bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging Game-Play in a 3D World
Authors: Norton-Barker Catherine , Corbit Margaret , Bernstein Richard , Greene Ebonie
Published: February 2011

Computer games have the potential to engage students who do not respond well to traditional classroom activities. To test the appeal and usability of game-play in the classroom, four ninth grade science classes in a rural Upstate New York school were randomly assigned to learn an introductory genetics unit for three class periods in either an online, multi-user, virtual world computer environment or in a traditional classroom setting using lecture, worksheets and model building. The groups were then reversed for a second three-day trial. Quizzes were given before, at midpoint and at the end of the study. Both groups demonstrated significant knowledge gain of the genetics curriculum. This study demonstrates that self-directed learning can occur while exploring virtual world computer environments. The students were enthusiastic about using virtual worlds for education and indicated a strong preference for a variety of teaching methods, which suggests that offering mixed modalities may engage students who are otherwise uninterested in school.
Beyond Choices
Authors: Sicart Miguel
Published: February 2011

This article presents a typology for classifying computer games designed to create ethical gameplay. Ethical gameplay is the outcome of playing a (computer) game in which the players’ moral values are of relevance for the game experience. The article explores the different types of designs that create these types of experiences, and how they are characterized. The author provides an analytical framework for classifying games according to the experience they create and how they create it. The article is informed by both game design theory and postphenomenological philosophy, and it is intended to provide a theoretical framework for the study of the design of ethical computer game experiences.
Antileishmania Immunological Tests for Asymptomatic Subjects Living in a Visceral Leishmaniasis-Endemic Area in Brazil
Authors: Silva Luciana Almeida , Romero Héctor Dardo , Nogueira Nascentes Gabriel Antônio , Costa Roberto Teodoro , Rodrigues Virmondes , Prata Aluízio
Published: February 2011

The objective of this study was to evaluate the behavior of different tests used for the diagnosis of visceral leishmaniasis (VL) in asymptomatic subjects living in an endemic area. No gold standard is available for the diagnosis of asymptomatic infection with Leishmania. In continuation of a previous study, 1,017 subjects living in a VL-endemic area were clinically reevaluated. Of these, 576 had at least one positive serological test in a first assessment. About 3 years after the first evaluation, none of the subjects had progressed to clinical VL. Among this group, 246 subjects were selected, and five serological tests (enzyme-linked immunosorbent assay p [ELISAp], ELISArK39, ELISArK26, indirect immunofluorescence test [IIFT] using L. amazonensis promastigote antigen, and an immunochromatographic test using rK39 antigen [TRALd]) and the Montenegro skin test (MST) were repeated. There was a significant increase in the number of subjects who tested positive in the MST, IIFT, ELISAp, and ELISArK39 in the second evaluation. For all tests, there were subjects who tested positive in the first evaluation and negative in the second evaluation. A positive result in the serological tests and MST in subjects from the endemic area studied did not indicate a risk of progression to VL and may only be temporary.
Drug Resistance Surveillance in Resource-Poor Settings: Current Methods and Considerations for TB, HIV, and Malaria
Authors: Hedt Bethany L. , Laufer Miriam K. , Cohen Ted
Published: February 2011

In resource-constrained environments, monitoring the occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), or malaria resistant to the limited number of available drugs is essential for national treatment program success. Countries with limited resources and technical capacity rely on survey designs and methods that are simple and easily integrated into routine clinical activities to minimize the impact on overburdened clinics. This paper reviews the most commonly used methods for drug-resistance surveillance of TB, HIV, and malaria and discusses the strengths and limitations of these different strategies.
Genetic Polymorphism of Plasmodium vivax msp1p, a Paralog of Merozoite Surface Protein 1, from Worldwide Isolates
Authors: Wang Yue , Kaneko Osamu , Sattabongkot Jetsumon , Chen Jun-Hu , Lu Feng , Chai Jong-Yil , Takeo Satoru , Tsuboi Takafumi , Ayala Francisco J. , Chen Yong , Lim Chae Seung , Han Eun-Taek
Published: February 2011

Plasmodium vivax msp1p, a paralog of the candidate vaccine antigen P. vivax merozoite surface protein 1, possesses a signal peptide at its N-terminus and two epidermal growth factor–like domains at its C-terminus with a glycosylphosphatidylinositol attachment site. The msp1p gene locus may have originated by a duplication of the msp1 gene locus in a common ancestor of the analyzed Plasmodium species and lost from P. yoelii, P. berghei, and P. falciparum during their evolutionary history. Full-length sequences of the msp1p gene were generally highly conserved; they had a few amino acid substitutions, one highly polymorphic E/Q-rich region, and a single-to-triple hepta-peptide repeat motif. Twenty-one distinguishable allelic types (A1–A21) of the E/Q-rich region were identified from worldwide isolates. Among them, four types were detected in isolates from South Korea. The length polymorphism of the E/Q-rich region might be useful as a genetic marker for population structure studies in malaria-endemic areas.
High Throughput Multiplex PCR and Probe-based Detection with Luminex Beads for Seven Intestinal Parasites
Authors: Taniuchi Mami , Verweij Jaco J. , Noor Zannatun , Sobuz Shihab U. , Lieshout Lisette van , Petri William A. , Haque Rashidul , Houpt Eric R.
Published: February 2011

Polymerase chain reaction (PCR) assays for intestinal parasites are increasingly being used on fecal DNA samples for enhanced specificity and sensitivity of detection. Comparison of these tests against microscopy and copro-antigen detection has been favorable, and substitution of PCR-based assays for the ova and parasite stool examination is a foreseeable goal for the near future. One challenge is the diverse list of protozoan and helminth parasites. Several existing real-time PCR assays for the major intestinal parasites—Cryptosporidium spp., Giardia intestinalis, Entamoeba histolytica, Ancylostoma duodenale, Ascaris lumbricoides, Necator americanus, and Strongyloides stercoralis—were adapted into a high throughput protocol. The assay involves two multiplex PCR reactions, one with specific primers for the protozoa and one with specific primers for the helminths, after which PCR products are hybridized to beads linked to internal oligonucleotide probes and detected on a Luminex platform. When compared with the parent multiplex real-time PCR assays, this multiplex PCR-bead assay afforded between 83% and 100% sensitivity and specificity on a total of 319 clinical specimens. In conclusion, this multiplex PCR-bead protocol provides a sensitive diagnostic screen for a large panel of intestinal parasites.
Estimation of the Human Blood Index in Malaria Mosquito Vectors in Equatorial Guinea after Indoor Antivector Interventions
Authors: Pappa Vasiliki , Reddy Michael , Overgaard Hans J. , Abaga Simon , Caccone Adalgisa
Published: February 2011

We determined the Human Blood Index (HBI) of malaria mosquito vectors in Equatorial Guinea. We used a polymerase chain reaction (PCR)-based methodology to identify blood meal sources in engorged mosquitoes. We observed high HBI values, indicating that these vectors are highly anthropophilic despite intensive intradomicillary application of residual insecticides. Our results suggest that estimating the HBI can be a relatively simple and easy way to evaluate the efficacy of antimalaria interventions where an observed diversion to non-human hosts may successfully contribute to the interruption of malaria transmission.
Shell Vial Cell Culture as a Tool for Streptobacillus moniliformis “Resuscitation”
Authors: Loridant Severine , Jaffar-Bandjee Marie-Christine , Scola Bernard La
Published: February 2011

Streptobacillus moniliformis is a fastidious growing Gram-negative bacillus responsible of rat-bite fever. We describe here the first report of this disease in la Réunion and the first isolation using shell vial cell culture from a blood culture bottle with a bacterium suspected to be dead.
Modelling of marine base cation emissions, concentrations and deposition in the UK
Authors: Werner M. , Kryza M. , Dore A. J. , Blaś M. , Hallsworth S. , Vieno M. , Tang Y. S. , Smith R. I.
Published: February 2011

Abstract. Base cations exert a large impact on various geochemical and geophysical processes both in the atmosphere and at the Earth surface. One of the essential roles of these compounds is impact on surface pH causing an increase in alkalinity and neutralizing the effects of acidity generated by sulphur and nitrogen deposition. During recent years anthropogenic emissions of base cations in the UK have decreased substantially, by about 70%, 78%, 75% and 48% for Na+, Mg2+, Ca2+ and K+, respectively, over the period 1990–2006. For the island regions, such as the UK, the main source of base cation particles is the aerosol produced from the sea surface. Here, the sea salt aerosol (SSA) emissions are calculated with parameterisations proposed by Mårtensson et al. (2003) for ultra fine particles, Monahan et al. (1986) for fine particles and Smith and Harisson (1998) for coarse particles continuously with a 0.1 μm size step using WRF-modelled wind speed data at a 5 km × 5 km grid square resolution with a 3 h time step for two selected years 2003 and 2006. SSA production has been converted into base cation emissions, with the assumption that the chemical composition of the particle emitted from the sea surface is equal to the chemical composition of sea water, and used as input data in the Fine Resolution Atmospheric Multi-pollutant Exchange Model (FRAME). FRAME model annual mean concentrations and total wet deposition at a 5 km × 5 km grid resolution, are compared with concentrations in air and wet deposition from the National Monitoring Network and measurements based estimates of UK deposition budget. The correlation coefficient for wet deposition achieves high values (R = 0.8) for Na+ and Mg2+, whereas for Ca2+ the correlation is poor (R < 0.3). Base cation concentrations are also represented well, with some overestimations on the west coast and underestimations in the centre of the land.
Zonal asymmetries in middle atmospheric ozone and water vapour derived from Odin satellite data 2001–2010
Authors: Gabriel A. , Körnich H. , Lossow S. , Peters D. H. W. , Urban J. , Murtagh D.
Published: February 2011

Abstract. Based on Odin satellite data 2001–2010 we investigate stationary wave patterns in middle atmospheric ozone (O3) and water vapour (H2O) as indicated by their seasonal long-term means of the zonally asymmetric components O3* = O3-[O3] and H2O* = H2O-[H2O] ([O3], [H2O]: zonal means). At mid- and polar latitudes of Northern and Southern Hemisphere, we find a pronounced wave one pattern in both constituents. In the Northern Hemisphere, the wave one patterns increase during autumn, maintain their strength during winter and decay during spring, with maximum amplitudes of about 10–20% of zonal mean values. During winter, the wave one in stratospheric O3* is characterized by a maximum over North Pacific/Aleutians and a minimum over North Atlantic/Northern Europe and by a double-peak structure with enhanced amplitude in the lower and in the upper stratosphere. The wave one in H2O* extends from lower stratosphere to upper mesosphere with a westward shift in phase with increasing height including a jump in phase at upper stratosphere altitudes. In the Southern Hemisphere, similar wave one patterns occur during southern spring when the polar vortex breaks down. Based on a simplified tracer transport approach we explain these wave patterns as a first-order result of zonal asymmetries in mean meridional transport by geostrophically balanced winds, which were derived from combined temperature profiles of Odin, and ECMWF (European Centre of Medium-Range Weather Forecasts) Reanalysis data (ERA Interim). Further influences which may contribute to the stationary wave patterns, e.g. eddy mixing processes or temperature-dependent chemistry, are discussed.
Record mass loss from Greenland's best-observed local glacier
Authors: Mernild S. H. , Knudsen N. T. , Lipscomb W. H. , Yde J. C. , Malmros J. K. , Jakobsen B. H. , Hasholt B.
Published: February 2011

Abstract. Warming in the Arctic during the past several decades has caused glaciers to thin and retreat, resulting in increased freshwater runoff to the ocean. Local glaciers peripheral to the ice sheet are also retreating, but few mass-balance observations are available to quantify that retreat and determine the extent to which these glaciers are out of equilibrium with present-day climate. Here, we document record mass loss in 2009/2010 for the Mittivakkat Glacier (henceforth MG), the only local glacier in Greenland for which there exist long-term observations of both the surface mass balance and glacier front fluctuations. We attribute this mass loss to record high mean summer (June–August) and higher-than-average winter (September–May) temperatures and to lower-than-average winter precipitation. Also, we use the 15-year mass-balance record to estimate present-day and equilibrium accumulation-area ratios for the MG. We show that the glacier is significantly out of balance and will likely lose approximately 70% of its current area and 80% of its volume even in the absence of further climate changes. Temperature records from coastal stations in Southeast Greenland suggest that recent MG mass losses are not merely a local phenomenon, but are indicative of glacier changes in the broader region. Mass-balance observations for the MG therefore provide unique documentation of the general retreat of Southeast Greenland's local glaciers under ongoing climate warming.
Efficacy of 3 Different Artificial Tears for the Treatment of Dry Eye in Frequent Computer Users and/or Contact Lens Users
Authors: Calvão-Santos Gil , Borges Cristina , Nunes Sandrina , Salgado-Borges José , Duarte Lilianne
Published: February 2011

Purpose

To compare the efficacy of 3 different artificial tears (AT) acting primarily in one of the 3 tear film layers (Tears Again®, lipidic; Opticol®, aqueous; Optive®, mucin) in recovering the tear film changes in patients with dry eye symptoms due to external causes.

Methods

A total of 27 patients, with dry eye symptoms associated with extra hours of computer or contact lenses use, were randomized to 4 treatment groups: A received Tears Again®; B received Optive®; C received Opticol®; D received no treatment (control). Patients were observed in 3 visits: day 0, day 7, and day 30. Tear break-up time (TBUT) and Schirmer tests and the Ocular Surface Disease Index were performed. Data analysis was performed.

Results

There were no significant differences between the groups. From day 0 to day 30, there was a decrease in the number of eyes with abnormal TBUT (not significant) and Schirmer (significant in A, B, D; p<0.031). There was an increase in the average TBUT for all groups (significant in A, C; p<0.001) and a decrease in the average Schirmer value in groups B, C, and D (not significant) and an increase in group A (p=0.002). There was a decrease in the average Ocular Surface Disease Index value in all groups (p<0.045).

Conclusions

All AT were efficient at recovering the tear film, but those acting primarily on the internal and intermediate layer led to a mild decline on lachrymal production. An association of different kinds of AT acting on each layer can be the best treatment for corneal surface diseases affecting eye lubrication.
Correlation of Mortality and Location of Arteriovenous Fistula in Hemodialysis Patients
Authors: Stolic Radojica V. , Trajkovic Goran Z. , Krstic Nebojsa J. , Stolic Dragica Z. , Subaric-Gorgieva Gordana
Published: February 2011

Purpose

Since the type of vascular access is very important and a significant risk factor for mortality in patients on hemodialysis, the aim of our study was to determine the impact of AVF positioning on the mortality of our patients.

Methods

The survey was organized as a prospective, clinical and non-randomized study of 538 surgical interventions on 323 patients, which indicates that a large number of patients had more than one fistula. Among these patients, 120 subjects (81 (67.5%) men and 39 (32.5%) women) died during the study period. We analyzed the demographic structure, the site location and type of anastomosis for the arteriovenous fistula, artery and vein lumen and presence of instillation catheters, as well as measuring flow through the fistula and arterial blood pressure. Biochemical parameters thought to have a significant impact on survival were obtained from routine monthly analyses.

Results

In patients in whom infection was the cause of death, termino-terminal anastomosis was more frequently present (p=0.035). Variables that were statistically significant predictors of death were elderly individuals (Beta 0.033, p<0.001); patients whose diastolic blood pressure was low (Beta –0.028, p<0.001); and the position of the arteriovenous fistula (distal Beta –0.737, p=0.001; proximal Beta –0.581, p=0.008). Patients with a cubital fistula (p=0.001) had a significantly shorter Kaplan-Meier survival curve.

Conclusions

End-to-end artery and vein connection was a significantly more common form of anastomosis in patients who died as a result of infection. Important parameters of mortality in our study were the position of the arteriovenous fistula, age, and the diastolic component of arterial blood pressure.
The Outcomes of Critically Ill Patients with Acute Kidney Injury Receiving Renal Replacement Therapy
Authors: Lines Simon W. , Cherukuri Aravind , Murdoch Stuart D. , Bellamy Mark C. , Lewington Andrew J.P.
Published: February 2011

Introduction

Acute kidney injury (AKI) is common among critically ill patients and associated with a high mortality. We report here on the outcomes of patients with AKI who received renal replacement therapy (RRT) on our intensive care unit (ICU). We were interested in which parameters measured at the time of ICU admission were predictive of mortality and the long term renal sequelae for these patients.

Patients and Methods

All ICU patients in a large UK teaching hospital who received RRT for AKI over a 6-year period were identified and reviewed retrospectively.

Results

There were 5582 admissions to ICU during this period of which 821 (14.7%) received RRT for AKI. The mean age was 59 years with ICU and hospital mortality rates of 55% and 66% respectively. Logistic regression analysis indicated that being older (OR 1.02 (1.01–1.03)) or having a lower pH (OR 0.07 (0.02–0.27)) or hemoglobin (OR 0.82 (0.74–0.91)) at the time of admission were predictive of mortality. Less than 7% of survivors were RRT dependant at hospital discharge and the majority had pre-existing renal impairment. For those patients with data available, there was a significant rise in the serum creatinine by 12 months post discharge (p<0.001).

Conclusions

The mortality for critically ill patients receiving RRT for AKI is high, with two-thirds dying before hospital discharge. The requirement for long-term dialysis was 6.5% of survivors in our series which is much lower than that published elsewhere. Survivors of AKI who regained independent renal function had evidence of lasting renal injury.
Fibronectin Distribution on Demixed Nanoscale Topographies
Authors: Pérez-Garnes Manuel , González-García Cristina , Moratal David , Rico Patricia , Salmerón-Sánchez Manuel
Published: February 2011

Purpose

It is known that surface nanotopography influences cell adhesion and differentiation. Our aim is to analyze the effect of nanoscale topography on fibronectin adsorption and, afterwards, on cell adhesion in order to rationalize the cell-material interaction by focusing on the state of the intermediate layer of adsorbed fibronectin at the material interphase.

Methods

Nanotopographic surfaces were produced by demixing of thin film polymer blends - PLLA and PS - during a high speed spin-casting process. Fibronectin (FN) was adsorbed on the different nanotopographies and the protein distribution was directly observed by atomic force microscopy (AFM). The fraction of the surface covered by the protein was quantified by image analysis, as well as the distribution of FN between peaks and valleys. Focal adhesion protein –vinculin- was immunostained and quantified by image analysis on the different nanoscale surfaces.

Results

Different nanoscale domains were obtained by changing the composition of the system within a height range of 3 nm to 30 nm. FN tends to adsorb on the peaks of nanoisland topographies, especially in compositions that did not enhance cell adhesion. Moreover, protein distribution between valleys and peaks alters the size of focal adhesion plaques, which grew larger on surfaces with an even distribution of fibronectin.

Conclusions

Our results suggest that the surface nanotopography is a key material property capable of influencing protein adsorption. Additionally, the distribution of the protein on the different samples was correlated to the initial ability of cells to adhere in terms of the size of the focal plaques.
The state of ‘Academic Apartheid’ in Arab Universities: A radical pedagogical analysis
Authors: Abouchedid Kamal
Published: February 2011

This study assesses the reasons that contributed to the rise of ‘Academic Apartheid’ in Arab higher educational institutions, by dwelling on their failure in overcoming alienation from indigenous epistemology, emancipating education from its colonial past, and trudging into the modern information age. Furthermore, the study alludes to the tenuous position of the Arab academic/research in rediscovering the epistemological framework of their indigenous world. The study concludes that the present institutional ‘clanocratic’ approaches to academic administration have ruinous effects on the performance of Arab academia including the arrest of transition toward modernization.
Knowledge management and knowledge sharing for strategic library planning. Value of knowledge sharing for expatriate library professionals
Authors: Kumaresan S.C.
Published: February 2011

This article examines the importance of knowledge management in libraries and the need for motivating and creating a ‘knowledge sharing culture’ within the library. This article also brings out an empirical account of the difficulties library and information science professionals face when they take positions overseas, particularly in a culturally, politically and religiously conservative society and country. Moving to another country means reinventing the wheel once again in a new environment; and if it is to a non-English speaking country it could be a challenging task. One could be in for a ‘culture shock’. In hindsight, it becomes all the more important to know and understand the intricacies of working in such an environment, to build our networks, hone our technical skills and the value of ‘knowledge sharing’. Knowledge management can be very useful in bridging this gap and putting us at ease and get ready for the job. The knowledge management system involves identification of knowledge, capturing, sorting, storing and sharing of pertinent information within the library or various libraries in case of multiple campuses. This article focuses on the issues in knowledge management and the value of knowledge sharing in libraries and tries to advocate the use of knowledge management tools for successful sharing and transfer of knowledge.
Computational fluid dynamics simulations of heat transfer between the dense‐phase of a high‐temperature fluidized bed and an immersed surface
Authors: Soria José M. , Zambon Mariana T. , Mazza Germán D.
Published: February 2011

The transient process of heat transfer between a high‐temperature emulsion packet and the wall of an immersed surface is simulated using computational fluid dynamics (CFD). From these simulations, the total heat transfer coefficient and its radiant contribution due to the emulsion (dense) phase are evaluated. The results are compared with experimental data (Ozkaynak et al., “An experimental investigation of radiant heat transfer in high temperature fluidized beds,” in Fluidization IV, 1983:371–378) and with predicted values from the generalized heterogeneous model (GHM), (Mazza et al., “Evaluation of overall heat transfer rates between bubbling fluidized beds and immersed surfaces,” Chem Eng Commun., 1997;162:125–149). The CFD simulations are in good agreement with both, experimental data and theoretical GHM predictions and provide a reliable way to quantify the studied heat transfer process. Also, the GHM is validated as a practical tool to this end. © 2011 American Institute of Chemical Engineers AIChE J, 58: 412–426, 2012
Syngas production from H2O and CO2 over Zn particles in a packed‐bed reactor
Authors: Stamatiou Anastasia , Loutzenhiser Peter G. , Steinfeld Aldo
Published: February 2011

The solar thermochemical production of H2 and CO (syngas) from H2O and CO2 is examined via a two‐step cycle based on Zn/ZnO redox reactions. The first, endothermic step is the thermolysis of the ZnO driven by concentrated solar energy. The second, nonsolar step is the exothermic reaction of Zn with a mixture of H2O and CO2 yielding syngas and ZnO; the latter is recycled to the first step. A series of experimental runs of the second step was carried out in a packed‐bed reactor where ZnO particles provided an effective inert support for preventing sintering and enabling simple and complete recycling to the first, solar step. Experimentation was performed for Zn mass fractions in the range of 33–67 wt % Zn‐ZnO, and inlet gas concentrations in the range 0–75% H2O–CO2, yielding molar Zn‐to‐ZnO conversions up to 91%. A 25 wt % Zn‐ZnO sample mixture produced from the solar thermolysis of ZnO was tested in the same reactor setup and exhibited high reactivity and conversions up to 96%. © 2011 American Institute of Chemical Engineers AIChE J, 2012
ADHD in Dutch adults: Heritability and linkage study
Authors: Saviouk Viatcheslav , Hottenga Jouke‐Jan , Slagboom Eline P. , Distel Marijn A. , de Geus Eco J.C. , Willemsen Gonneke , Boomsma Dorret I.
Published: February 2011

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental phenotype that persists into adulthood. This study investigated the heritability of inattentive and hyperactive symptoms and of total ADHD symptomatology load (ADHD index) in adults and performed linkage scans for these dimensions. Data on sibling pairs and their family members from the Netherlands Twin Register with genotype and phenotype data for inattention, hyperactivity and ADHD index (∼750 sib‐pairs) were analyzed. Phenotypes were assessed with the short self‐report form of the Conners' Adult ADHD Rating Scales (CAARS). Heritabilities were estimated in SOLAR under polygenic models. Genome‐wide linkage scans were performed using variance components (VC) in MERLIN and MINX and model‐based linkage analysis was carried out in MENDEL with empirical evaluation of the results via simulations. Heritability estimates for inattention, hyperactivity and ADHD index were 35%, 23%, and 31%, respectively. Chromosomes 18q21.31–18q21.32 (VC LOD = 4.58, pemp = 0.0026) and 2p25.1 (LOD = 3.58, pemp = 0.0372) provided significant evidence for linkage for inattention and the ADHD index, respectively. The QTL on chromosome 2p25.1 also showed suggestive linkage for hyperactivity. Two additional suggestive QTLs for hyperactivity and the ADHD index shared the same location on chromosome 3p24.3–3p24.1. Finally, a suggestive QTL on 8p23.3–8p23.2 for hyperactivity was also found. Heritability of inattention, hyperactivity and total ADHD symptoms is lower in adults than in children. Chromosomes 18q and 2p are likely to harbor genes that influence several aspects of adult ADHD. © 2011 Wiley‐Liss, Inc.
Familial transmission of schizophrenia in Palau: A 20‐year genetic epidemiological study in three generations
Authors: Myles‐Worsley Marina , Tiobech Josepha , Blailes Francisca , Middleton Frank A. , Vinogradov Sophia , Byerley William , Faraone Stephen V.
Published: February 2011

Our genetic epidemiological studies of schizophrenia and other psychotic disorders (SCZ) in the isolated population of Palau have been ongoing for 20 years. Results from the first decade showed that Palau has an elevated prevalence of SCZ and that cases cluster in extended multigenerational pedigrees interconnected via complex genetic relationships after centuries of endogamous, but not consanguineous, marriages. The aim of our second decade of research, which extended data collection into a third generation of young, high‐risk (HR) Palauans, was to identify significant predictors of intergenerational transmission of illness. Our findings revealed that degree of familial loading and gender effects on reproductive fitness are important modifiers of risk for transmission of SCZ. Among 45 distinct multiplex families, we identified 10 high‐density (HD) Palauan families, each with 7–29 SCZ cases, which contain half of Palau's 260 SCZ cases and 80% of the 113 SCZ cases with one or more affected first‐degree relatives, indicating that familial loading is a major risk factor for SCZ in Palau. Cases that belong to multiply affected sibships are more common than cases with an affected parent. Furthermore, only 6/38 multiply affected sibships have an affected parent, strong evidence that many unaffected parents are obligate carriers of susceptibility genes. Although reproductive fitness is dramatically reduced in affected males, the 30% minority who do become fathers are twice as likely as affected mothers to transmit SCZ to an offspring. As they evolve, these HD families can help to elucidate the genetic mechanisms that predict intergenerational transmission of SCZ. © 2011 Wiley‐Liss, Inc.
Variation in NGFB is associated with primary affective disorders in women
Authors: Cui Donghong , Zhang Huiping , Yang Bao‐Zhu , Listman Jennifer B. , Li Dawei , Price Lawrence H. , Carpenter Linda L. , Tyrka Audrey R. , Anton Raymond F. , Kranzler Henry R. , Gelernter Joel
Published: February 2011

Affective disorders (AFDs) are highly comorbid with substance dependence (SD) and both are genetically influenced. However, the specific etiology of the comorbidity is not well understood. We genotyped an array of 1,350 single nucleotide polymorphisms (SNPs) in or near 130 genes in 868 European‐Americans (EAs), including 182 individuals with primary AFDs (PAFDs), 214 with SD comorbid with AFD (CAFD), and 472 screened controls. NGFB, which encodes nerve growth factor β and was represented in the array by 15 SNPs, showed the strongest evidence of association, but only among women with PAFDs. Six of the SNPs showed nominally significant association with PAFDs in women (P's = 0.0007–0.01); three (rs2856813, rs4332358, and rs10776799) were empirically significant based on 1,000,000 permutations (P's = 0.008–0.015). Seven haplotypes were significantly associated with PAFDs in women (P's = 0.0014–0.01), of which six were significant based on empirical permutation analysis (minimal P = 0.0045). Four diplotypes were significantly associated with PAFDs in women (global P's = 0.001–0.01). The specific diplotype GG‐TC, reconstructed from rs2856813 and rs6678788, showed the strongest evidence of association with PAFDs in women (OR = 4.07, P = 4.2E−05). No SNPs or haplotypes were associated with PAFDs in men or with CAFDs in either sex. We conclude that variation in NGFB is a risk factor for PAFDs in women, but not for CAFD. © 2011 Wiley‐Liss, Inc.
Performance of reclassification statistics in comparing risk prediction models
Authors: Cook Nancy R. , Paynter Nina P.
Published: February 2011

Concerns have been raised about the use of traditional measures of model fit in evaluating risk prediction models for clinical use, and reclassification tables have been suggested as an alternative means of assessing the clinical utility of a model. Several measures based on the table have been proposed, including the reclassification calibration (RC) statistic, the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI), but the performance of these in practical settings has not been fully examined. We used simulations to estimate the type I error and power for these statistics in a number of scenarios, as well as the impact of the number and type of categories, when adding a new marker to an established or reference model. The type I error was found to be reasonable in most settings, and power was highest for the IDI, which was similar to the test of association. The relative power of the RC statistic, a test of calibration, and the NRI, a test of discrimination, varied depending on the model assumptions. These tools provide unique but complementary information.
Dysregulation of Claudin family genes in colorectal cancer in a Chinese population
Authors: Tang Weijun , Dou Tonghai , Zhong Ming , Wu Zhiyong
Published: February 2011

Claudins play an important role in tumor metastasis and in invasiveness of colorectal cancer (CRC). We have evaluated the relationship between CRC and expression of the claudin genes in Chinese patients with CRC. We measured CLDN1 and CLDN7 mRNA using quantitative PCR, and protein levels with immunohistochemistry in cancer tissues and adjacent normal tissue. Cancer tissues had significantly higher levels of CLDN1, and significantly lower levels of CLDN3, CLDN4, and CLDN7 than did normal tissue. CLDN3, CLDN4, and CLDN7 expression levels were higher in CRC of the protruded type than in CRC of the infiltrative type. Expression of CLDN7 correlated with lymph node metastasis. Stage N0 cancer tissues had higher levels of CLDN7 than did stages N1 and N2, suggesting that CLDN7 expression was closely related to the extent of lymph node metastasis. CLDN1 protein was upregulated, but CLDN7 protein was downregulated in cancer tissues when compared with expression in adjacent normal tissues. In conclusion, CLDN3, CLDN4, and CLDN7 were significantly downregulated, whereas CLDN1 was significantly upregulated in CRC. The altered expression of claudin genes may play a role in the initiation and development of CRC.
Synthesis and characterization of cyclic and linear helical poly(α‐peptoid)s by N‐heterocyclic carbene‐mediated ring‐opening polymerizations of N‐substituted N‐carboxyanhydrides
Authors: Guo Li , Li Jinhai , Brown Zachary , Ghale Kushal , Zhang Donghui
Published: February 2011

Cyclic poly(α‐peptoid)s [a.k.a. poly(N‐R‐glycine)] with chiral aromatic side‐chains [R = (R)‐ or (S)‐CHMePh] have been synthesized by N‐heterocyclic carbene‐mediated ring‐opening polymerization of N‐substituted N‐carboxyanhydrides (NR‐NCA). Their linear analogs have been prepared by primary amine‐initiated polymerization of the corresponding NR‐NCA. Poly[(R)/(S)‐N‐CHMePh‐glycine] with polymer molecular weights (MWs) in the range of 4–15 kg mol−1 and low MW distribution (Polydispersity index (PDI) < 1.15) can be readily accessed by these methods. Their high MW analogs were not obtained due to the competitive formation of cyclic oligomeric species that result from intramolecular transamidation. Intrinsic viscosity measurements confirm the architectural difference between the polymers prepared by the two methods and reveals that both cyclic and linear poly[(S)‐N‐CHMePh‐glycine]s behave as random‐coil polymers in 0.1M LiBr/Dimethylformamide (DMF) solution. Circular dichroism analysis suggests that the cyclic and linear poly(α‐peptoid)s retain polyproline I helix conformations, analogously to previously reported linear oligomers. Differential scanning calorimetry analysis reveals that cyclic and linear poly[(S)‐N‐CHMePh‐glycine] are both amorphous with the glass transition temperature of the cyclic polymers (Tg = 122°C) being notably higher than that of the linear analogs (Tg = 112°C) with identical MW. These results are consistent with the absence of chain ends, causing the polymers to have reduced segmental mobilities. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 596–603, 2011.
The unique plant RhoGAPs are dimeric and contain a CRIB motif required for affinity and specificity towards cognate small G proteins
Authors: Schaefer Antje , Höhner Kathrin , Berken Antje , Wittinghofer Alfred
Published: February 2011

Plant Rho proteins (ROPs) are inactivated by specific GTPase activating proteins, called RopGAPs. Many of these comprise the exclusive combination of a classic, catalytic Arg‐containing RhoGAP domain, and a Cdc42/Rac interactive binding (CRIB) motif which in animal and fungi has been identified in effectors for Cdc42 and Rac1, but never in any GAP protein. Both elements are required for an efficient RopGAP activity. Here, we analyzed the effect of the CRIB motif on the complex formation and the binding reaction with plant and human Rho proteins by using kinetic and equilibrium methods. We show that RopGAP2 from Arabidopsis thaliana dimerizes via its GAP domain and forms a 2:2 complex with ROP. The CRIB effector motif mediates high affinity and specificity in binding. The catalytic Arg in the context of the CRIB motif is inhibitory for binding. The unusually slow association and dissociation reactions suggest a major conformational change whereby the CRIB motif functions as a lid for binding and/or release of ROP. We propose a two‐site interaction model where ROP binds to the CRIB motif as described for the human CRIB effectors and to the catalytic GAP domain as described for animal RhoGAPs. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 420–433, 2011
Rapid determination of rifaximin on dried blood spots by LC‐ESI‐MS
Authors: Nageswara Rao R. , Vali R. Mastan , Ramachandra Bondigalla , Maurya Pawan K.
Published: February 2011

The use of blood spot collection cards is a simple way to obtain specimens for therapeutic drug monitoring, assessing adherence to medications and preventing toxicity in a clinical setting. A high‐throughput liquid chromatography–electrospray ionization mass spectrometric (LC‐ESI‐MS) method for determination of rifaximin on dried blood spots (DBS) was developed and validated. It involves solvent extraction of a punch of DBS followed by reversed‐phase LC on a monolithic column consisting of a silica rod with bimodal pore structure and detection by ESI‐MS. Rifampicin was used as an internal standard (IS). The run time was within 5.0 min with a very low back‐pressure at a flow rate of 0.5 mL/min. The assay was linear from 0.1 to 10 ng/mL. The mean recovery was 98.42%. The developed method is very simple, rapid and useful for clinical applications. Copyright © 2011 John Wiley & Sons, Ltd.
Effects of Acidity and Pore Size Constraints on Supported Niobium Oxide Catalysts for the Selective Formation of Glycerol Monolaurate
Authors: Radhakrishnan Rajitha , Wu Jiang , Jaenicke Stephan , Chuah Gaik Khuan
Published: February 2011

Supported niobium oxide catalysts with 5–30 wt. % Nb2O5 were prepared by grafting niobium ethoxide onto MCM‐41 and hydrous zirconia. The supported samples contain Brønsted‐acid sites, whereas bulk niobium oxide has predominantly Lewis‐acid sites. In the esterification of glycerol with lauric acid, good activity and a high glycerol monolaurate selectivity was achieved when the active niobium oxide phase was coated within the pore channels of an MCM‐41 support, which has a mean pore diameter of 2.2 nm. Phosphated Nb2O5/MCM‐41 showed an even higher activity without any penalty in selectivity, enabling monolaurate yields of 89–90 %. Glycerol monolaurate is an important ingredient in the food, pharmaceutical, and cosmetic industries. A key feature of these pore confined catalysts is the sustained high selectivity to monolaurate even at high conversions. In contrast, niobium oxide supported on wide‐pored hydrous zirconia showed lower selectivity. The catalysts are active in the solventless esterification of a number of alcohols and acids and can be easily recycled for subsequent batch reactions, making them attractive as green catalysts for sustainable processes.
γ‐ and δ‐Lactams through Palladium‐Catalyzed Intramolecular Allylic Alkylation: Enantioselective Synthesis, NMR Investigation, and DFT Rationalization
Authors: Bantreil Xavier , Prestat Guillaume , Moreno Aitor , Madec David , Fristrup Peter , Norrby Per‐Ola , Pregosin Paul S. , Poli Giovanni
Published: February 2011

The Pd‐catalyzed intramolecular allylic alkylation of unsaturated amides to give γ‐ and δ‐lactams has been studied in the presence of chiral ligands. Ligand (R)‐3,5‐tBu‐MeOBIPHEP (MeOBIPHEP=6,6’‐dimethoxybiphenyl‐2,2‐diyl)bis(diphenylphosphine)) afforded the best results and allowed the cyclization reactions to take place in up to 94:6 enantiomeric ratio. A model Pd–allyl complex has been prepared and studied through NMR spectroscopic analysis, which provided insight into the processes responsible for the observed enantiomeric ratios. DFT studies were used to characterize the diastereomeric reaction pathways. The calculated energy differences were in good agreement with the experimentally observed enantiomeric ratios.
Fluoride‐Cleavable, Fluorescently Labelled Reversible Terminators: Synthesis and Use in Primer Extension
Authors: Knapp Diana C. , Serva Saulius , D'Onofrio Jennifer , Keller Angelika , Lubys Arvydas , Kurg Ants , Remm Maido , Engels Joachim W.
Published: February 2011

Fluorescent 2′‐deoxynucleotides containing a protecting group at the 3′‐O‐position are reversible terminators that enable array‐based DNA sequencing‐by‐synthesis (SBS) approaches. Herein, we describe the synthesis and full characterisation of four reversible terminators bearing a 3′‐blocking moiety and a linker‐dye system that is removable under the same fluoride‐based treatment. Each nucleotide analogue has a different fluorophore attached to the base through a fluoride‐cleavable linker and a 2‐cyanoethyl moiety as the 3′‐blocking group, which can be removed by using a fluoride treatment as well. Furthermore, we identified a DNA polymerase, namely, RevertAid M‐MuLV reverse transcriptase, which can incorporate the four modified reversible terminators. The synthesised nucleotides and the optimised DNA polymerase were used on CodeLink slides spotted with hairpin oligonucleotides to demonstrate their potential in a cyclic reversible terminating approach.
Well‐Defined Air‐Stable Palladium HASPO Complexes for Efficient Kumada–Corriu Cross‐Couplings of (Hetero)Aryl or Alkenyl Tosylates
Authors: Ackermann Lutz , Kapdi Anant R. , Fenner Sabine , Kornhaaß Christoph , Schulzke Carola
Published: February 2011

Palladium complexes of representative heteroatom‐substituted secondary phosphine oxide (HASPO) preligands were synthesized and fully characterized, including X‐ray crystal structure analysis. Importantly, these well‐defined complexes served as highly efficient catalysts for Kumada–Corriu cross‐coupling reactions of aryl, alkenyl, and even heteroaryl tosylates. Particularly, an air‐stable catalyst derived from inexpensive PinP(O)H displayed a remarkably high catalytic efficacy, which resulted in cross‐couplings at low catalyst loadings under exceedingly mild reaction conditions with ample scope.
A Fully Conjugated TTF–π–TCAQ System: Synthesis, Structure, and Electronic Properties
Authors: Santos José , Illescas Beatriz M. , Martín Nazario , Adrio Javier , Carretero Juan C. , Viruela Rafael , Ortí Enrique , Spänig Fabian , Guldi Dirk M.
Published: February 2011

The synthesis of the first fully conjugated tetrathiafulvalene–tetracyano‐p‐quinodimethane ((TTF)–TCNQ)‐type system has been carried out by means of a Julia–Kocienski olefination reaction. In particular, a tetracyanoanthraquinodimethane (TCAQ) formyl derivative and two new sulfonylmethyl‐exTTFs (exTTF=2‐[9‐(1,3‐dithiol‐2‐ylidene)anthracen‐10(9H)‐ylidene]‐1,3‐dithiole)—prepared as new building blocks—were linked. A variety of experimental conditions reveal that the use of sodium hexamethyldisilazane (NaHMDS) as base in THF afforded the E olefins with excellent stereoselectivity. Theoretical calculations at the B3LYP/6‐31G** level point to highly distorted exTTF and TCAQ that form an almost planar stilbene unit between them. Although calculations predicted appreciable electronic communication between the donor and the acceptor, cyclic voltammetric studies did not substantiate this effect. It was only in photophysical assays that the electronic communication emerged in the form of a charge‐transfer (CT) absorption and emission. Once photoexcited (i.e., the locally excited state or excited charge‐transfer state), an ultrafast, subpicosecond charge separation leads to a radical ion pair state in which the spectroscopic features of the radical cation of exTTF as well as the radical anion of TCAQ are discernable. The radical ion pair is metastable and undergoes a fast ((1.0±0.2) ps) charge recombination to reconstitute the electronic ground state. Such ultrafast charge separation and recombination processes come as a consequence of the very short vinyl linkage between the two electroactive units.
ChemInform Abstract: Low Thermal Expansion Behavior and Electrical Conductivity of Mn3(Cu0.5SixGe0.5‐x)N at Low Temperatures.
Authors: Huang Rongjin , Wu Zhixiong , Chu Xinxin , Yang Huihui , Chen Zhen , Li Laifeng
Published: February 2011

The title compounds (x = 0.05, 0.1, 0.15, 0.2) are prepared by ball milling of mixtures of the elements followed by sintering (Ta foil, Ar, 850 °C, 48 h).
ChemInform Abstract: Preparation and Luminescence Properties of Green‐Light‐Emitting Afterglow Phosphor Ca8Mg(SiO4)4Cl2:Eu2+.
Authors: Lei Bingfu , Sha Lei , Zhang Haoran , Liu Yingliang , Man Shi‐qing , Yue Song
Published: February 2011

The title phosphor is synthesized by solid state reaction of Ca2SiO4:Eu2+ (obtained from CaCO3, SiO2, and Eu2O3 in alumina crucibles in a reducing 95%/5% N2/H2 gas flow at 1200 °C for 3 h), MgCl2, and NH4Cl as a flux (N2, 900 °C, 3 h).
ChemInform Abstract: Stabilization of a Complex Perovskite Superstructure under Ambient Conditions: Influence of Cation Composition and Ordering, and Evaluation as an SOFC Cathode.
Authors: Demont A. , Dyer M. S. , Sayers R. , Thomas M. F. , Tsiamtsouri M. , Niu H. N. , Darling G. R. , Daoud‐Aladine A. , Claridge J. B. , Rosseinsky M. J.
Published: February 2011

Ba1.6Ca2.3Y1.1Fe5O13 is an FeIII oxide with a complex perovskite superstructure, which is an intergrowth between the Ca2Fe2O5 and YBa2Fe3O8 structures featuring octahedral, square pyramidal, and tetrahedral B sites and three distinct A site environments.
ChemInform Abstract: A New Layered Indium Selenium Oxychloride Material: Synthesis, Structure, and Characterization of InSeO3Cl.
Authors: Lee Dong Woo , Ok Kang Min
Published: February 2011

The new title compound is synthesized as single phase by solid state reaction of a 1:1:3 mixture of In2O3, InCl3, and SeO2 (evacuated silica tube, 500 °C, 24 h).
ChemInform Abstract: High‐Pressure Synthesis and Crystal Structure of the New Holmium Oxoborate Ho31O27(BO3)3 (BO4)6.
Authors: Hering Stefanie A. , Haberer Almut , Kaindl Reinhard , Huppertz Hubert
Published: February 2011

The new title compound is synthesized in a modified Walker‐type module from a mixture of Ho2O3 and B2O3 (7.5—11.5 GPa, 1200 °C, 10 min).
ChemInform Abstract: Studies Regarding the Homogeneity Range of the Zirconium Phosphide Telluride Zr2+δPTe2.
Authors: Tschulik Kristina , Hoffmann Stefan , Fokwa Boniface P. T. , Gillessen Michael , Schmidt Peer
Published: February 2011

Single‐phase samples of the title compounds with 0 ≤ δ ≤ 1 are synthesized by solid state reaction of the elements (800 °C, 120 h).
ChemInform Abstract: A Facile Approach to Substituted Acrylates by Regioselective and Stereoselective Addition of Thiols and Amines to an Alkynyl Ester in Water.
Authors: Randive Nitin A. , Kumar Varun , Nair Vipin A.
Published: February 2011

A simple, efficient, and environmentally friendly reaction procedure for the stereoselective formation of thioacrylates and β‐enamino esters without employing any hazardous reagent or solvent is presented.