bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Policing in Comparison
Authors: Wisler Dominique , Onwudiwe Ihekwoaba D.
Published: June 2008

If community policing in Western democracies is often a unilateral action of the police promoting community self-rule, in most of the rest of the world, informal policing in communities is ubiquitous, popular, and sometimes excessive. Bracketing the Western ideology of community policing as state-initiated and -controlled (top-down) allows to discover a rich field of informal policing widely practiced by communities in Asia, Latin America, or Africa (bottom-up). Using secondary data as material, the article suggests accounting for these patterns of community policing with a state-centered model. Key variables identified by the authors are the service delivery capacity of the state, the dominant ideology, indirect or dual rule, political alliances as well as the framing of opportunites by civil society enterpreneurs or police managers, and available cultural repertoires of policing.
Review: Control of asthma
Authors: Zervas Eleftherios , Oikonomidou Erasmia , Kainis Elias , Kokkala Marietta , Petroheilou Kalomira , Gaga Mina
Published: June 2008

Control is the aim of asthma management and clinical trials show that control can be achieved in the majority of patients. However, population surveys show that poorly controlled asthma still imposes a considerable burden. This fact has led to a re-evaluation of the international asthma guidelines and the updated 2006 and 2007 GINA and NAEPP guidelines suggest that the level of control should be used as the key feature for the classification and management of asthma. Furthermore, in the latest guidelines, a clearer definition of control is given and new tools for the assessment and monitoring of control are instituted. In order to achieve asthma control, not only relevant pharmacological treatment but, the establishment of a good patient-doctor relationship, proper education of the asthmatic patient, reduction of exposure to triggers and treatment of co-morbidities are pivotal issues and must be ensured.
A Study of the Validity of Performing Carotid Duplex Ultrasound with the Patient in a Seated Position
Authors: Pemble Lucia
Published: June 2008

Objective: The purpose of this study was to compare pulsed wave (PW) Doppler velocity measurements obtained from duplex ultrasound of the carotid arteries with subjects in the seated and supine positions in an attempt to determine if this would influence the velocity criteria used in the classification of the severity of internal carotid artery disease.

Methods: Carotid duplex ultrasound examinations were performed on 42 volunteers with measurement of peak systolic velocities (PSV) and end diastolic velocities (EDV) using a Doppler angle of 60°. The measurements were obtained from both the right and left extracranial carotid vessels in both the seated and supine positions. t-tests were used to compare the mean velocities obtained in the seated versus supine positions.

Results: PSV and EDV measurements obtained in the seated position were lower than those in the supine position. Statistical analysis comparing the means in the seated versus the supine position showed statistical significance at the p=0·05 level for all measurements except the PSV of the internal carotid artery (ICA).

Conclusions: Duplex ultrasound PW Doppler derived velocity criteria are used to classify the severity of stenosis, which in turn impacts on patient treatment options. The carotid duplex scan can be adequately performed on patients in the seated position but velocities measured will be reduced and modification to the existing velocity criteria may be needed.
Bedside Sonography in Emergency Departments in Turkey
Authors: Girisgin Sadik A. , Cander Basar , Yurumez Yusuf , Coskun Figen , Ikizceli Ibrahim , Akkose Sule
Published: June 2008

Emergency departments in Turkey have been steadily improving their services since emergency medicine began as a specialty over 12 years ago, but bedside ultrasound (US) has not been implemented widely. In order to learn the extent of ultrasound usage and training opportunities, a 27-question survey was distributed to emergency medicine-trained physicians working in emergency departments at ten university hospitals (the busiest one in each geographical region, plus three others), which are referral centres covering over half of the country's population.

Eight of the ten EM departments had an ultrasound machine in their ED (for a mean of 3·7 years), but the machines were used and controlled by the Department of EM in only four of the centres. While EM physicians knew how to perform US in seven centres, they routinely performed US themselves in only five. Of the 173 EM staff in the centres surveyed, 57 performed bedside US, and 28 possessed an US course certificate. All respondents wanted their EM residents to have formal US training, but such a rotation was present in only five centres. Bedside US was being performed in the following clinical situations: trauma (n=7), abdominal pain (n=7), renal colic (n=5), chest pain (n=3), assist to invasive procedures (n=3), locating subcutaneous foreign bodies (n=3), and dyspnea (n=1). Five departments had no form or system for documenting their US findings, and if finding anything suspicious, always sent the patients to radiology to have the US repeated. The mean duration from request-to-radiology-for-US to report-in-EM-physician's-hands was 47 minutes.

Bedside US is performed by EM physicians in only half of the academic centers we surveyed. Documentation is absent in many, thus the quality or impact of this practice would be difficult, if not impossible, to determine. Formal educational programs are desired by all, but have yet to be implemented in half of the centres. Given the many benefits to patients of bedside US, diligent efforts still need to be made to improve this service in academic emergency departments in Turkey.
Microstructure of Al–Mg dissimilar weld made by cold metal transfer MIG welding
Authors: Wang J. , Feng J. C. , Wang Y. X.
Published: June 2008

A modified metal inert gas welding process called cold metal transfer was successfully applied to dissimilar Mg and Al welding with AlSi5 filler metal. Optical microscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction were used to characterise the microstructure, alloy element distribution and phase constituents of the welded joint. The microhardness distribution was determined by microhardness tester on the fusion zone. The super low heat input and the addition of Si inhibited the creation and growth of brittle intermetallic compound in weld metal, which improved the strength of the joint. An obvious multilayer microstructure, which comprised of solid solution, eutectic structure, Mg17Al12, and Mg2Al3 layer, was observed in the fusion zone adjacent to the Mg substrate. It degraded the strength, leading to the fracture of the joint in tensile test. The fracture morphology presented the typical brittleness fracture mode.
Acicular ferrite development in autogenous laser welds using cerium sulphide particle dispersed steels
Authors: Thewlis G. , Chao W. T. , Harrison P. L. , Rose A. J.
Published: June 2008

Acicular ferrite development has been investigated in autogenous laser welds using cerium sulphide particle dispersed steels. Around 80% acicular ferrite has been obtained in weld metal irrespective of [Al]/[O] ratio. Acicular ferrite is high when combined sulphur and oxygen levels are between 200 and 550 ppm, but is markedly reduced below 200 ppm. Large acicular ferrite variations cannot be explained by changes in particle number density and austenite grain size, but may be attributed to changes in particle type. Phases promoting high acicular ferrite are (Ce,La)2O2S, Ce4O4S3, MnS and TiN, with some Al2O3, CeAlO3 and rare earth sulphides. Reduced acicular ferrite results from an absence of TiN or MnS. It is argued that phases may radically influence acicular ferrite content by altering the thermodynamic driving force for intragranular transformation and varying nucleation and growth kinetics through epitaxial relationships. Where aluminium is the primary deoxidising agent, loss of acicular ferrite at [Al]/[O] ratios greater than unity may potentially be explained by unfavourable Al2O3 clustering and formation of eutectic type II MnS colonies. When cerium is the primary deoxidising and desulphurising agent, this is not observed.
CD300a/c regulate type I interferon and TNF-α secretion by human plasmacytoid dendritic cells stimulated with TLR7 and TLR9 ligands
Authors: Ju Xinsheng , Zenke Martin , Hart Derek N. J. , Clark Georgina J.
Published: June 2008

Activation of human plasmacytoid dendritic cells (pDCs) with ligands for Toll-like receptors (TLRs) 7 and 9 induces the secretion of type I interferons and other inflammatory cytokines as well as pDC differentiation. Transcripts for 2 members of the CD300 gene family, CD300a and CD300c, were identified on pDCs during gene expression studies to identify new immunoregulatory molecules on pDCs. We therefore investigated the expression of CD300a and CD300c and their potential regulation of pDC function. CD300a/c RNA and surface expression were downregulated after stimulation of pDCs with TLR7 and TLR9 ligands. Exogenous interferon (IFN)-α down-regulated CD300a/c expression, whereas neutralizing IFN-α abolished TLR ligand–induced CD300a/c down-regulation. This implicates IFN-α in regulating CD300a/c expression in pDCs. In addition, IFN-α favored tumor necrosis factor (TNF)-α secretion by CpG-induced pDCs. CD300a/c triggering by cross-linking antibody reduced TNF-α and increased IFN-α secretion by pDCs. Furthermore, CD300a/c triggering, in the presence of neutralizing IFN-α, further reduced TNF-α secretion. These data indicate that CD300a and CD300c play an important role in the cross-regulation of TNF-α and IFN-α secretion from pDCs.
Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders
Authors: Higgins John M. , Sloan Steven R.
Published: June 2008

Red blood cell (RBC) transfusion is unique as a common large-scale intravenous introduction of foreign tissue and provides a valuable opportunity to study human immunologic response to intravenous foreign antigen. Patients receiving RBC transfusions are at risk of forming alloantibodies against donor RBC antigens, and valid estimates of alloimmunization risk are clinically important, but little is known about the factors governing this risk or, more generally, about determinants of human response to intravenous antigen. Here, we mine large electronic patient databases enabling us to model RBC alloimmunization as a stochastic process. We identify a subgroup of transfusion recipients that has a dramatically increased risk of alloimmunization that appears to be genetically determined because it is independent of common disease states, patient age, or the number of alloantibodies already formed, and only weakly dependent on transfusion count.
Gene expression in developing watermelon fruit
Authors: Wechter W Patrick , Levi Amnon , Harris Karen R , Davis Angela R , Fei Zhangjun , Katzir Nurit , Giovannoni James J , Salman-Minkov Ayelet , Hernandez Alvaro , Thimmapuram Jyothi , Tadmor Yaakov , Portnoy Vitaly , Trebitsh Tova
Published: June 2008

Background

Cultivated watermelon form large fruits that are highly variable in size, shape, color, and content, yet have extremely narrow genetic diversity. Whereas a plethora of genes involved in cell wall metabolism, ethylene biosynthesis, fruit softening, and secondary metabolism during fruit development and ripening have been identified in other plant species, little is known of the genes involved in these processes in watermelon. A microarray and quantitative Real-Time PCR-based study was conducted in watermelon [Citrullus lanatus(Thunb.) Matsum. & Nakai var. lanatus] in order to elucidate the flow of events associated with fruit development and ripening in this species. RNA from three different maturation stages of watermelon fruits, as well as leaf, were collected from field grown plants during three consecutive years, and analyzed for gene expression using high-density photolithography microarrays and quantitative PCR.

Results

High-density photolithography arrays, composed of probes of 832 EST-unigenes from a subtracted, fruit development, cDNA library of watermelon were utilized to examine gene expression at three distinct time-points in watermelon fruit development. Analysis was performed with field-grown fruits over three consecutive growing seasons. Microarray analysis identified three hundred and thirty-five unique ESTs that are differentially regulated by at least two-fold in watermelon fruits during the early, ripening, or mature stage when compared to leaf. Of the 335 ESTs identified, 211 share significant homology with known gene products and 96 had no significant matches with any database accession. Of the modulated watermelon ESTs related to annotated genes, a significant number were found to be associated with or involved in the vascular system, carotenoid biosynthesis, transcriptional regulation, pathogen and stress response, and ethylene biosynthesis. Ethylene bioassays, performed with a closely related watermelon genotype with a similar phenotype, i.e. seeded, bright red flesh, dark green rind, etc., determined that ethylene levels were highest during the green fruit stage followed by a decrease during the white and pink fruit stages. Additionally, quantitative Real-Time PCR was used to validate modulation of 127 ESTs that were differentially expressed in developing and ripening fruits based on array analysis.

Conclusion

This study identified numerous ESTs with putative involvement in the watermelon fruit developmental and ripening process, in particular the involvement of the vascular system and ethylene. The production of ethylene during fruit development in watermelon gives further support to the role of ethylene in fruit development in non-climacteric fruits.
This issue of GEOPHYSICS
Authors: Wapenaar Kees
Published: June 2008

In this article, the Editor of Geophysics provides an overview of all technical articles in this issue of the journal.
Gastric Cancer Stem Cells
Authors: Takaishi Shigeo , Okumura Tomoyuki , Wang Timothy C.
Published: June 2008

Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony formation in serum-free media in vitro, as well as tumorigenic ability in immunodeficient mice in vivo. We will also discuss the possible origins of the gastric cancer stem cell from an organ-specific stem cell versus a recently recognized new candidate bone marrow–derived cell (BMDC). We have previously shown that BMDC contributed to malignant epithelial cells in the mouse model of Helicobacter-associated gastric cancer. On the basis of these findings from animal model, we propose that a similar phenomenon may also occur in human cancer biology, particularly in the cancer origin of other inflammation-associated cancers. The expanding research field of cancer stem-cell biology may offer a novel clinical apparatus to the diagnosis and treatment of cancer.
Liver Cancer Stem Cells
Authors: Sell Stewart , Leffert Hyam L.
Published: June 2008

In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.
Chronic Myeloid Leukemia Stem Cells
Authors: Kavalerchik Edward , Goff Daniel , Jamieson Catriona H.M.
Published: June 2008

Although rare, chronic myeloid leukemia (CML) represents an important paradigm for understanding the molecular events leading to malignant transformation of primitive hematopoietic progenitors. CML was the first cancer to be associated with a defined genetic abnormality, BCR-ABL, that is necessary and sufficient for initiating chronic phase disease as well as the first cancer to be treated with molecular targeted therapy. Malignant progenitors or leukemia stem cells (LSCs) evolve as a result of both epigenetic and genetic events that alter hematopoietic progenitor differentiation, proliferation, survival, and self-renewal. LSCs are rare and divide less frequently, and thus, represent a reservoir for relapse and resistance to a molecularly targeted single agent. On subverting developmental processes normally responsible for maintaining robust life-long hematopoiesis, the LSCs are able to evade the majority of current cancer treatments that target rapidly dividing cells. Enthusiasm for the enormous success of tyrosine kinase inhibitors at controlling the chronic phase disease is tempered somewhat by the persistence of the LSC pool in the majority of the patients. Combined therapies targeting aberrant properties of LSC may obviate therapeutic resistance and relapse in advanced phase and therapeutically recalcitrant CML.
Impaired β-Cell Function and Inadequate Compensatory Increases in β-Cell Mass after Intrauterine Growth Restriction in Sheep
Authors: Gatford Kathryn L. , Mohammad Saidatul N. B. , Harland M. Lyn , De Blasio Miles J. , Fowden Abigail L. , Robinson Jeffrey S. , Owens Julie A.
Published: June 2008

Poor growth before birth increases the risk of non-insulin-dependent diabetes mellitus (NIDDM) and impairs insulin secretion relative to sensitivity. We investigated the effects of intrauterine growth restriction in sheep on insulin secretion, β-cell mass, and function from before birth to young adulthood and its molecular basis. Pancreas was collected from control and placentally restricted sheep as fetuses (d 143 gestation), lambs (aged 42 d), and young adults (aged 556 d), following independent measures of in vivo insulin secretion and sensitivity. β-Cells and islets were counted after immunohistochemical staining for insulin. In lambs, gene expression was measured by RT-PCR and expressed relative to 18S. β-Cell mass correlated positively with fetal weight but negatively with birth weight in adult males. Glucose-stimulated insulin disposition and β-cell function correlated negatively with fetal weight but positively with birth weight in adult males. Placental restriction increased pancreatic expression of IGF-II and IGF-I but decreased that of voltage-gated calcium channel, α1D subunit (CACNA1D) in lambs. In male lambs, pancreatic IGF-II and insulin receptor expression correlated strongly and positively with β-cell mass and CACNA1D expression with glucose-stimulated insulin disposition. Restricted growth before birth in the sheep does not impair insulin secretion, relative to sensitivity, before birth or in young offspring. IGF-II and insulin receptor are implicated as key molecular regulators of β-cell mass compensation, whereas impaired expression of the voltage-gated calcium channel may underlie impaired β-cell function after intrauterine growth restriction. With aging, the insulin secretory capacity of the β-cell is impaired in males, and their increases in β-cell mass are inadequate to maintain adequate insulin secretion relative to sensitivity.
A New Organotypic Culture of Adipose Tissue Fragments Maintains Viable Mature Adipocytes for a Long Term, Together with Development of Immature Adipocytes and Mesenchymal Stem Cell-Like Cells
Authors: Sonoda Emiko , Aoki Shigehisa , Uchihashi Kazuyoshi , Soejima Hidenobu , Kanaji Sachiko , Izuhara Kenji , Satoh Seiji , Fujitani Noboru , Sugihara Hajime , Toda Shuji
Published: June 2008

Adipose tissue that consists of mature and immature adipocytes is suggested to contain mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. Here we show that three-dimensional collagen gel culture of rat sc adipose tissue fragments maintained viable mature adipocytes for a long term, producing immature adipocytes and MSC-like cells from the fragments, using immunohistochemistry, ELISA, and real time RT-PCR. Bromodeoxyuridine uptake of mature adipocytes was detected. Adiponectin and leptin, and adipocyte-specific genes of adiponectin, leptin, and PPAR-γ were detected in culture assembly, whereas the lipogenesis factor insulin (20 mU/ml) and inflammation-related agent TNF-α (2 nm) increased and decreased, respectively, all of their displays. Both spindle-shaped cell types with oil red O-positive lipid droplets and those with expression of MSC markers (CD105 and CD44) developed around the fragments. The data indicate that adipose tissue-organotypic culture retains unilocular structure, proliferative ability, and some functions of mature adipocytes, generating both immature adipocytes and CD105+/CD44+ MSC-like cells. This suggests that our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome.
Antecedents of IS Strategic Alignment: A Nomological Network
Authors: Preston David S. , Karahanna Elena
Published: June 2008

Alignment of information systems (IS) strategy with business strategy is a top concern of both the chief information officer (CIO) and the top management team (TMT) of organizations. Even though researchers and key decision makers in organizations recognize the importance of IS strategic alignment, they often struggle to understand how this alignment is created. In this paper, we develop a nomological network in which shared understanding between the CIO and TMT about the role of IS in the organization (which represents the social dimension of IS strategic alignment) is posited to be a proximal antecedent of the intellectual dimension of IS strategic alignment. We further posit that shared language, shared domain knowledge manifest in the CIO's business knowledge and the TMT's strategic IS knowledge, systems of knowing (structural and social), and CIO-TMT experiential similarity are important determinants of this shared understanding. Data were collected from 243 matched CIO-TMT pairs. Results largely support the proposed nomological network. Specifically, shared understanding between the CIO and TMT is a significant antecedent of IS strategic alignment. Furthermore, shared language, shared domain knowledge, and structural systems of knowing influence the development of shared understanding between the CIO and the TMT. Contrary to expectations and to findings of prior research, social systems of knowing, representing informal social interactions between the CIO and TMT, and experiential similarity did not have a significant effect on shared understanding.
Simulated joint and muscle forces in reversed and anatomic shoulder prostheses
Authors: Terrier A. , Reist A. , Merlini F. , Farron A.
Published: June 2008

Reversed shoulder prostheses are increasingly being used for the treatment of glenohumeral arthropathy associated with a deficient rotator cuff. These non-anatomical implants attempt to balance the joint forces by means of a semi-constrained articular surface and a medialised centre of rotation. A finite element model was used to compare a reversed prosthesis with an anatomical implant. Active abduction was simulated from 0° to 150° of elevation. With the anatomical prosthesis, the joint force almost reached the equivalence of body weight. The joint force was half this for the reversed prosthesis. The direction of force was much more vertically aligned for the reverse prosthesis, in the first 90° of abduction. With the reversed prosthesis, abduction was possible without rotator cuff muscles and required 20% less deltoid force to achieve it.

This force analysis confirms the potential mechanical advantage of reversed prostheses when rotator cuff muscles are deficient.
Results of the Birmingham Hip Resurfacing dysplasia component in severe acetabular insufficiency
Authors: McMinn D. J. W. , Daniel J. , Ziaee H. , Pradhan C.
Published: June 2008

The dysplasia cup, which was devised as an adjunct to the Birmingham Hip Resurfacing system, has a hydroxyapatite-coated porous surface and two supplementary neutralisation screws to provide stable primary fixation, permit early weight-bearing, and allow incorporation of morcellised autograft without the need for structural bone grafting.

A total of 110 consecutive dysplasia resurfacing arthroplasties in 103 patients (55 men and 48 women) performed between 1997 and 2000 was reviewed with a minimum follow-up of six years. The mean age at operation was 47.2 years (21 to 62) and 104 hips (94%) were Crowe grade II or III.

During the mean follow-up of 7.8 years (6 to 9.6), three hips (2.7%) were converted to a total hip replacement at a mean of 3.9 years (2 months to 8.1 years), giving a cumulative survival of 95.2% at nine years (95% confidence interval 89 to 100). The revisions were due to a fracture of the femoral neck, a collapse of the femoral head and a deep infection. There was no aseptic loosening or osteolysis of the acetabular component associated with either of the revisions performed for failure of the femoral component. No patient is awaiting a revision.

The median Oxford hip score in 98 patients with surviving hips at the final review was 13 and the 10th and the 90th percentiles were 12 and 23, respectively.
Schwannoma of the fibula
Authors: Palocaren T. , Walter N. M. , Madhuri V. , Gibikote S.
Published: June 2008

We describe a schwannoma located in the mid-diaphyseal region of the fibula of a 14-year-old boy. Radiologically this was an expansile, lytic, globular and trabeculated lesion. MRI showed a narrow transition zone with a break in the cortex and adjacent tissue oedema. Differential diagnosis included schwannoma, fibrous dysplasia, giant cell tumour and aneurysmal bone cyst. The tumour was excised en bloc, with marginal resection limits, and there has been no recurrence two years after surgery. Histopathological examination confirmed the diagnosis of classic schwannoma. There were typical hypercellular Antoni A zones, less cellular Antoni B zones, and diffuse immunoreactivity to S100 protein. This is the first report of schwannoma involving a long bone in a child.
Trends in Mathematics and Science Study (TIMSS): International Accountability and Implications for Science Instruction
Authors: Eckert Jonathan M.
Published: June 2008

International educational comparisons are relatively recent phenomena and have long been the source of international debate. Since the formation of the International Association for the Evaluation of Educational Achievement (IEA) in the 1950s, assessments have grown increasingly more valid and reliable. TIMSS is an exemplary attempt at cross-national comparison. In trying to link results to practice, TIMSS released video studies that attempt to compare teaching methodologies employed in science in various countries. Much has been made of the TIMSS report and the pedagogy displayed in the video studies, but one question remains unanswered. What are the implications for science instruction based on cross-national comparisons? In countries such as the USA and the United Kingdom, the TIMSS reports have been the basis of much criticism of science instruction. This article explores the implications of the TIMSS reports and offers recommendations for the use of cross-national comparisons to impact classroom instruction.
Identification of Endocrine-Disrupting Compounds Using Nanoelectrospray Ionization Mass Spectrometry
Authors: Bovet Cédric , Ruff Marc , Wortmann Arno , Eiler Sylvia , Granger Florence , Gerrits Bertran , Moras Dino , Zenobi Renato
Published: June 2008

A method using chip-based nanoelectrospray mass spectrometry (nanoESI-MS) is described to detect noncovalent ligand binding to the human estrogen receptor alpha ligand-binding domain (hER? LBD). This system represents an important environmental interest, because a wide variety
of molecules, known as endocrine-disrupting compounds (EDCs), can bind to the estrogen receptor (ER) and induce adverse health effects in wildlife and humans. An efficient analytical method is therefore required to identify EDCs and characterize their solution-phase binding affinity and character
(i.e. agonist or antagonist). Using proper experimental conditions, the nanoESI-MS approach allowed the detection of specific ligand interactions with hER? LBD. The best approach to evaluate solution-binding affinity by nanoESI-MS was to perform competitive binding experiments
with 17?-estradiol (E2) as a reference ligand. Among the ligands tested, the relative binding affinity for hER? LBD measured by nanoESI-MS was 4-hydroxytamoxifen ? diethylstilbestrol > E2 ? genistein ? bisphenol A, consistent with the order of the binding affinities
in solution. To discern agonist from antagonist, we used the specificity of a coactivator peptide for agonist-bound receptor. A specific coactivator-hER? LBD complex was detected only in the presence of an agonist ligand. Therefore, the specificity of nanoESI-MS combined with its speed
(1 min/ligand), low sample consumption (90 pmol protein/ligand), and its sensitivity for ligand (30 ng/ml) demonstrates that this method is promising for the identification and characterization of suspected ER ligands in a high-throughput manner.
Gonadal Malformations in Whitefish from Lake Thun: Defining the Case and Evaluating the Role of EDCs
Authors: Bernet Daniel , Wahli Thomas , Suter Marc J.-F. , Largiader Carlo R. , Küng Christoph , Kipfer Sibylle , Eggen Rik I. L. , Bittner David , Liedtke Anja , Segner Helmut
Published: June 2008

The objectives of this project were to evaluate i) whether the gonad alterations of whitefish (Coregonus lavaretus spp.) in Lake Thun represent abnormal morphological variations specific to this lake, and, if so, ii) whether the malformations are related to chemical exposure,
in particular to exposure to endocrine-disrupting compounds (EDCs). Large-scale monitoring data revealed that, although whitefish in other lakes display some background variation of gonad morphology, the situation in Lake Thun, is unique because of the significantly higher prevalence of gonad
malformations. The abnormal variations of whitefish gonad morphology include aplasias, compartmentations, fusions, and intersex. In the search for the factor(s) causing the gonad malformations, coregonids were exposed from fertilization up to maturity to Lake Thun water and plankton or to
contaminants possibly being present in the lake, including trinitrotoluenes, and naphtalene sulfonates. Since these experiments are still ongoing, a conclusive answer cannot be given yet, but initial observations point to a role of the lake plankton. The possible presence of EDCs in Lake Thun
was assessed using bioanalytics and biomarkers. The bioanalytical studies found estrogenic activities in concentrated plankton extracts of Lake Thun, however, estrogenic activities occurred also in plankton extracts of reference lakes. Bioassay-directed fractionation of the plankton samples
points to degradation products of natural substances as a cause of the estrogenic activity. Examination of Lake Thun whitefish for EDC biomarkers such as vitellogenin, sex steroid levels or intersex frequency yielded no indications of exposure to EDCs, neither in fish with normal nor in fish
with abnormal gonad morphology. Long-term laboratory exposure of developing coregonids to the prototype estrogenic compound, 17?-estradiol, resulted in an increased frequency of intersex gonads, but did not induce the other gonad malformations typical for Lake Thun coregonids. In summing
up, the currently available evidence does not support an EDC or chemical etiology of the gonad malformations, however, this preliminary conclusion needs to be substantiated in the ongoing investigations. The project also highlights the need for more detailed knowledge of natural variation
in wildlife populations to be able to recognize anthropogenically caused variation.
Diethylstilbestrol Action on Leydig Cell Function and Testicular Descent
Authors: Cederroth Christopher R. , Nef Serge
Published: June 2008

Exposure to environmental chemicals may adversely affect the endocrine system and male sexual development. Testicular descent is regulated hormonally by Leydig-cell derived testosterone and Insulin-like factor 3 (Insl3). While Insl3 is required for transabdominal descent by stimulating
the contraction and growth of the gubernaculum, testosterone contributes to the involution of the suspensory ligament and mediates the inguinoscrotal phase of the descent. In rodents, prenatal exposure to estradiol or xenoestrogens such as diethylstilbestrol (DES) leads to cryptorchidism and
is associated with a downregulation of Insl3 transcription. In this review, we summarize the molecular and endocrine events responsible for testicular descent and how fetal exposure to xenoestrogens can adversely affect it. Recent data suggest that in utero exposure to DES affects fetal
Leydig cell endocrine functions, more precisely the steroidogenic function, Insl3 expression and testicular descent, via an ER?-dependent mechanism. The expression of Leydig-specific genes such as Insl3, Cyp17a1, Star and Renin1 were profoundly decreased upon exposure to E2 or
DES but not affected in mutant testes lacking ER?. Whether these effects of ER? are mediated via its classical mode of action or through a non-genomic action remains unclear. Unraveling the molecular events inhibiting the endocrine functions of fetal Leydig cells through
an ER?-dependent mechanism will provide important insights into the adverse effects of estrogenic exposure on the male urogenital system and testicular descent.
Results of the Consensus Platforms: Positions and Recommendations Derived from Scientific Findings in a Joint Effort of Academics, Industry, and Authorities
Authors: Trachsel Marcel
Published: June 2008

To convert scientific findings of the National Research Program (NRP) 'Endocrine Disruptors' into political and practical action the innovative tool of the consensus platforms has been created. The consensus platforms brought together representatives of the NRP, of the authorities and
industry. They prepared generally accepted positions on the effects of endocrine disruptors and recommendations on actions to be taken to minimize these effects. This article shows the positions and recommendations of all three consensus platforms.
Activation of Hypoxic Response in Human Embryonic Stem Cell–Derived Embryoid Bodies
Authors: Cameron C. M. , Harding Frances , Hu Wei-Shou , Kaufman Dan S.
Published: June 2008

Oxygen tension can provide an important determinant for differentiation and development of many cells and tissues. Genetic regulation of hemato-endothelial commitment is known to respond to oxygen deprivation via stimulation of hypoxia inducible factors (HIFs). Here, we use a closed bioreactor system to monitor and control the dissolved oxygen during differentiation of human embryonic stem cells (hESCs) via formation of embryoid bodies (hEBs). Exposing hESC-derived EBs to ambient oxygen at or below 5% results in stabilization of HIF-1α and increased transcription of hypoxic responsive genes. Interestingly, we find that rather than HIF-1α expression being stable over prolonged (7–16 days) culture in hypoxic conditions, HIF-1α expression peaks after approximately 48 hours of hypoxic exposure, and then declines to near undetectable levels, despite constant hypoxic exposure. This transient stabilization of HIF-1α during hESC-derived EB culture is demonstrated for four distinct stages of differentiation. Furthermore, we demonstrate hEB cell expansion is slowed by hypoxic exposure, with increased apoptosis. However, hEB cell proliferation returns to normal rates upon return to normoxic conditions. Therefore, although hypoxia effectively stimulates hypoxic responsive genes, this single variable was not sufficient to improve development of hemato-endothelial cells from hESCs.
Cardiac Glucose Uptake and Suppressed Expression/Translocation of Myocardium Glucose Transport-4 in Dogs Undergoing Ischemia-Reperfusion
Authors: Liang Gui-You , Cai Qing-Yong , Niu Yi-Ming , Zheng Hong , Gao Zhen-Yu , Liu Da-Xing , Xu Gang
Published: June 2008

Impaired glucose metabolism is implicated in cardiac failure during ischemia-reperfusion. This study examined cardiac glucose uptake and expression of glucose transport-4 (GLUT-4) in dogs undergoing ischemia-reperfusion. Cardiac ischemia was induced by cardiopulmonary bypass for 30 min or 120 min in dogs. Plasma insulin and glucose concentrations were measured at pre-bypass (control), and aortic cross-clamp off (ischemia-reperfusion) at 15, 45, and 75 min. At the same time, the left ventricle biopsies were taken for GLUT-4 immunohistochemistry and glycogen content analysis. In dogs receiving 120-min ischemia, coronary arterial and venous glucose concentrations were increased, but the net glucose uptake in ischemia-reperfusion heart were significantly decreased from 25% (control) to zero at 15 and 45 min of reperfusion, and recovered to only 7% after 75 min reperfusion. Myocardium glycogen contents were decreased by 65%. Plasma insulin levels and Insulin Resistant Index were markedly increased in dogs undergoing 120-min ischemia and reperfusion. These changes were relatively mild and reversible in dogs receiving only 30-min ischemia followed by reperfusion. Expression of total GLUT-4 in myocardium was decreased 40% and translocation of GLUT-4 from cytoplasm to surface membrane was decreased 90% in dogs receiving 120-min ischemia followed by 15-min reperfusion. Suppressed translocation of GLUT-4 was also evident in dogs receiving 30-min ischemia, but to a lesser extent. Reduced myocardium glucose uptake, utilization, and glycogen content are clearly associated with ischemia-reperfusion heart injury. This appears to be due, at least in part, to suppressed expression and translocation of myocardium GLUT-4.
Reinforcement of maleated natural rubber by precipitated silica
Authors: Sahakaro Kannika , Beraheng Sumsuriya
Published: June 2008

Graft copolymers of maleic anhydride and natural rubber or so‐called maleated natural rubbers (MNRs) were prepared in a molten state with varying maleic anhydride contents from 4 to 10 phr. In this work, the filler–filler and filler–rubber interactions of the MNR and precipitated silica were investigated. The MNR compounds containing 40 phr of silica both with and without 9 wt % of silane coupling agent were prepared. By increasing the maleic anhydride contents, the Mooney viscosity and cure times were increased, but the torque differences and cure rate indices were decreased. Bound rubber was increased with increasing maleic anhydride content, indicating an increase of filler–rubber interaction. In case of the compounds without silane, the MNR with 6 phr of maleic anhydride showed the lowest filler–filler interaction as indicated by a decrease of storage modulus upon an increase of strain in the filled compound i.e., Payne effect. This MNR compound also yielded the optimum mechanical properties. It has been demonstrated that a use of MNR with appropriate maleic anhydride content can reduce filler–filler interaction dramatically and hence improve a silica dispersion, as confirmed by SEM micrographs, resulting in an enhancement of the mechanical and dynamical properties. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Improvement in the flame retardancy of cotton fabric by admicellar polymerization of 2‐acryloyloxyethyl diethyl phosphate using an anionic surfactant
Authors: Siriviriyanun Ampornphan , O'Rear Edgar A. , Yanumet Nantaya
Published: June 2008

The phosphorus‐containing acrylate monomer, 2‐acryloyloxyethyl diethyl phosphate (ADEP), was synthesized and applied to cotton fabric by using admicellar polymerization. Sodium dodecylbenzene sulfonate was used as the anionic surfactant. The film of polymerized monomer (PADEP) formed on the cotton surface was characterized by FTIR‐ATR spectroscopy and SEM. Thermal and flame retardant properties of PADEP‐coated cotton were investigated by TGA and flammability tests. Results showed that PADEP polymer film was successfully formed on the cotton fabric. The TGA and DTG analyses showed that the phosphorus‐containing PADEP lowered the decomposition temperature of the treated fabric resulting in a higher char yield than in the case of untreated cotton. The flammability tests showed that the treated cotton had much improved flame retardancy property after the treatment. The treated fabric also retained its good pliability and soft touch with good air permeability. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Authors' reply
Authors: Groothuis‐Oudshoorn C. G. M. , Miedema H. M. E.
Published: June 2008

Article: http://dx.doi.org/10.1002/bimj.200410172

Letter to the Editor: http://dx.doi.org/10.1002/bimj.200710416
Imputation Strategies for Missing Continuous Outcomes in Cluster Randomized Trials
Authors: Taljaard Monica , Donner Allan , Klar Neil
Published: June 2008

In cluster randomized trials, intact social units such as schools, worksites or medical practices – rather than individuals themselves – are randomly allocated to intervention and control conditions, while the outcomes of interest are then observed on individuals within each cluster. Such trials are becoming increasingly common in the fields of health promotion and health services research. Attrition is a common occurrence in randomized trials, and a standard approach for dealing with the resulting missing values is imputation. We consider imputation strategies for missing continuous outcomes, focusing on trials with a completely randomized design in which fixed cohorts from each cluster are enrolled prior to random assignment. We compare five different imputation strategies with respect to Type I and Type II error rates of the adjusted two‐sample t ‐test for the intervention effect. Cluster mean imputation is compared with multiple imputation, using either within‐cluster data or data pooled across clusters in each intervention group. In the case of pooling across clusters, we distinguish between standard multiple imputation procedures which do not account for intracluster correlation and a specialized procedure which does account for intracluster correlation but is not yet available in standard statistical software packages. A simulation study is used to evaluate the influence of cluster size, number of clusters, degree of intracluster correlation, and variability among cluster follow‐up rates.

We show that cluster mean imputation yields valid inferences and given its simplicity, may be an attractive option in some large community intervention trials which are subject to individual‐level attrition only; however, it may yield less powerful inferences than alternative procedures which pool across clusters especially when the cluster sizes are small and cluster follow‐up rates are highly variable. When pooling across clusters, the imputation procedure should generally take intracluster correlation into account to obtain valid inferences; however, as long as the intracluster correlation coefficient is small, we show that standard multiple imputation procedures may yield acceptable type I error rates; moreover, these procedures may yield more powerful inferences than a specialized procedure, especially when the number of available clusters is small. Within‐cluster multiple imputation is shown to be the least powerful among the procedures considered. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
1,3‐bis[N‐sulfonyl‐(1R,2S)‐1,3‐diphenyl‐2‐aminopropanol]benzene: An excellent ligand for titanium‐catalyzed asymmetric AlPh3(THF) additions to aldehydes
Authors: Hsieh Sheng‐Hsiang , Chen Chien‐An , Chuang Da‐Wei , Yang Mao‐Chih , Yang Hsu‐Tang , Gau Han‐Mou
Published: June 2008

Asymmetric AlPh3 (THF) additions to a wide variety of aldehydes catalyzed by a titanium catalyst of 20 mol % 1,3‐bis[N‐sulfonyl‐(1R,2S)‐1,3‐diphenyl‐2‐aminopropanol]benzene (1) are reported. The catalytic system works excellently for aromatic aldehydes bearing either an electron‐donating or an electron‐withdrawing substituent on the aromatic ring to afford secondary diaryl alcohols in excellent isolated yields of ≥95% and excellent enantioselectivities of ≥94% ee. The phenyl addition to cinnamaldehyde or 2‐furylaldehyde gave corresponding secondary alcohols in 85% and 95% ee, respectively. For aliphatic aldehydes, increasing enantioselectivities of the addition products in terms of increasing steric sizes of aldehydes are observed, and this trend goes from the linear 1‐pentanal (87% ee), the secondary cyclohexylaldehyde (95% ee) or the 2‐methylpropanal (97% ee), to the tertiary 2,2‐dimethylpropanal (99% ee). Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Parallel programming on a high‐performance application‐runtime
Authors: Goscinski Wojtek James , Abramson David
Published: June 2008

High‐performance application development remains challenging, particularly for scientists making the transition to a heterogeneous grid environment. In general areas of computing, virtual environments such as Java and .Net have proved to be successful in fostering application development, allowing users to target and compile to a single environment, rather than a range of platforms, instruction sets and libraries. However, existing runtime environments are focused on business and desktop computing and they do not support the necessary high‐performance computing (HPC) abstractions required by e‐Scientists. Our work is focused on developing an application‐runtime that can support these services natively. The result is a new approach to the development of an application‐runtime for HPC: the Motor system has been developed by integrating a high‐performance communication library directly within a virtual machine. The Motor message passing library is integrated alongside and in cooperation with other runtime libraries and services while retaining a strong message passing performance. As a result, the application developer is provided with a common environment for HPC application development. This environment supports both procedural languages, such as C, and modern object‐oriented languages, such as C#. This paper describes the unique Motor architecture, presents its implementation and demonstrates its performance and use. Copyright © 2008 John Wiley & Sons, Ltd.
Cooperative load balancing in distributed systems
Authors: Grosu D. , Chronopoulos A. T. , Leung M. Y.
Published: June 2008

A serious difficulty in concurrent programming of a distributed system is how to deal with scheduling and load balancing of such a system which may consist of heterogeneous computers. In this paper, we formulate the static load‐balancing problem in single class job distributed systems as a cooperative game among computers. The computers comprising the distributed system are modeled as M/M/1 queueing systems. It is shown that the Nash bargaining solution (NBS) provides an optimal solution (operation point) for the distributed system and it is also a fair solution. We propose a cooperative load‐balancing game and present the structure of NBS. For this game an algorithm for computing NBS is derived. We show that the fairness index is always equal to 1 using NBS, which means that the solution is fair to all jobs. Finally, the performance of our cooperative load‐balancing scheme is compared with that of other existing schemes. Copyright © 2008 John Wiley & Sons, Ltd.