bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitors: our greatest challenge. Can we minimize the incidence?
Authors: Kruse‐Jarres R. 
Published: December 2012

SummaryDevelopment of alloantibodies against infused factor VIII (FVIII) is the most significant complication of haemophilia care today. Antibodies inactivate the procoagulant activity of FVIII and inhibit patients' response to replacement therapy. As inhibitors tend to develop early in the course of FVIII treatment, the challenge is to bring patients through the critical early phase of FVIII exposure without inhibitor development as the subsequent risk is much lower. Disease severity, major FVIII gene defects, family history and non‐Caucasian race are major risk factors for inhibitor development. Other variables thought to play a role in inhibitor formation include age at first treatment, intensity of early treatment, use of prophylaxis and product choice [especially recombinant vs. plasma‐derived von Willebrand factor (VWF)‐containing concentrates]. As these treatment‐related variables are modifiable, they provide opportunity to minimize inhibitor incidence at the clinical level. At present, most data regarding inhibitor development derive from retrospective studies, registry reviews, small case series and uncontrolled studies. Findings have often been conflicting, which precludes drawing definitive conclusions. Nevertheless, some clarity is beginning to emerge. Intensity of early treatment appears to be a stronger risk factor for inhibitor development than timing of first treatment. Controlled early antigen presentation via prophylaxis looks promising, particularly in conjunction with strategies to avoid immunological danger signals, but the timing of introduction and optimal regimen are not yet known. Several reports suggest that plasma‐derived VWF‐containing FVIII concentrates are less immunogenic than recombinant or VWF‐free plasma‐derived concentrates, but this is awaiting confirmation in the ongoing prospective Survey of Inhibitors in Plasma‐Product Exposed Toddlers study.
The immune tolerance induction (ITI) dose debate: does the International ITI Study provide a clearer picture?
Authors: Ettingshausen C. Escuriola , Kreuz W. 
Published: December 2012

SummaryAmong the proposed predictors for immune tolerance induction (ITI) outcome, the therapeutic regimen – specifically the dose and frequency of administered factor VIII (FVIII) as well as FVIII product type – is intensely debated. Are there any advantages for low‐dose regimens (50 IU FVIII kg−1 three times a week) over high‐dose regimens (200 IU FVIII kg day−1) or vice versa? Are von Willebrand factor (VWF)‐containing plasma‐derived concentrates superior to recombinant FVIII concentrates for tolerance induction? A review of the available literature indicates that patients with good prognostic factors can achieve success with either low‐dose or high‐dose ITI regimens. Retrospective data suggest that patient characteristics such as maximum historical inhibitor titres and pre‐ITI inhibitor titres are better predictors of treatment success than dose. Results of the prospective International ITI Study have recently become available. In inhibitor patients with good prognosis, success rates were similar between low‐dose (50 IU FVIII kg−1 three times a week) and high‐dose (200 IU FVIII kg−1 daily) regimens. However, patients receiving low‐dose ITI took longer to achieve various ITI milestones and had a significantly higher bleed rate per month compared with the high‐dose group (0.62 vs. 0.28; P = 0.00024), findings with important clinical implications. Inhibitor patients with poor prognostic features should be treated with a high‐dose protocol. This conclusion is supported by a meta‐analysis of the International Immune Tolerance Registry and North American Immune Tolerance Registry and by data from Germany showing good success rates with the high‐dose, high‐frequency Bonn protocol in poor prognosis patients. Type of concentrate also appears to have an influence on ITI success rates in this patient subgroup, with evidence suggesting an advantage for VWF‐containing plasma‐derived FVIII concentrates over recombinant or VWF‐free concentrates. The ongoing prospective studies REScue Immunotolerance STudy and Observational Immune Tolerance Induction are evaluating ITI outcome with respect to product type and are expected to answer this important clinical question as well as provide greater insight into patient‐ and therapy‐related variables in inhibitor patients with poor prognostic features.
An α‐l‐rhamnosidase from Aspergillus awamori MTCC‐2879 and its role in debittering of orange juice
Authors: Yadav Sarita , Yadav Rama S. S. , Yadav Kapil D. S. 
Published: December 2012

SummaryThe extracellular α‐l‐rhamnosidase has been purified by growing a new fungal strain Aspergillus awamori MTCC‐2879 in the liquid culture growth medium containing orange peel. The purification procedure involved ultrafiltration using PM‐10 membrane and anion‐exchange chromatography on diethyl amino ethyl cellulose. The purified enzyme gave single protein band in SDS‐PAGE analysis corresponding to molecular mass 75.0 kDa. The native PAGE analysis of the purified enzyme also gave a single protein band, confirming the purity of the enzyme. The Km and Vmax values of the enzyme for p‐nitrophenyl‐α‐l‐rhamnopyranoside were 0.62 mm and 27.06 μmole min−1 mg−1, respectively, yielding kcat and kcat/km values 39.90 s−1 and 54.70 mm−1 s−1, respectively. The enzyme had an optimum pH of 7.0 and optimum temperature of 60 °C. The activation energy for the thermal denaturation of the enzyme was 35.65 kJ−1 mol−1 K−1. The purified enzyme can be used for specifically cleaving terminal α‐l‐rhamnose from the natural glycosides, thereby contributing to the preparation of pharmaceutically important compounds like prunin and l‐rhamnose.
Can tamsulosin facilitate expulsion of ureteral stones? A meta‐analysis of randomized controlled trials
Authors: Fan Bo , Yang Deyong , Wang Jianbo , Che Xiangyu , Li Xiancheng , Wang Lina , Chen Feng , Wang Tiezheng , Song Xishuang 
Published: December 2012

ObjectivesTo determine the efficacy and safety of the adrenergic alpha‐antagonist tamsulosin in facilitating ureteral stones expulsion.MethodsA literature search was carried out using the PubMed database, Medline via Ovid, Embase and the Cochrane Library database to identify randomized controlled trials evaluating the efficiency of tamsulosin in the treatment of ureteral stones. Meta‐analysis and forest plots were carried out by use of Review Manager version 5.1 software (Cochrane Collaboration).ResultsCompared with the control group, the tamsulosin group had an increase in expulsion rate of 51% and a decrease in expulsion time of 2.63 days. Furthermore, tamsulosin was found to reduce the risk of ureteral colic during treatment by 40% and also the risk of requirement of auxiliary procedures during follow up by 60%. In terms of safety, the tamsulosin group had a 117% increase in the incidence of side‐effects compared with the control group, especially for incidence of dizziness.ConclusionTamsulosin facilitates the expulsion of ureteral calculi by providing a higher expulsion rate, a shorter expulsion time, a lower incidence of ureteral colic during treatment and a lower requirement of auxiliary procedures. However, the incidence of dizziness occurring during tamsulosin treatment is significantly higher in this setting.
Super‐resolution characterization of TCR‐dependent signaling clusters
Authors: Sherman Eilon , Barr Valarie , Samelson Lawrence E. 
Published: December 2012

SummaryMulti‐molecular signaling complexes drive the earliest events of immune cell activation via immunoreceptors with unexplained specificity and speed. Fluorescence microscopy has shown that these complexes form microclusters at the plasma membrane of activated T cells upon engagement of their antigen receptors (TCRs). Although crucial for cell function, much remains to be learned about the molecular content, fine structure, formation mechanisms, and function of these microclusters. Recent advancements in super‐resolution microscopy have enabled the study of signaling microclusters at the single molecule level with resolution down to approximately 20 nm. These techniques have now helped to characterize the size distributions of signaling clusters at the plasma membrane of intact cells and to shed light on the formation mechanisms that govern their assembly. Surprisingly, dynamic and functional nanostructures have been identified within the signaling clusters. We expect that these novel methodologies, combined with older techniques, will shed new light on the nature of signaling clusters and their critical role in T‐cell activation.
The function of sub‐synaptic vesicles during T‐cell activation
Authors: Purbhoo Marco A. 
Published: December 2012

SummaryThe immune synapse is central to the regulation of T‐cell activation and effector functions. Vesicular compartments dynamically interact with the immune synapse. Here they take part in the trafficking of signaling components to and from the synaptic cleft, as well as in the directed delivery and release of T‐cell effector compounds. In addition to ferrying cargo, emerging evidence indicates that vesicular compartments at the immune synapse are actively involved in the signaling processes which underlie T‐cell activation, specifically that they productively interact with signaling microclusters at the synapse, or become sites of signaling themselves. How different classes of sub‐synaptic vesicular compartments associate with the immune synapse and to what extent they influence the processes there remains only partially understood. I here discuss the mechanisms underlying the interactions between vesicular compartments and the immune synapse and the contributions such interactions have on T‐cell activity, with particular focus on the advantages to the regulation of T‐cell signaling.
Building tolerance by dismantling synapses: inhibitory receptor signaling in natural killer cells
Authors: Huse Morgan , Catherine Milanoski S. , Abeyweera Thushara P. 
Published: December 2012

SummaryCell surface receptors bearing immunotyrosine‐based inhibitory motifs (ITIMs) maintain natural killer (NK) cell tolerance to normal host tissues. These receptors are difficult to analyze mechanistically because they block activating responses in a rapid and comprehensive manner. The advent of high‐resolution single cell imaging techniques has enabled investigators to explore the cell biological basis of the inhibitory response. Recent studies using these approaches indicate that ITIM‐containing receptors function at least in part by structurally undermining the immunological synapse between the NK cell and its target. In this review, we discuss these new advances and how they might relate to what is known about the biochemistry of inhibitory signaling in NK cells and other cell types.
Cellular immune reactions in the lung
Authors: Hasenberg Mike , Stegemann‐Koniszewski Sabine , Gunzer Matthias 
Published: December 2012

SummaryThe lung constantly interacts with the environment through thousands of liters of air that are inhaled daily. This continually transports toxic chemicals and particles or pathogenic microorganisms deep into the respiratory system, posing a challenge to physicochemical barriers and the local immune system. Thus, complex structures and mechanisms have evolved to recognize and fend off environmental dangers while at the same time allowing efficient gas exchange. Here we review our current knowledge regarding cellular mechanisms of the immune system in context with the highly specialized anatomical features of the airways and especially the alveolar compartment. The focus is on fungal and viral infections, merging anatomical aspects well known to pulmonologists with fundamental immunological concepts. We discuss the specialized morphological constraints of immune cells compressed under a continuous layer of the surfactant lining within alveoli as well as the importance of functional polarization of respiratory tract epithelia. Furthermore, we summarize the different types of innate and adaptive immune cells and their relative contribution to lung homeostasis with respect to localization. Finally, we provide a list of currently unresolved questions with high relevance for the field that might serve as food for thought regarding future research directions.
Workers' Views of the Impact of Trade on Jobs
Authors: Brown Clair , Lane Julia , Sturgeon Timothy 
Published: December 2012

This article uses new data to examine how workers' perceptions of the impact of trade on jobs like theirs are related to economic variables representing their career paths, job characteristics, and local labor market conditions. We find that only 17 percent of workers think trade creates jobs. And even fewer workers (4–7 percent) in any industry think trade has created better jobs. We find that workers' perceptions do not reflect their job characteristics or the movability of their jobs. Their perceptions of trade primarily reflect local labor market conditions (hiring and separation rates) and education. The determinants of workers' perceptions of trade present a different pattern compared with their perceptions of job security.
The coordinate regulation of sensory afferent CNS targeting and CNS longitudinal tract organization in Drosophila during neural development
Authors: Wu Zhuhao , Andreone Benjamin J. , Kolodkin Alex L. 
Published: December 2012

AbstractLongitudinal axon fascicles within the Drosophila embryonic CNS provide connections between body segments and are required for coordinated neural signaling along the anterior‐posterior axis. We find that the establishment of CNS longitudinal tracts, and the formation of precise chordotonal mechanosensory afferent innervation to the same CNS region, are coordinately regulated by the secreted semaphorins Sema‐2a and Sema‐2b. Both Sema‐2a and Sema‐2b utilize the same neuronal receptor, plexin B (PlexB), but they serve repulsive and attractive functions, respectively, to promote interneuron fascicle assembly and sensory afferent connectivity. In the absence of Sema‐2b or PlexB, chordotonal afferent connectivity within the CNS is severely disrupted, as are select interneuron pathways within longitudinal fascicles, resulting in specific larval behavioral deficits. These results reveal that distinct semaphorin‐mediated guidance functions converge at the PlexB receptor, and that attractive and repulsive functions mediated by this receptor are critical for functional neural circuit assembly.
Recent developments and future directions in Guillain‐Barré syndrome
Authors: Lehmann Helmar C. , Hughes Richard A. C. , Kieseier Bernd C. , Hartung Hans‐Peter 
Published: December 2012

AbstractGuillain‐Barré syndrome (GBS) encompasses a spectrum of acquired neuropathic conditions characterized by inflammatory demyelinating or axonal peripheral neuropathy with acute onset. Clinical and experimental studies in the past years have led to substantial progress in epidemiology, pathogenesis of GBS variants, and identification of prognostic factors relevant to treatment. In this review we provide an overview and critical assessment of the most recent developments and future directions in GBS research.
Competition and Sustainability: The Impact of Consumer Awareness
Authors: Galbreth Michael R. , Ghosh Bikram 
Published: December 2012

ABSTRACTSustainability, a broad concept that includes numerous environmental and social dimensions, has emerged as an important product evaluation criterion for consumers. We suggest the impact of sustainability on consumer behavior depends on two factors—each individual consumer's unique level of concern about sustainability, and the general level of awareness regarding the sustainability of competing products—that together determine the level of heterogeneity among consumer attitudes toward sustainability. We incorporate sustainability concern and awareness into a model of horizontal competition in a duopoly, where one firm's product is more sustainable than the other's. Our results suggest that marginal increases in awareness can benefit all firms, including the less sustainable one, when awareness is sufficiently high (the explicit goal of recent sustainability labeling initiatives). In several model extensions, we provide additional insights for the following cases: the sustainable firm controls the extent of its sustainability advantage, the sustainable firm can directly influence the general level of awareness, and the distribution of sustainability concern across consumers is nonuniform. Our results enable us to suggest several new insights for managers, both those whose products enjoy a sustainability advantage and those whose products do not.
HER2/neu expression correlates with vasculogenic mimicry in invasive breast carcinoma
Authors: Liu Tieju , Sun Baocun , Zhao Xiulan , Gu Qiang , Dong Xueyi , Yao Zhi , Zhao Nan , Chi Jiadong , Liu Ning , Sun Ran , Ma Yuemei 
Published: December 2012

AbstractVasculogenic mimicry (VM) refers to the condition in which tumour cells mimic endothelial cells to form extracellular matrix‐rich tubular channels. VM is more extensive in more aggressive tumours. The human epidermal growth factor receptor 2 (HER2) gene is amplified in 20–30% of human breast cancers and has been implicated in mediating aggressive tumour growth and metastasis. However, thus far, there have been no data on the role of HER2 in VM formation. Immunohistochemical and histochemical double‐staining methods were performed to display VM in breast cancer specimens. Transfection in MCF7 cells was performed and clones were selected by G418. The three‐dimensional Matrigel culture was used to evaluate VM formation in the breast cancer cell line. According to statistical analysis, VM was related to the presence of a positive nodal status and advanced clinical stage. The positive rate of VM increased with increased HER2 expression. In addition, cases with HER2 3+ expression showed significantly greater VM channel count than those in other cases. The exogenous HER2 overexpression in MCF‐7 cells induced vessel‐like VM structures on the Matrigel and increased the VM mediator vascular endothelial (VE) cadherin. Our data provide evidence for a clinically relevant association between HER2 and VM in human invasive breast cancer. HER2 overexpression possibly induces VM through the up‐regulation of VE cadherin. Understanding the key molecular events may provide therapeutic intervention strategies for HER2+ breast cancer.
Perspectives on the use of and service needs of cancer preventive services for ethnic minorities in Hong Kong: a study protocol
Authors: So Winnie K.W. , Chan Carmen W.H. , Choi Kai‐chow , Chan Dorothy N.S. 
Published: December 2012

AbstractAimTo report a study protocol to explore the experience of cancer screening from the perspective of ethnic minorities in Hong KongBackgroundCancer is a major health problem, but screening can be effective in decreasing the incidence and mortality rates. Providing information on how to participate in recommended preventive measures and on accessibility to these services is a crucial step in promoting healthy behaviour. Ethnic minorities in Western countries are found to be less likely to use preventive services and encounter more barriers in doing so than the general population.DesignA mixed‐method design with two phases has been chosen to meet the aims and objectives of the study, with Phase 1 using a self‐reported survey and Phase 2 involving focus‐group interviews.MethodA convenience sample of 1540 South Asians (770 in each gender) will be recruited from community centres for the Phase 1 survey in 2013–2014, of whom 72–96 will be invited to participate in the Phase 2 interviews. The Survey and Behavioural Research Ethics Committee of the local university approved the study in March 2012.DiscussionThe findings will provide detailed information on the use of cancer screening and the barriers that this minority population faces in Hong Kong. The findings will inform the government and policy‐makers on the implementation of culture‐specific interventions, so as to increase the screening uptake rate of this ethnic minority.
Genetic parameters for birthweight environmental variability in mice
Authors: Pun A. , Cervantes I. , Nieto B. , Salgado C. , Pérez‐Cabal M.A. , Ibáñez‐Escriche N. , Gutiérrez J.P. 
Published: December 2012

SummaryData from a divergent experiment for birthweight (BrW) environmental variability were used to estimate genetic parameters forBrWtrait and its environmental variability by fitting both homoscedastic (HO) and heteroscedastic (HE) models. A total of 5 475 records ofBrWfrom animals born from inbred dams, and 7 140 pedigree records were used. The heritability ofBrWusing the modelHOwas 0.27, with the litter effect much more important, 0.43. The modelHEprovided a genetic correlation between the trait and its environmental variability that was very high and negative, −0.97, and a high value for the additive genetic variance for environmental variability, suggesting an artefact in the model. The residual skewness was found to be essentially null. A model considering the genetic correlation null was also fitted, and used to obtain the breeding values for the selection process. Moreover, the trait was considered as maternal resulting in similar estimates under the modelHO, but more reasonable for the genetic correlation between the trait and its environmental variability of 0.48 with a value of 0.25 for the additive genetic variance regarding environmental variability under the modelHE. This led to the conclusion that environmental variability ofBrWin mice must be selected via dams. Estimated parameters in a reduced dataset without inbred animals did not substantially change this conclusion.
Pharmacokinetic analysis of oral doxycycline in rhesus macaques
Authors: Embers Monica E. , Hasenkampf Nicole R. , Embers Dale G. , Doyle Lara A. 
Published: December 2012

AbstractBackgroundFollowing administration of an antibiotic, the concentration in blood changes over time and is dependent on the type of antibiotic, the route and species of the individual. The most relevant pharmacodynamic property of a bacteriostatic antibiotic such as doxycycline is the minimum inhibitory concentration (MIC), whereas pharmacokinetics may include rates of absorption and elimination from blood.MethodsWe determined serum concentrations of doxycycline following administration of 5 mg/kg in two macaques.ResultsThe area under the concentration–time curve over 24 hours (AUC0–24) following two doses was extrapolated from the curve over 12 hours following a single dose, with the purpose of calculating the AUC0–24:MIC.ConclusionsOther than a somewhat faster rate of elimination, the PK‐PD values for doxycycline in macaques appears similar to those determined for humans. This information will be valuable for treating disease in macaques and for research in bacterial infection models that use macaques.