bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity-based protein profiling of the hepatitis C virus replication in Huh-7 hepatoma cells using a non-directed active site probe
Authors: Singaravelu Ragunath , Blais David R , McKay Craig S , Pezacki John Paul 
Published: February 2010

Abstract

Background
Hepatitis C virus (HCV) poses a growing threat to global health as it often leads to serious liver diseases and is one of the primary causes for liver transplantation. Currently, no vaccines are available to prevent HCV infection and clinical treatments have limited success. Since HCV has a small proteome, it relies on many host cell proteins to complete its life cycle. In this study, we used a non-directed phenyl sulfonate ester probe (PS4≡) to selectively target a broad range of enzyme families that show differential activity during HCV replication in Huh-7 cells.

Results
The PS4≡ probe successfully targeted 19 active proteins in nine distinct protein families, some that were predominantly labeled in situ compared to the in vitro labeled cell homogenate. Nine proteins revealed altered activity levels during HCV replication. Some candidates identified, such as heat shock 70 kDa protein 8 (or HSP70 cognate), have been shown to influence viral release and abundance of cellular lipid droplets. Other differentially active PS4≡ targets, such as electron transfer flavoprotein alpha, protein disulfide isomerase A5, and nuclear distribution gene C homolog, constitute novel proteins that potentially mediate HCV propagation.

Conclusions
These findings demonstrate the practicality and versatility of non-directed activity-based protein profiling (ABPP) to complement directed methods and accelerate the discovery of altered protein activities associated with pathological states such as HCV replication. Collectively, these results highlight the ability of in situ ABPP approaches to facilitate the identification of enzymes that are either predominantly or exclusively labeled in living cells. Several of these differentially active enzymes represent possible HCV-host interactions that could be targeted for diagnostic or therapeutic purposes.
Performance of circulating cathodic antigen (CCA) urine-dipsticks for rapid detection of intestinal schistosomiasis in schoolchildren from shoreline communities of Lake Victoria
Authors: Standley CJ , Lwambo NJS , Lange CN , Kariuki HC , Adriko M , Stothard JR 
Published: February 2010

Abstract
For disease surveillance and mapping within large-scale control programmes, RDTs are becoming popular. For intestinal schistosomiasis, a commercially available urine-dipstick which detects schistosome circulating cathodic antigen (CCA) in host urine is being increasingly applied, however, further validation is needed. In this study, we compared the CCA urine-dipstick test against double thick Kato-Katz faecal smears from 171 schoolchildren examined along the Tanzanian and Kenyan shorelines of Lake Victoria. Diagnostic methods were in broad agreement; the mean prevalence of intestinal schistosomiasis inferred by Kato-Katz examination was 68.6% (95% confidence intervals (CIs) = 60.7-75.7%) and 71.3% (95% CIs = 63.9-78.8%) by CCA urine-dipsticks. There were, however, difficulties in precisely 'calling' the CCA test result, particularly in discrimination of 'trace' reactions as either putative infection positive or putative infection negative, which has important bearing upon estimation of mean infection prevalence; considering 'trace' as infection positive mean prevalence was 94.2% (95% CIs = 89.5-97.2%). A positive association between increasing intensity of the CCA urine-dipstick test band and faecal egg count was observed. Assigning trace reactions as putative infection negative, overall diagnostic sensitivity (SS) of the CCA urine-dipstick was 87.7% (95% CIs = 80.6-93.0%), specificity (SP) was 68.1% (95% CIs = 54.3-80.0%), positive predictive value (PPV) was 86.1% (95% CIs = 78.8-91.7%) and negative predictive value (NPV) was 71.1% (95% CIs = 57.2-82.8%). To assist in objective defining of the CCA urine-dipstick result, we propose the use of a simple colour chart and conclude that the CCA urine-dipstick is a satisfactory alternative, or supplement, to Kato-Katz examination for rapid detection of intestinal schistosomiasis.
Identification of complex metabolic states in critically injured patients using bioinformatic cluster analysis
Authors: Cohen Mitchell J , Grossman Adam D , Morabito Diane , Knudson M Margaret , Butte Atul J , Manley Geoffrey T 
Published: February 2010

Abstract
Introduction
Advances in technology have made extensive monitoring of patient physiology the standard of care in intensive care units (ICUs). While many systems exist to compile these data, there has been no systematic multivariate analysis and categorization across patient physiological data. The sheer volume and complexity of these data make pattern recognition or identification of patient state difficult. Hierarchical cluster analysis allows visualization of high dimensional data and enables pattern recognition and identification of physiologic patient states. We hypothesized that processing of multivariate data using hierarchical clustering techniques would allow identification of otherwise hidden patient physiologic patterns that would be predictive of outcome.

Methods
Multivariate physiologic and ventilator data were collected continuously using a multimodal bioinformatics system in the surgical ICU at San Francisco General Hospital. These data were incorporated with non-continuous data and stored on a server in the ICU. A hierarchical clustering algorithm grouped each minute of data into 1 of 10 clusters. Clusters were correlated with outcome measures including incidence of infection, multiple organ failure (MOF), and mortality.

Results
We identified 10 clusters, which we defined as distinct patient states. While patients transitioned between states, they spent significant amounts of time in each. Clusters were enriched for our outcome measures: 2 of the 10 states were enriched for infection, 6 of 10 were enriched for MOF, and 3 of 10 were enriched for death. Further analysis of correlations between pairs of variables within each cluster reveals significant differences in physiology between clusters.

Conclusions
Here we show for the first time the feasibility of clustering physiological measurements to identify clinically relevant patient states after trauma. These results demonstrate that hierarchical clustering techniques can be useful for visualizing complex multivariate data and may provide new insights for the care of critically injured patients.
Patients' Benefit-Risk Preferences for Chronic Idiopathic Thrombocytopenic Purpura Therapies
Authors: Hauber A Brett , Johnson F Reed , Grotzinger Kelly M , Özdemir Semra 
Published: February 2010

Background: Idiopathic thrombocytopenic purpura (ITP) primarily is a disorder of adults characterized by autoantibody-induced platelet destruction and reduced platelet production, leading to a low peripheral blood platelet count. The long-term management of many patients with chronic ITP is unsatisfactory, largely due to the variable efficacy and risks of severe adverse effects associated with current treatment options. Objective: To estimate patients' benefit-risk preferences for treatments for ITP. Methods: Patients' adverse event risk tolerance and the levels of benefit required to offset possible risks were evaluated using choice-format conjoint analysis. Subjects chose between pairs of hypothetical treatment alternatives defined by probability of achieving safe platelet levels, need for corticosteroids, mode of administration, risk of rebound, risk of elevated liver enzyme levels, and risk of thromboembolism. Results: In this study, we demonstrate that patients have clear and measurable benefit-risk preferences that physicians should consider when discussing treatment options with their patients. Patients were willing to accept significant risks of adverse events in return for an increase in the probability of achieving safe platelet levels, to avoid corticosteroids, and for more convenient administration. Patients were willing to accept significant risks of rebound and elevated liver enzymes for improvements in outcomes. Conclusions: These results demonstrate that patients with ITP are willing to accept treatment-related risks in exchange for improvements in treatment efficacy and administration attributes and suggest the importance of considering a patient's benefit-risk preferences during discussions of therapeutic options.
Takotsubo Cardiomyopathy, or Broken-Heart Syndrome
Authors: Nykamp Diane , Titak John Adam 
Published: February 2010

Objective: To report a case of takotsubo cardiomyopathy, also known as apical ballooning syndrome or stress cardiomyopathy. Case Summary: A 68-year-old female with a history of hypertension, hyperlipidemia, and anxiety presented with symptoms that mimicked acute coronary syndrome (ACS); the chief symptom was chest tightness. An electrocardiogram showed normal sinus rhythm, with minimal ST elevation in the anterior leads. The patient was initially treated for ST-segment elevation myocardial infarction and symptoms resolved. Coronary angiography ruled out ACS and confirmed a diagnosis of takotsubo cardiomyopathy. Discussion: Takotsubo cardiomyopathy is commonly triggered by severe emotional or psychological stress and occurs primarily in postmenopausal women. A reversible contractility abnormality of the left ventricle causes the ventricle to take on a balloon-like appearance; hence the name of tako-tsubo, a Japanese octopus fishing pot that has a narrow neck and a wide midsection. Signs and symptoms of takotsubo cardiomyopathy mimic those of ACS. Takotsubo cardiomyopathy is best diagnosed with coronary angiography, which can rule out blockage. Treatment usually consists of carvedilol and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocking agent it left ventricular ejection fraction is less than 40%. The syndrome is usually spontaneously reversible and cardiovascular function returns to normal after a few weeks. Conclusions: Takotsubo cardiomyopathy causes a reversible left ventricle dysfunction which occurs most commonly in postmenopausal women with or without cardiovascular disease. Recognition is detected with coronary angiography. It is thought to primarily be due to an abnormally high sympathetic stimulation after emotional or psychological stress. Treatment consists of an angiotensin-converting enzyme inhibitor and/or beta blocker if needed for left ventricular dysfunction and possibly an anxiolytic agent.
Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation
Authors: Ohler Anke , Debela Mekdes , Wagner Susanne , Magdolen Viktor , Becker-Pauly Christoph 
Published: February 2010

Abstract
The metalloproteases meprin α and β are expressed in several tissues, leukocytes, and cancer cells. In skin, meprins are located in separate layers of human epidermis indicating distinct physiological functions, supported by effects on cultured keratinocytes. Meprin β induces a dramatic change in cell morphology and a significant reduction in cell number, whereas in vitro evidence suggests a role for meprin α in basal keratinocyte proliferation. Meprins are secreted as zymogens that are activated by tryptic proteolytical processing. Here, we identify human kallikrein-related peptidases (KLKs) 4, 5, and 8 to be specific activators of meprins. KLK5 is capable of activating both metalloproteases. Interestingly, KLK4 and 8 cleave off the propeptide of meprin β only, whereas in contrast plasmin exclusively transforms meprin α to its mature form. Moreover, we show that proKLK7 is processed by meprins. N-terminal sequencing revealed cleavage by meprin β two amino acids N-terminal to mature KLK7. Interestingly, this triggering led to an accelerated activation of the serine protease in the presence of trypsin, but not of other tryptic KLKs, such as KLK2, 4, 5, 8, or 11. In summary, we demonstrate a specific interaction between meprin metalloproteases and kallikrein-related peptidases, revealing possible interactions within the proteolytic web.
Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation
Authors: Malcikova Jitka , Tichy Boris , Damborsky Jiri , Kabathova Jitka , Trbusek Martin , Mayer Jiri , Pospisilova Sarka 
Published: February 2010

Abstract
Sequence-specific DNA binding is the key function through which tumor suppressor p53 exerts transactivation of the downstream target genes, often being impaired in cancer cells by mutations in the TP53 gene. Functional protein microarray technology enables a high-throughput parallel analysis of protein properties within one experiment under the same conditions. Using an array approach, we analyzed the DNA binding activity of wild type p53 protein and of 49 variants. Our results show significant differences in the binding properties between the p53 mutants. The C-terminal mutant R337C displayed the highest DNA binding activity on the array. However, the same mutant showed only a partial activation in the reporter gene assay and almost no activation of downstream target genes after transfection of expression vector into cells lacking endogenous p53. These observations demonstrate that DNA binding itself is not sufficient for activating the p53 target genes in at least some of the p53 mutants and, therefore, in vitro studies might not always reflect in vivo conditions.
Entwurf sättigender Regler für polynomiale Systeme mit StellgrößenbeschränkungDesign of Saturating Controllers for Polynomial Systems with Input Constraints
Authors: Gußner Thomas , Lens Hendrik , Adamy Jürgen 
Published: February 2010

Zusammenfassung
In diesem Artikel wird eine Reglerentwurfsmethode für polynomiale Systeme mit Stellgrößenbeschränkungen vorgestellt, die auf der Sum-of-squares-Zerlegung von Polynomen basiert. Die betrachteten Regelgesetze bestehen aus einer Komposition der Sättigungsfunktion und einer polynomialen bzw. gebrochen rationalen Funktion. Neben dem Regelgesetz errechnet die Methode eine Abschätzung des Einzugsgebiets. Es werden zwei mögliche Entwurfsziele betrachtet: Die Konvergenzrate und die Größe des Einzugsgebiets. Das dem Entwurf zu Grunde liegende Optimierungsproblem ist multilinear in den Parametern und daher nicht konvex. Deshalb wird ein Algorithmus zur lokalen Optimierung solcher nichtkonvexen Probleme vorgeschlagen, der zur Lösung des zuvor aufgestellten Entwurfsproblems verwendet wird. Anhand eines Beispielsystems werden die Ergebnisse illustriert.
Ein präziser Impedanzanalysator für resonante SensorenA Precise Impedance Analyser for Resonating Sensors
Authors: Niedermayer Alexander O. , Reichel Erwin K. , Jakoby Bernhard 
Published: February 2010

Zusammenfassung
Präzise Impedanzanalysatoren werden in jüngerer Vergangenheit vermehrt zur Auswertung resonanter Sensoren eingesetzt. In diesem Beitrag wird dazu ein Schaltungskonzept vorgestellt und der geplante Einsatz, ein Viskositätssensor basierend auf einem Quarz-Schwinger zur Überwachung eines Zeolith-Kristallisationsexperimentes auf der Internationalen Raumstation (ISS), präsentiert.
Massendurchflusssensor für pneumatisch geförderte, pulverisierte Feststoffe in Förderleitungen, basierend auf linkshändigen LeitungsstrukturenLeft-handed Transmission Line Mass Flow Meter for Particulate Solids in Pipelines
Authors: Penirschke Andreas , Puentes Margarita , Schüßler Martin , Jakoby Rolf 
Published: February 2010

Zusammenfassung
Ein Massendurchflusssensor zur Bestimmung von geförderten Stäuben mit Hilfe von resonanten “Composite Right-/Lefthanded”-Leitungsstrukturen (CRLH) wurde entwickelt. Das vorgestellte Sensorprinzip bietet die Möglichkeit, kostengünstige Massendurchflusssensoren für pneumatisch geförderte Feststoffe mit hoher Messgüte zu realisieren. Die Nutzung der Raumfiltermethode zur Geschwindigkeitsmessung eröffnet zudem die Möglichkeit, mit dem CRLH-Sensor die Materialkonzentration und -geschwindigkeit des Fördergutes mit einer einzigen Messung zu bestimmen. Mögliche Anwendungsgebiete dieser Art von Sensoren ist die Bestimmung des Massendurchflusses von Luft/Feststoff-, Luft/Flüssigkeit- und Flüssigkeit/Feststoff-Mischungen in der Prozessüberwachung.
The impact of the CAG repeat polymorphism of the androgen receptor gene on muscle and adipose tissues in 20–29-year-old Danish men: Odense Androgen Study
Authors: Nielsen Torben Leo , Hagen Claus , Wraae Kristian , Bathum Lise , Larsen Rasmus , Brixen Kim , Andersen Marianne 
Published: February 2010

BackgroundThe number of CAG repeats (CAGn) within the CAG repeat polymorphism of the androgen receptor gene correlates inversely with the transactivation of the receptor.ObjectiveTo examine the impact of CAGnon muscle, fat distribution, and circulating androgen levels.Design, settings and participantsPopulation-based, cross-sectional study of 783 Danish men aged 20–29 years.MethodsGenotyping was performed in 767 men. Areas of thigh and lower trunk muscle (musclethighand musclelower trunk), subcutaneous adipose tissues (SATthighand SATlower trunk), and deep adipose tissues (i.m. and visceral) were measured in 393 men by magnetic resonance imaging (MRI). Lean body mass (LBM) and fat mass (FM) were measured in all men by whole body dual-energy X-ray absorptiometry (DEXA). The absolute areas acquired by MRI were the main outcomes. The absolute DEXA measurements and relative assessments of both modalities were considered as the secondary outcomes.ResultsCAGn(range: 10–32) correlated inversely with absolute musclethigh(r=−0.108), absolute musclelower trunk(r=−0.132), relative musclethigh(r=−0.128), relative musclelower trunk(r=−0.126), relative LBMlower extremity(r=−0.108), and relative LBMtotal(r=−0.082), and positively with relative SATthigh(r=0.137), relative SATlower trunk(r=0.188), relative FMlower extremity(r=0.107), and relative FMtotal(r=0.082). These relationships remained significant, controlling for physical activity, smoking, chronic disease, and age. CAGndid not correlate with any circulating androgen.ConclusionsThe CAG repeat polymorphism affects body composition in young men: absolute musclethighand absolute musclelower trunkincrease as CAGndecreases. Expressed relatively, muscle areas and LBM increase, while SAT and FM decrease as CAGndecreases. The polymorphism does not affect deep adipose tissues or circulating androgen levels in young men.
Educating today's democratic citizen
Authors: Bernstein Jeffrey L. 
Published: February 2010

What are we in higher education to make of the recent calls for citizenship education to play a larger role in the academy? As Matt Hartley’s paper in this issue of Learning and Teaching suggests, colleges and universities in the United States have been paying increased attention to educating for citizenship in recent decades; Bob Simpson’s concluding commentary makes similar arguments about increased expectations forcitizenship education in Europe. As our institutions of higher learning confront economic pressures, increased competition (including from for-profit entities) and calls for accountability through meaningful assessments of student learning, they will also face increased pressure to graduate not just educated individuals, but also individuals who are connected, as citizens, to the local, national and transnational world in which they live.
Microvascular decompression after failed Gamma Knife surgery for trigeminal neuralgia: a safe and effective rescue therapy?
Authors: Sekula Raymond F. , Frederickson Andrew M. , Jannetta Peter J. , Bhatia Sanjay , Quigley Matthew R. 
Published: February 2010

Object
Stereotactic radiosurgical rhizolysis using Gamma Knife surgery (GKS) is an increasingly popular treatment for medically refractory trigeminal neuralgia. Because of the increasing use of GKS for trigeminal neuralgia, clinicians are faced with the problem of choosing a subsequent treatment plan if GKS fails. This study was conducted to identify whether microvascular decompression (MVD) is a safe and effective treatment for patients who experience trigeminal neuralgia symptoms after GKS.

Methods
From their records, the authors identified 29 consecutive patients who, over a 2-year period, underwent MVD following failed GKS. During MVD, data regarding thickened arachnoid, adhesions between vessels and the trigeminal nerve, and trigeminal nerve atrophy/discoloration were noted. Outcome and complication data were also recorded.

Results
The MVD procedure was completed in 28 patients (97%). Trigeminal nerve atrophy was noted in 14 patients (48%). A thickened arachnoid was noted in 1 patient (3%). Adhesions between vessels and the trigeminal nerve were noted in 6 patients (21%) and prevented MVD in 1 patient. At last follow-up, 15 patients (54%) reported an excellent outcome after MVD, 1 (4%) reported a good outcome, 2 (7%) reported a fair outcome, and 10 patients (36%) reported a poor outcome. After MVD, new or worsened facial numbness occurred in 6 patients (21%). Additionally, 3 patients (11%) developed new or worsened troubling dysesthesias.

Conclusions
Thickened arachnoid, adhesions between vessels and the trigeminal nerve, and trigeminal nerve atrophy/discoloration due to GKS did not prevent completion of MVD. An MVD is an appropriate and safe “rescue” therapy following GKS, although the risks of numbness and troubling dysesthesias appear to be higher than with MVD alone.
Alteration of thrombospondin-1 and -2 in rat brains following experimental intracerebral hemorrhage
Authors: Zhou Hua-Jun , Zhang Hai-Nan , Tang Tao , Zhong Jian-Hua , Qi Yong , Luo Jie-Kun , Lin Yuan , Yang Qi-Dong , Li Xing-Qun 
Published: February 2010

Object
Spontaneous intracerebral hemorrhage (ICH) is among the most intractable forms of stroke. Angiogenesis, an orchestrated balance between proangiogenic and antiangiogenic factors, is a fundamental process to brain development and repair by new blood vessel formation from preexisting ones and can be induced by ICH. Thrombospondin (TSP)–1 and TSP-2 are naturally occurring antiangiogenic factors. The aim of this study was to observe their expression in rat brains with ICH.

Methods
Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by stereotactic injection of collagenase VII or autologous blood into the right globus pallidus. The expression of TSP-1 and -2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription–polymerase chain reaction analysis.

Results
After the induction of ICH, some TSP1- or TSP2-immunoreactive microvessels resided around the hematoma for ~ 7 days and extended into a clot thereafter. Cerebral endothelial cells expressed the TSPs. The expression of TSP-1 and TSP-2 mRNA peaked at 4 and 14 days after collagenase-induced ICH, respectively.

Conclusions
Findings in this study suggest that ICH can alter the expression of TSP-1 and TSP-2, which may be involved in modulating angiogenesis in brains following ICH.