in postvaccination gene expression profiles. We found that enrichment of gene sets related to proliferation and immunoglobulin genes accurately segregated high responders to influenza vaccination from low responders and achieved a prediction accuracy of 88% in an independent clinical trial. Many of the genes in these gene sets would not have been identified using conventional, single‐gene level approaches because of their subtle upregulation in vaccine responders. Our results demonstrate that gene set enrichment method can capture subtle transcriptional changes and may be a generally useful approach for developing and interpreting predictive models of the human immune response.
Site‐Selective Sonogashira Reactions of 1,4‐Dibromo‐2‐(trifluoromethyl)benzene: Synthesis and Properties of Fluorinated Alkynylbenzenes
Authors: Reimann Sebastian , Wittler Kai , Schmode Stella , Sharif Muhammad , Fahrenwaldt Thomas , Ludwig Ralf , Spannenberg Anke , Langer Peter
Published: October 2013

Site‐selective Sonogashira cross‐coupling reactions of 1,4‐dibromo‐2‐(trifluoromethyl)benzene have been performed, affording a variety of functionalized alkynyl‐substituted (trifluoromethyl)benzenes. The site selectivity, in favor of position C‐4, was confirmed by 13C NMR and 1H–13C HMBC NMR measurements, X‐ray crystal structure analysis as well as DFT calculations. Furthermore, the mesomorphic properties and optical textures were examined by differential scanning calorimetry and polarized optical microscopy. Several dialkynyl‐substituted (trifluoromethyl)benzenes showed nematic liquid‐crystalline properties over a long phase range. The influence of terminal and lateral substituents on the formation and stability of the molecular network within the liquid‐crystalline phase is explained by the results of DFT calculations. Additionally, the absorption and fluorescence properties were analyzed in detail. The intramolecular influence of electron‐donating or electron‐withdrawing groups and also of solvatochromatism are considered. In this context, time‐dependent B3LYP/6‐31G* (TD‐B3LYP) calculations were carried out to characterize the main absorption bands.
Contamination of therapeutic human immunoglobulin preparations with apolipoprotein H (β2‐glycoprotein I)
Authors: Lackner Friedrich , Beck Gerhard , Eichmeir Stephanie , Gemeiner Manfred , Hummel Karin , Pullirsch Dieter , Razzazi‐Fazeli Ebrahim , Seifner Alexandra , Miller Ingrid
Published: October 2013

Polyclonal immunoglobulin (Ig) concentrates are important biological medicinal products and the assurance of their quality and safety is crucial. In our present approach we used proteomic methods to check the purity of commercial Ig products of different origin. The experimental setup included nonreducing 2DE or DIGE combined with MALDI‐TOF and the thrombin generation assay, a routine safety test for pharmaceutical Ig preparations, and was complemented by a specific immunoassay. 2DE patterns displayed contaminations with trace amounts of human apolipoprotein H (Apo‐H), transferrin, albumin, and its fragments. In contrast to the latter, Apo‐H is a protein that is active in the coagulation cascade, and thus a potential involvement in thromboembolic events in vivo cannot be excluded. It was found by 2DE and MALDI‐TOF to be a contaminant of several Ig preparations. Spiking experiments of Ig preparations with pure Apo‐H demonstrated an Apo‐H concentration dependent increase in thrombin generation assay values. Traces of Apo‐H are possibly also contributing to unwanted side effects, as already known for factor XIa. The significance of Apo‐H contaminations for these side effects might be verified by detailed analyses of pharmacovigilance data.
Alterations in streaming potential in presence of time periodic pressure‐driven flow of a power law fluid in narrow confinements with nonelectrostatic ion–ion interactions
Authors: Dhar Jayabrata , Ghosh Uddipta , Chakraborty Suman
Published: October 2013

We study the coupled effect of electrokinetic phenomena and fluid rheology in altering the induced streaming potential in narrow fluidic confinements, which is manifested by establishing a time periodic pressure‐driven flow in presence of electrical double layer phenomenon. However, in sharp contrast with reported literature, we take into account nonelectrostatic ion–ion interactions toward estimating the same in addition to electrostatic interactions and steric effects. We employ power law based rheological model for estimating the induced streaming potential. We bring out an intricate interaction between nonelectrostatic interactions and fluid rheology on the concerned electrokinetic phenomena, bearing immense consequences toward designing of integrated lab‐on‐a‐chip‐based microdevices and nanodevices.
THE POVERTY EFFECTS OF A ‘FAT‐TAX’ IN IRELAND
Authors: Madden David
Published: October 2013

To combat growing levels of obesity, health‐related taxes have been suggested with taxes on foods high in fat or sugar. Such taxes have been criticised on the basis of their regressivity and potentially adverse impact upon poverty. This paper analyses the effect of such taxes on a range of poverty measures and also examines the effect of a revenue‐neutral tax subsidy mixed with a tax on unhealthy food combined with a subsidy on more healthy food. Using Irish expenditure data, the results indicate that taxes on high fat/sugar goods on their own will be regressive but that a tax‐subsidy combination can be broadly neutral with respect to poverty. Copyright © 2013 John Wiley & Sons, Ltd.
Overexpression of the polarity protein PAR‐3 in clear cell renal cell carcinoma is associated with poor prognosis
Authors: Dugay F. , Le Goff X. , Rioux‐Leclerq N. , Chesnel F. , Jouan F. , Henry C. , Cabillic F. , Verhoest G. , Vigneau C. , Arlot‐Bonnemains Y. , Belaud‐Rotureau MA.
Published: October 2013

The partition‐defective 3 (PAR‐3) protein is implicated in the development and maintenance of cell polarity and is associated with proteins that mediate the changes in cytoskeleton organization required for cell polarity establishment. In this work, we used two original primary cell lines (R‐180 and R‐305) derived from clear cell Renal Cell Carcinoma (ccRCC) surgical specimens of a patient with unfavorable clinical course (R‐180 cells) and a patient with favorable prognosis (R‐305 cells) to identify genetic and molecular features that may explain the survival difference of the two patients. The cytogenetic analysis of these cell lines revealed that the PARD3 gene was amplified only in the R‐180 cell line that was derived from an aggressive ccRCC. PARD3 gene amplification was associated with overexpression of the encoded protein and altered cytoskeleton organization. Consistently, PARD3 knockdown in R‐180 cells restored the cytoskeleton organization and reduced cell migration in comparison to non‐transfected cells. Immunohistochemical analysis of ccRCC samples from a cohort of 96 patients with a follow‐up of 6 years revealed that PAR‐3 overexpression was correlated with poor survival. Our results suggest that PAR‐3 has a role in the clinical aggressiveness of ccRCC, possibly by promoting cell migration.
Cervical cancer cell‐derived interleukin‐6 impairs CCR7‐dependent migration of MMP‐9‐expressing dendritic cells
Authors: Pahne‐Zeppenfeld Jennifer , Schröer Nadine , Walch‐Rückheim Barbara , Oldak Monika , Gorter Arko , Hegde Subramanya , Smola Sigrun
Published: October 2013

Cervical carcinogenesis is a consequence of persistent infection with high‐risk human papillomaviruses (HPVs). Recent studies indicate that HPV‐transformed cells actively instruct their microenvironment to promote carcinogenesis. Here, we demonstrate that cervical cancer cells activate monocytes to produce their own CCL2 for further monocyte recruitment and reprogram their function during differentiation and maturation to dendritic cells (DCs). Our data show that cervical cancer cells suppress the induction of the chemokine receptor CCR7 in phenotypically mature DCs and impair their migration toward a lymph node homing chemokine, required to initiate adaptive immune responses. We confirmed the presence of CD83+CCR7low DCs in cancer biopsies. The second factor essential for DC migration, matrix‐metalloproteinase MMP‐9, which also has vasculogenic and protumorigenic properties, is not suppressed but upregulated in immature as well as mature DCs. We identified interleukin‐6 (IL‐6) as a crucial cervical cancer cell‐derived mediator and nuclear factor kappaB (NF‐κB) as the central signaling pathway targeted in DCs. Anti‐IL‐6 antibodies reverted not only NF‐κB inhibition and restored CCR7‐dependent migration but also blocked MMP‐9 induction. This is the first report demonstrating the dissociation of CCR7 and MMP‐9 expression in phenotypically mature CD83+ DCs by cancer cells. Our results show that cervical cancer cells actively shape the local microenvironment. They induce the accumulation of myeloid cells and skew their function from immune activation to local production of protumorigenic MMP‐9. Neutralizing anti‐IL‐6 antibodies can counteract this functional dysbalance and should therefore be considered for adjuvant cervical cancer therapy.
Chernobyl fallout and cancer incidence in Finland 1988–2007
Authors: Auvinen Anssi , Seppä Karri , Pasanen Kari , Kurttio Päivi , Patama Toni , Pukkala Eero , Heinävaara Sirpa , Arvela Hannu , Verkasalo Pia , Hakulinen Timo
Published: October 2013

Twenty‐five years have passed since the Chernobyl accident, but its health consequences remain to be well established. Finland was one of the most heavily affected countries by the radioactive fallout outside the former Soviet Union. We analyzed the relation of the estimated external radiation exposure from the fallout to cancer incidence in Finland in 1988–2007. The study cohort comprised all ∼3.8 million Finns who had lived in the same dwelling for 12 months following the accident (May 1986–April 1987). Radiation exposure was estimated using data from an extensive mobile dose rate survey. Cancer incidence data were obtained for the cohort divided into four exposure categories (the lowest with the first‐year committed dose <0.1 mSv and the highest ≥0.5 mSv) allowing for a latency of 5 years for leukemia and thyroid cancer, and 10 years for other cancers. Of the eight predefined cancer sites regarded as radiation‐related from earlier studies, only colon cancer among women showed an association with exposure from fallout [excess rate ratio per increment in exposure category 0.06, 95% confidence interval (CI) 0.02–0.11]. No such effect was observed for men, or other cancer sites. Our analysis of a large cohort over two decades did not reveal an increase in cancer incidence following the Chernobyl accident, with the possible exception of colon cancer among women. The largely null findings are consistent with extrapolation from previous studies suggesting that the effect is likely to remain too small to be empirically detectable and of little public health impact.
Mental imagery in chronic pain: Prevalence and characteristics
Authors: Gosden T. , Morris P.G. , Ferreira N.B. , Grady C. , Gillanders D.T.
Published: October 2013

Background

Research into mental imagery has increased our understanding of a range of psychological problems. However, there has been little study into the spontaneous mental images experienced in response to chronic pain. This study aimed to explore the prevalence and characteristics of these pain‐related mental images.

Methods

Four hundred ninety‐one people with chronic pain who had attended a pain clinic were sent invites to participate and 105 people responded (21%). A mixed‐methods approach (quantitative and qualitative) was used to explore the prevalence of pain‐related mental imagery, differences between imagers and non‐imagers, and the content of imagery in pain.

Results

In our sample, 36% of respondents reported having mental images of their pain, with the majority describing them as clear and vivid (83%), experienced daily (80.5%), and distressing (83%). Participants who experienced mental images reported higher depression scores, higher anxiety and higher pain unpleasantness. Frequency of imagery was associated with greater pain unpleasantness. Content analysis of the pain images revealed emerging themes relating to the sensory qualities of pain, anatomical representations, pain as a form of threat or attack, pain as an object, and pain as an abstract image.

Conclusions

This study describes themes and characteristics of pain‐related mental imagery and confirms that they are a frequent, vivid and distressing experience for many chronic pain sufferers. The results of this study suggest that pain‐related mental imagery could provide an additional route for assessment and intervention. Further research should focus on assessment, measurement and intervention in clinical populations.
Melt‐electrospun polycaprolactone strontium‐substituted bioactive glass scaffolds for bone regeneration
Authors: Ren Jiongyu , Blackwood Keith A. , Doustgani Amir , Poh Patrina P. , Steck Roland , Stevens Molly M. , Woodruff Maria A.
Published: October 2013

Polycaprolactone (PCL) is a resorbable polymer used extensively in bone tissue engineering owing to good structural properties and processability. Strontium‐substituted bioactive glass (SrBG) has the ability to promote osteogenesis and may be incorporated into scaffolds intended for bone repair. Here, we describe for the first time, the development of a PCL‐SrBG composite scaffold incorporating 10% (weight) of SrBG particles into PCL bulk, produced by the technique of melt electrospinning. We show that we are able to reproducibly manufacture composite scaffolds with an interconnected porous structure and, furthermore, these scaffolds were demonstrated to be noncytotoxic in vitro. Ions present in the SrBG component were shown to dissolve into cell culture media and promoted precipitation of a calcium phosphate layer on the scaffold surface which in turn led to noticeably enhanced alkaline phosphatase activity in MC3T3‐E1 cells compared to PLC‐only scaffolds. These results suggest that melt‐electrospun PCL‐SrBG composite scaffolds show potential to become effective bone graft substitutes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3140–3153, 2014.
Preparation and degradation study of photocurable oligolactide‐HA composite: A potential resin for stereolithography application
Authors: Tanodekaew Siriporn , Channasanon Somruethai , Uppanan Paweena
Published: October 2013

The merging of stereolithography (SLA) technology to the medical field certainly benefits the manufacturing of parts, especially those patient‐specific for the clinical use. This technique, however, has hardly been exploited medically due to a limited number of biodegradable resins for SLA processing. To extend application of SLA in the biomedical field, photocurable oligolactide resins were developed and examined for biodegradation and biocompatibility. The degradation was studied by monitoring the changes in weight loss, and thermal and mechanical properties of the photocured specimens in phosphate buffered saline (PBS) at 37°C. The results demonstrated that a resin composition played an important role in degradation, and the retarded degradation rate was observed for the highly crosslinked resin containing hydroxyapatite (HA). The less cytotoxic sample was also obtained from the resin with higher content of HA. These findings suggest the possible use of the developed photocurable oligolactide resins in SLA manufacturing of biodegradable implants, where their degradation behaviors can be designed by varying the resin composition. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 604–611, 2014.
Sonographic diagnosis of ascariasis causing small bowel obstruction
Authors: Aydin Ramazan , Bekci Tumay , Bilgici Meltem Ceyhan , Polat Ahmet Veysel
Published: October 2013

Acute right lower quadrant pain is a common, but nonspecific presenting symptom of a wide variety of diseases in children. Sonography (US) can play a significant role in the accurate and early diagnosis of right lower quadrant pain. In this article, we report a case of small bowel obstruction due to intestinal ascariasis diagnosed at bedside US and confirmed by MRI and describe a new US sign of intestinal ascariasis. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:227–229, 2014
Affinity Research Groups in Practice: Apprenticing Students in Research
Authors: Villa Elsa Q. , Kephart Kerrie , Gates Ann Q. , Thiry Heather , Hug Sarah
Published: October 2013

Background

The affinity research group (ARG) model is a set of practices built on a cooperative team framework to support the creation and maintenance of dynamic and inclusive research groups in which students learn and apply the knowledge and skills required for research and cooperative work. Using situated learning theory, we conducted a qualitative study of current and former ARG members to understand the potential of the ARG for preparing students for graduate school and professional research careers.

Purpose

Our study investigated how the ARG model influenced students, particularly those from underrepresented groups, in becoming researchers and practicing computer scientists.

Design/Method

We employed multiple data collection methods, including individual and focus group interviews and participant observation, to investigate whether this model had lasting effects and sustainability beyond the time students spent in an ARG.

Results

Using themes emerging from our data analysis, we can explain how students become contributing members of ARGs, group identity and cohesiveness are formed, members learn collaboratively, members participate in larger professional communities, and participants' identities are transformed from student to researcher.

Conclusions

Findings suggest that the structural and procedural elements of ARGs support students' growth and development as researchers and their gradual socialization into broader computer science research and professional communities through legitimate peripheral participation and immersion in situated practice.
Fidelity of Implementation of Research‐Based Instructional Strategies (RBIS) in Engineering Science Courses
Authors: Borrego Maura , Cutler Stephanie , Prince Michael , Henderson Charles , Froyd Jeffrey E.
Published: October 2013

Background

Increasing attention is being paid to improvement in undergraduate science, technology, engineering, and mathematics (STEM) education through increased adoption of research‐based instructional strategies (RBIS), but high‐quality measures of faculty instructional practice do not exist to monitor progress.

Purpose/Hypothesis

The measure of how well an implemented intervention follows the original is called fidelity of implementation. This theory was used to address the research questions: What is the fidelity of implementation of selected RBIS in engineering science courses? That is, how closely does engineering science classroom practice reflect the intentions of the original developers? Do the critical components that characterize an RBIS discriminate between engineering science faculty members who claimed use of the RBIS and those who did not?

Design/Method

A survey of 387 U.S. faculty teaching engineering science courses (e.g., statics, circuits, thermodynamics) included questions about class time spent on 16 critical components and use of 11 corresponding RBIS. Fidelity was quantified as the percentage of RBIS users who also spent time on corresponding critical components. Discrimination between users and nonusers was tested using chi square.

Results

Overall fidelity of the 11 RBIS ranged from 11% to 80% of users spending time on all required components. Fidelity was highest for RBIS with one required component: case‐based teaching, just‐in‐time teaching, and inquiry learning. Thirteen of 16 critical components discriminated between users and nonusers for all RBIS to which they were mapped.

Conclusions

Results were consistent with initial mapping of critical components to RBIS. Fidelity of implementation is a potentially useful framework for future work in STEM undergraduate education.
Light sheet based imaging flow cytometry on a microfluidic platform
Authors: regmi Raju , Mohan Kavya , Mondal Partha P.
Published: October 2013

We propose a light sheet based imaging flow cytometry technique for simultaneous counting and imaging of cells on a microfluidic platform. Light sheet covers the entire microfluidic channel and thus omits the necessity of flow focusing and point scanning based technology. Another advantage lies in the orthogonal detection geometry that totally cuts‐off the incident light, thereby substantially reducing the background in the detection. Compared to the existing state‐of‐art techniques the proposed technique shows marked improvement. Using fluorescently‐coated Saccharomyces cerevisiae cells we have recorded cell counting with throughput as high as 2,090 cells/min in the low flow rate regime and were able to image the individual cells on‐the‐go. Overall, the proposed system is cost‐effective and simple in channel geometry with the advantage of efficient counting in operational regime of low laminar flow. This technique may advance the emerging field of microfluidic based cytometry for applications in nanomedicine and point of care diagnostics. Microsc. Res. Tech. 76:1101–1107, 2013. © 2013 Wiley Periodicals, Inc.
Patients infected with HIV are at high‐risk for hepatitis E virus infection in Spain
Authors: Mateos‐Lindemann Maria Luisa , Diez‐Aguilar María , Galdamez Ana L. Gonzalez , Galán Juan Carlos , Moreno Ana , Pérez‐Gracia María Teresa
Published: October 2013

Hepatitis E virus is responsible for sporadic cases of acute, self‐limited viral hepatitis not only in endemic but also in industrialized countries. In addition, some reports confirm that it can cause chronic infection and even cirrhosis in immunosuppressed and also in patients infected with HIV. There are few data about prevalence and incidence of HEV chronic infection in HIV‐HEV coinfected individuals in Spain. The aim of this study is to investigate the prevalence of anti‐HEV IgG in a representative sample of 448 patients infected with HIV and determine the role of age, gender, and CD4 counts in the detection of anti‐HEV IgG antibodies in blood. In addition, the clinical features and ALT levels in relation to the presence of anti‐HEV IgM and/or HEV‐RNA in the blood of these patients were investigated. Anti‐HEV IgG antibodies were detected in serum using a commercial enzyme immunoassay. All positive samples were studied further for the presence of anti‐HEV IgM antibodies. In addition, HEV RNA was amplified by reverse transcriptase (RT)‐nested PCR in all serum samples with IgM anti‐HEV. The overall prevalence of anti‐HEV IgG was 10.4% (45/448, 95% C.I. 7.2–12.8%). HEV‐RNA was found in only one patient out of the 45 anti‐HEV IgG positive samples studied. Regarding to gender and CD4 count, no difference in seroprevalence could be observed. This prevalence data suggest that patients infected with HIV can be considered a risk group for HEV infection and that chronic coinfection HEV‐HIV seems to be a very rare event. J. Med. Virol. 86:71–74, 2014. © 2013 Wiley Periodicals, Inc.
Integral and analytical models for evaluating the distance of compliance
Authors: Bavastro Davide , Canova Aldo , Giaccone Luca , Manca Michele
Published: October 2013

This paper deals with the magnetic field generated by medium‐voltage/low‐voltage substations. Particularly, the paper focuses on the computation of the distance of compliance that is defined as the minimum distance from a field source for having field levels lower than a given threshold. In the first part of the paper, some 3D integral models are proposed to compute the magnetic field generated by each field source present in substations (transformers, cables, etc...). In the second part of the paper, we make use of these integral models to develop a simplified analytical approach for the computation of an approximate distance of compliance, that is, a conservative distance that includes the previously mentioned distance of compliance. The advantage of this approach is that it is composed of simple equations that are very easy to be implemented without losing the tridimensionality of the problem. Copyright © 2013 John Wiley & Sons, Ltd.
Combined application of low‐intensity pulsed ultrasound and functional electrical stimulation accelerates bone–tendon junction healing in a rabbit model
Authors: Hu Jianzhong , Qu Jin , Xu Daqi , Zhang Tao , Qin Ling , Lu Hongbin
Published: October 2013

The objective of this study was to elucidate the combined use of low‐intensity pulsed ultrasound (LIPUS) and functional electrical stimulation (FES) on patella–patellar tendon (PPT) junction healing using a partial patellectomy model in rabbits. LIPUS was delivered continuously starting day 3 postoperative until week 6. FES was applied on quadriceps muscles to induce tensile force to the repaired PPT junction 5 days per week for 6 weeks since week 7 postoperatively. Forty rabbits with partial patellectomy were randomly divided into four groups: control, LIPUS alone, FES alone, and LIPUS + FES groups. At week 12, the PPT complexes were harvested for histology, radiographs, peripheral quantitative computed tomography, and biomechanical testing. There was better remodeling of newly formed bone and fibrocartilage zone in the three treatment groups compared with the control group. LIPUS and/or FES treatments significantly increased the area and bone mineral content of new bone. The failure load and ultimate strength of PPT complex were also highly improved in the three treatment groups. More new bone formed and higher tensile properties were showed in the LIPUS + FES group compared with the LIPUS or FES alone groups. Early LIPUS treatment and later FES treatment showed the additive effects of accelerating PPT junction healing. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:204–209, 2014.