bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue factor procoagulant activity of plasma microparticles is increased in patients with early-stage prostate cancer
Authors: Spath Brigitte , Friedrich Martin , Chun Felix Kyoung-Hwan , Marx Guy , Amirkhosravi Ali , Francis John , Bokemeyer Carsten , Eifrig Barbara , Haubold Katja , Rink Michael , Langer Florian 
Published: April 2009

SummaryTissue factor (TF) plays a critical role in tumour growth and metastasis, and its enhanced release into plasma in association with cellular microparticles (MPs) has recently been associated with pathological cancer progression. We have previously demonstrated significantly elevated levels of plasma TF antigen as well as systemic coagulation and platelet activation in patients with localised prostate cancer. In this prospective study, we used a highly sensitive one-stage clotting assay to measure preoperative TF-specific procoagulant activity (PCA) of plasma MPs in 68 consecutive patients with early-stage prostate cancer to further explore the relevance of circulating TF in this tumour entity. Automated calibrated thrombography was used to monitor thrombin generation in cell-free plasma samples in the absence of exogenous TF or phospholipids. Compared to healthy male controls (n=20), patients had significantly increased levels of both D-dimer and TF-specific PCA of plasma MPs (p<0.001). Furthermore, MP-associated TF PCA was higher in patients with (n=29) than in those without (n=39) laboratory evidence of an acute-phase reaction (p=0.004) and decreased to normal levels within one week after radical prostatectomy. Overall, we found a significant correlation between TF-specific PCA of plasma MPs and plasma D-dimer (p=0.002), suggesting that plasma MPs contributed to in-vivo coagulation activation in a TF-dependent manner. Thrombin generation in plasma was also significantly increased in patients compared to controls (p<0.01). Collectively, our findings suggest that TF-specific PCA of plasma MPs contributes to intravascular coagulation activation in patients with early-stage prostate cancer and may represent a potential link between hypercoagulability, inflammation, and disease progression.
Single-chain antibodies as diagnostic tools and therapeutic agents
Authors: Muhlen Constantin von zur , Elverfeldt Dominik von , Peter Karlheinz , Hagemeyer Christoph 
Published: April 2009

SummaryOver three decades after the generation of the first mouse monoclonal antibodies by Kohler and Milstein, recombinant antibodies are the fastest growing class of therapeutic proteins. Furthermore, antibodies are key detection reagents in research and diagnostics. Technology improvements have provided several approaches to manufacturing human antibodies with high affinity for biologically relevant targets. Approximately 300 development programs for therapeutic antibodies have been reported in industrial and academic laboratories, and this clearly demonstrates the expectations towards antibody technology. Antibody fragments are a subclass with growing clinical importance. This review focuses on single-chain antibodies as one of the smallest possible format for recombinant antibodies and their use as diagnostic tools and therapeutic agents. We describe the structure, selection and production of single-chain antibodies. Furthermore, we review current applications of antibody fragments focusing on thrombus targeting using fibrin- and platelet-specific single-chain antibodies as well as describing novel noninvasive imaging approaches for the diagnosis of thrombosis and inflammation.
Reflections on Power and the Post-Colonial Context: Tales from the Field
Authors: Pintchman Tracy 
Published: April 2009

AbstractThe history of ethnographic practice in anthropology is inseparable from histories of colonialism—including racist assumptions and exploitative interests. This essay comments on concerns about power and ethnographic work from a different point of view, considering the relative powerlessness of the ethnographer in the context of a relationship that developed in the field. The essay argues that power relations in the practice of ethnography are in fact quite variegated, dependent on multiple factors, and too complex and richly textured to be captured in a single, simple “first world/third world” kind of dichotomous mapping.
Hemispheric-Scale Seasonality of the Southern Annular Mode and Impacts on the Climate of New Zealand
Authors: Kidston J. , Renwick J. A. , McGregor J. 
Published: April 2009

Abstract
The seasonality of the southern annular mode (SAM) and the resulting impacts on the climate variability of New Zealand (NZ) are investigated. As with previous studies, during summer the SAM is found to be largely zonally symmetric, whereas during winter it exhibits increased zonal wavenumber 2–3 variability. This is consistent with seasonal variations in the mean state, and the authors argue that the seasonal cycle of near-surface temperature over the Australian continent plays an important role, making the eddy-driven jet, and hence the SAM, more zonally symmetric during summer than winter. During winter, the SAM exhibits little variability over the South Pacific and southeast of Australia. Dynamical reasons for this behavior are discussed.
For the NZ region this seasonality implies that fluctuations in the SAM are associated with a zonal wind speed anomaly during summer but a more meridional wind speed anomaly during winter. This behavior is well captured by temperature and rainfall station data, which serves to corroborate the seasonal changes seen in the large-scale analysis. Moreover, the mode of climate variability that corresponds to a fluctuation of the zonal wind speed is well correlated with the SAM during the summer only and exhibits less variance during the winter. This is consistent with the notion that the seasonality of the SAM significantly impacts modes of climate variability in the region.
Toward Better Understanding of the Contiguous Rain Area (CRA) Method for Spatial Forecast Verification
Authors: Ebert Elizabeth E. , Gallus William A. 
Published: April 2009

Abstract
The contiguous rain area (CRA) method for spatial forecast verification is a features-based approach that evaluates the properties of forecast rain systems, namely, their location, size, intensity, and finescale pattern. It is one of many recently developed spatial verification approaches that are being evaluated as part of a Spatial Forecast Verification Methods Intercomparison Project. To better understand the strengths and weaknesses of the CRA method, it has been tested here on a set of idealized geometric and perturbed forecasts with known errors, as well as nine precipitation forecasts from three high-resolution numerical weather prediction models.
The CRA method was able to identify the known errors for the geometric forecasts, but only after a modification was introduced to allow nonoverlapping forecast and observed features to be matched. For the perturbed cases in which a radar rain field was spatially translated and amplified to simulate forecast errors, the CRA method also reproduced the known errors except when a high-intensity threshold was used to define the CRA (≥10 mm h−1) and a large translation error was imposed (&gt;200 km). The decomposition of total error into displacement, volume, and pattern components reflected the source of the error almost all of the time when a mean squared error formulation was used, but not necessarily when a correlation-based formulation was used.
When applied to real forecasts, the CRA method gave similar results when either best-fit criteria, minimization of the mean squared error, or maximization of the correlation coefficient, was chosen for matching forecast and observed features. The diagnosed displacement error was somewhat sensitive to the choice of search distance. Of the many diagnostics produced by this method, the errors in the mean and peak rain rate between the forecast and observed features showed the best correspondence with subjective evaluations of the forecasts, while the spatial correlation coefficient (after matching) did not reflect the subjective judgments.
The Public Stigma of Mental Illness and Drug Addiction
Authors: Corrigan Patrick W. , Kuwabara Sachiko A . , O'Shaughnessy John 
Published: April 2009

• Summary: Previous research has shown that people labeled with drug addiction are viewed as more blameworthy and dangerous compared to individuals labeled with mental illness who, in turn, are viewed more harshly than those with physical disabilities. Endorsement of such stereotypes often lead to less helping behavior and more avoidance of people with drug addiction compared to those with mental illness. In this study, attribution and dangerousness models are tested on a stratified random sample of the US population. The sample was recruited from a national online research panel ( N = 815). Research participants read a vignette about a person with one of the three health conditions (mental illness, drug addiction, or physically handicapped in a wheelchair) and were asked to complete items representing attribution and dangerousness judgments about the person. • Findings: Results are consistent with our hypotheses. Addicted to drugs was seen as more blameworthy and dangerous compared to mental illness. • Applications : These findings are important for framing the stigma and stereotypes of mental illness and drug addiction are discussed. In turn, these kinds of basic models will inform stigma change efforts of advocates.
Knowing or Un-knowing? That is the Question
Authors: Blom Björn 
Published: April 2009

• Summary: A present trend in social work is the focus on evidence-based knowledge. This kind of knowledge does fill a purpose, but is not sufficient on its own. The article argues that social workers need a complement to knowing, and this approach could be conceptualized as un-knowing. In this article, a theory of un-knowing for social work practice is outlined. This implies a theoretical scrutiny of knowing and un-knowing and a discussion of how it can be used in practice. Moreover, the article presents findings from an empirical study of social work students who describe their usage of different forms of knowledge reflexively. • Findings: The article presents the results of a study in which social work students' usage of different forms of knowledge in their field studies was examined. The results demonstrate that social work students use different forms of knowledge in practice, and un-knowing is one of the actively used forms. Women tend to use un-knowing somewhat more than men. • Applications : The article is a contribution to the ongoing debate on evidence-based practice in social work. It is argued that it is important to teach social work students to understand un-knowing in theory and to use it in practice, and in combination with other forms of knowledge in social work.
The Central Role of the Therapeutic Bond in a Social Agency Setting
Authors: Knei-Paz Cigal 
Published: April 2009

• Summary: This article describes the results of a qualitative research project that was carried out in a social service agency in central Israel. The aim of the research was to identify essential elements in the creation of a positive intervention experience involving social workers and families in distress. • Findings: The main findings of the research are described and analyzed within the framework of institutional, social and political contexts, using Denzin's critical-interpretive approach. It was found that at the basis of what is conceived of as a positive intervention experienced by both families in distress and social workers alike, lies the quality of the bond that was established between these two groups. As a result of the bond, based on relations of trust and closeness, the clients experienced a significant relief from the weight of their distress and reported changes in their self-image and in their family relations. However, the work setting in the social agency — a heavy workload, extensive burdens of bureaucracy, and budgetary limitations — made it impossible for social workers to devote themselves appropriately to cultivating the bond. • Applications : The research here described also indicates that there is need for a `social dialogue' between social workers and clients in order to clarify the connection between individual family problems and the socio-political situation in Israel and to facilitate a greater role for the general public in matters concerning families in distress.
Fabled Uncertainty in Social Work
Authors: White Sue 
Published: April 2009

• Summary: In a recent issue of this journal, Marlee Spafford and her colleagues reported on a Canadian study of social work, medical and optometry students. One of their findings was that the novice social workers viewed the acknowledgement of uncertainty as a hallmark of professional competence. Drawing on data from UK-based studies of professional reasoning, this article challenges the notion that social work has embraced and engaged with uncertainty. • Findings: Despite the obvious ambiguities of many cases, much of the time social workers often feel very sure of their formulations. This is because social work takes place in the terrain of human relationships about which we all, qua human beings, routinely make moral evaluations in everyday life. Rhetoric of complexity and reflection should not be confused with uncertainty. • Applications : This article endorses Spafford et al.'s respect for uncertainty and tentativeness, but argues that it is folly to think that we already have it in social work. A tentative and sceptical vocabulary of the emotional and moral domain is required if social work is indeed to embrace and acknowledge the limits and fallibilities of its technologies and practices.
Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis
Authors: Kisucka Janka , Chauhan Anil K. , Zhao Bing-Qiao , Patten Ian S. , Yesilaltay Ayce , Krieger Monty , Wagner Denisa D. 
Published: April 2009

AbstractCerebrovascular and cardiovascular diseases are a major cause of morbidity and mortality. Soluble P-selectin (sP-selectin) is a biomarker for platelet/endothelial activation and is considered a risk factor for vascular disease. sP-selectin enhances procoagulant activity by inducing leukocyte-derived microparticle production and promotes activation of leukocyte integrins. However, it is not known whether it directly contributes to vascular complications. We investigated the effect of increased levels of sP-selectin on blood-brain barrier (BBB) function, stroke outcome, and atherosclerosis by comparing wild-type mice with P-selΔCT/ΔCT mice in which the endogenous P-selectin gene was replaced with a mutant that produces abnormally high plasma levels of sP-selectin. P-selΔCT/ΔCT mice presented several abnormalities, including (1) higher BBB permeability, with 25% of the animals showing differential permeability between the right and left hemispheres; (2) altered social behavior with increased aggression; (3) larger infarcts in the middle cerebral artery occlusion ischemic stroke model; and (4) increased susceptibility to atherosclerotic, macrophage-rich lesion development in both male and female mice on the apoE−/− genetic background. Thus, elevated sP-selectin is not only a biomarker for vascular disease, but also may contribute directly to atherosclerosis and cerebrovascular complications.
Ex vivocytokine release reflects sensitivity to occupational endotoxin exposure
Authors: Smit L. A. M. , Heederik D. , Doekes G. , Krop E. J. M. , Rijkers G. T. , Wouters I. M. 
Published: April 2009

Not everyone exposed to endotoxin develops respiratory symptoms, even at very high exposure levels. The aim was to investigate whetherex vivolipopolysaccharide (LPS)-induced cytokine release may be predictive of individual sensitivity to occupational endotoxin exposure.In 412 agricultural workers, tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 release was measured in supernatants from LPS-stimulated whole blood, lung function was measured, and respiratory symptoms were assessed by questionnaire. For each cytokine, the population was dichotomised into low and high responders according to median cytokine concentrations. Endotoxin exposure levels were determined based on 249 personal exposure measurements.High IL-10 responders had a higher prevalence of airway symptoms than low IL-10 responders (odds ratios between 2.03 and 5.10; p<0.05). TNF-α response was positively, but not significantly, associated with symptoms, whereas no relationship was found between IL-1β response and symptoms. For all three cytokines, subjects with above-median responses showed significant positive dose–response relationships between endotoxin exposure and asthma symptoms, and significant associations between endotoxin exposure and a lower forced expiratory volume in 1 s (p<0.05). In contrast, exposure–response relationships were weak and statistically nonsignificant for low responders.Theex vivoinflammatory response to LPS reflects, to a large extent, whether individuals are susceptible to adverse respiratory effects induced by high occupational endotoxin exposure.
Anti-angiogenic activity of carebastine: a plausible mechanism affecting airway remodelling
Authors: De Luisi A. , Mangialardi G. , Ria R. , Acuto G. , Ribatti D. , Vacca A. 
Published: April 2009

Ebastine is a well-known selective second-generation histamine H1receptor antagonist, which is used for seasonal and perennial allergic rhinitis and chronic urticaria. Angiogenesis plays a crucial role in the development of airway inflammation and remodelling in allergic rhinitis and asthmatic patients, in whom, indeed, the mucosa displays increased vascularity and overexpression of vascular endothelial growth factor (VEGF). The aim of the present study was to evaluate the anti-angiogenic properties of carebastine, the active metabolite of ebastine.The effects of carebastine on human umbilical vein endothelial cell (EC) (HUVEC) and human pulmonary artery EC (HPAEC) proliferation, migration and capillary-like tube formation were investigatedin vitro, and in the chick embryo chorioallantoic membrane (CAM) assayin vivo. Moreover, the effect of carebastine on phosphorylation of the cell VEGF receptor fetal liver kinase-1, or VEGF receptor 2 (VEGFR-2), and Akt kinase (Akt) was evaluated by Western blotting.Carebastine inhibited VEGF-induced HUVEC and HPAEC proliferation, migration and angiogenesis in a dose-dependent mannerin vitro. Cell proliferation was inhibited by 42 and 64% in HUVECs and 62 and 75% in HPAECs upon exposure for 48 and 72 h, respectively, to 20 μM carebastine (p≤0.03), and even more with 30 μM carebastine. Cell migration was inhibited by 37 and 70% in HUVECs (p≤0.03) and 60 and 78% in HPAECs (p≤0.01) in the presence of 10 and 30 μM carebastine, respectively. Carebastine (20 μM) caused a significant reduction (70−86%; p<0.01) in topological parameters of the capillary network producedin vitroby both EC lines on a basement membrane extract. Carebastine (30 and 50 μM) inhibited the VEGF-induced angiogenesis in the CAM assayin vivotwo- and three-fold, respectively (p<0.001). Finally, both EC lines, on exposure to 10 and 20 μM carebastine, showed a four- to six-fold reduction (p≤0.01) in both VEGF- and H1receptor-induced VEGFR-2 and Akt phosphorylation.Overall, these data provide the first evidence regarding the anti-angiogenic activity of ebastine, and suggest its potential use as an anti-angiogenic molecule, besides its antihistaminic activity for the treatment of allergic diseases in which angiogenesis takes place.
Smoking cessation interventions in COPD: a network meta-analysis of randomised trials
Authors: Strassmann R. , Bausch B. , Spaar A. , Kleijnen J. , Braendli O. , Puhan M. A. 
Published: April 2009

The aim of this study was to rank order the effectiveness of smoking cessation interventions for chronic obstructive pulmonary disease (COPD) patients.We searched 10 databases to identify randomised trials of smoking cessation counselling (SCC) with or without pharmacotherapy or nicotine replacement therapy (NRT). We conducted a network meta-analysis using logistic regression analyses to assess the comparative effectiveness of smoking cessation interventions while preserving randomisation of each trial.The analysis of 7,372 COPD patients from six out of eight identified trials showed that SCC in combination with NRT had the greatest effect on prolonged abstinence ratesversususual care (OR 5.08, p<0.0001)versusSCC alone (2.80, p = 0.001) andversusSCC combined with an antidepressant (1.53, p = 0.28). The second most effective intervention was SCC combined with an antidepressant (3.32, p = 0.002)versusSCC alone (1.83, p = 0.007), with no difference between antidepressants. SCC alone was of borderline superiority compared with usual care (1.81, p = 0.07).A small body of evidence suggests that SCC combined with NRT is more effective than other combinations and single smoking cessation treatments in COPD, but substantially more research is needed for this most important COPD treatment.
Comparative analysis indicates that alternative splicing in plants has a limited role in functional expansion of the proteome
Authors: Severing Edouard I , van Dijk Aalt DJ , Stiekema Willem J , van Ham Roeland CHJ 
Published: April 2009

Abstract

Background
Alternative splicing (AS) is a widespread phenomenon in higher eukaryotes but the extent to which it leads to functional protein isoforms and to proteome expansion at large is still a matter of debate. In contrast to animal species, for which AS has been studied extensively at the protein and functional level, protein-centered studies of AS in plant species are scarce. Here we investigate the functional impact of AS in dicot and monocot plant species using a comparative approach.

Results
Detailed comparison of AS events in alternative spliced orthologs from the dicot Arabidopsis thaliana and the monocot Oryza sativa (rice) revealed that the vast majority of AS events in both species do not result from functional conservation. Transcript isoforms that are putative targets for the nonsense-mediated decay (NMD) pathway are as likely to contain conserved AS events as isoforms that are translated into proteins. Similar results were obtained when the same comparison was performed between the two more closely related monocot species rice and Zea mays (maize).
Genome-wide computational analysis of functional protein domains encoded in alternatively and constitutively spliced genes revealed that only the RNA recognition motif (RRM) is overrepresented in alternatively spliced genes in all species analyzed. In contrast, three domain types were overrepresented in constitutively spliced genes. AS events were found to be less frequent within than outside predicted protein domains and no domain type was found to be enriched with AS introns. Analysis of AS events that result in the removal of complete protein domains revealed that only a small number of domain types is spliced-out in all species analyzed. Finally, in a substantial fraction of cases where a domain is completely removed, this domain appeared to be a unit of a tandem repeat.

Conclusion
The results from the ortholog comparisons suggest that the ability of a gene to produce more than one functional protein through AS does not persist during evolution. Cross-species comparison of the results of the protein-domain oriented analyses indicates little correspondence between the analyzed species. Based on the premise that functional genetic features are most likely to be conserved during evolution, we conclude that AS has only a limited role in functional expansion of the proteome in plants.