Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized, Double-Blind, Placebo-Controlled, International Trial of the Oral IIb/IIIa Antagonist Lotrafiban in Coronary and Cerebrovascular Disease

Background—This is the primary report of the large-scale evaluation of lotrafiban, an orally administered IIb/IIIa receptor antagonist, a unique trial with respect to the platelet antagonist, protocol design, and inclusion of cerebrovascular disease in a significant proportion of patients. Methods and Results—Patients with vascular disease were randomized to lotrafiban 30 or 50 mg BID on the basis of age and predicted creatinine clearance or placebo in addition to aspirin at a dose ranging from 75 to 325 mg/d at the discretion of the physician-investigator. Follow-up was for up to 2 years. The primary end point was the composite of all-cause mortality, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, and urgent revascularization. Of 9190 patients enrolled from 23 countries and 690 hospitals, 41% had cerebrovascular disease at the time of entry, and 59% had coronary artery disease. Death occurred in 2.3% of placebo-assigned patients and 3.0% of lotrafiban-group patients (hazard ratio 1.33, 95% CI 1.03 to 1.72, P =0.026), and the cause of excess death was vascular related. There was no significant difference in the primary end point (17.5% compared with 16.4%, respectively; hazard ratio 0.94, 95% CI 0.85 to 1.03, P =0.19). Serious bleeding was more frequent in the lotrafiban group (8.0% compared with 2.8%; P <0.001). Serious bleeding was more common among patients who received higher doses of aspirin (>162 mg/d), with or without lotrafiban. Conclusions—Lotrafiban, an orally administered platelet glycoprotein IIb/IIIa blocker, induced a 33% increase in death rate, which was vascular in origin and not affected by the type of atherosclerotic involvement at entry to the trial. Although the dose of aspirin was not randomly assigned, the finding of increased bleeding with doses >162 mg/d is noteworthy.
Characterization of a human papillomavirus from epidermodysplasia verruciformis lesions of a patient from upper‐volta

A case of epidermodysplasia verruciformis in a patient from Upper‐Volta is described. Slightly elevated, flat warts were observed on hands, feet, arms and legs, and pityriasis versicolor‐like lesions were found mainly on the trunk. The patient showed no malignant tumors. Histological examination revealed hyperkeratosis, granulosis and moderate acanthosis with large, foamy, basophilic keratinocytes in stratum granulosum and stratum spinosum. Papillomavirus particles could be prepared from these lesions and were differentiated from known papillomavirus types by immune electron microscopy with monospecific antisera and by DNA‐DNA hybridization. The viral DNA was characterized by cleavage with several restriction endonucleases and a physical map of the resulting fragments was established. The virus is designated as HPV 8. Preliminary seroepidemiologic studies with human sera indicate a rather wide distribution of HPV 8. Blot hybridization of DNA from human carcinomas with 32P‐labelled virus DNA detected no HPV 8‐specific sequences.
Axenfeld-Rieger anomaly: a novel mutation in the forkhead box C1 (FOXC1) gene in a 4-generation family.

OBJECTIVE To characterize DNA mutations in a pedigree of Axenfeld-Rieger anomaly (ARA) (Online Mendelian Inheritance of Man 601631), a clinically and genetically heterogeneous, autosomal dominantly inherited disorder associated with anterior chamber abnormalities and glaucoma. DESIGN Observational case-control and DNA linkage and screening studies. PARTICIPANTS Affected (10 cases) and unaffected (5 controls) members of a family with ARA. METHODS Clinical characteristics of ARA were documented by history or physical examination of symptomatic individuals. With their informed consent, a blood sample was collected from each of 10 affected and 5 unaffected family members. DNA was tested for linkage to the IRID1 locus at chromosome 6p25, a known locus for ARA/Rieger syndrome. A candidate gene previously mapped at this locus, FOXC1, was screened for mutations in cases and controls. Main Outcome Measure Linkage of the ARA phenotype at the 6p25 locus and mutation detected in FOXC1. RESULTS Direct sequencing of FOXC1 detected a new mutation, T272C, that segregated with the ARA phenotype in this family and was not detected in DNA from family members without ARA. This mutation, a T-->C transition, is predicted to result in a change of isoleucine to threonine (Ile9lThr) in a highly conserved location within the first helix of the forkhead domain. CONCLUSION Characterization of the FOXC1 mutation in family members with ARA furthers our understanding of the molecular origin of developmental glaucoma and other anterior segment disorders.
Matter Arising: Off-Targets and Genome-Scale RNAi Screens in Drosophila

Recently, the issue of off-target effects (OTEs) associated with long double stranded RNAs (dsRNAs) used in RNAi screens, such as those performed at the Drosophila RNAi Screening Center and other laboratories, has become a focus of great interest and some concern. Although OTEs have been recognized as an important source of false positives in mammalian studies (where short siRNAs are used as triggers), they were generally thought to be inconsequential in Drosophila RNAi experiments because of the use of long dsRNAs. Two recent papers have disputed this contention and show that significant off-target effects can take place with the use of some long dsRNAs in Drosophila cells. Together, these studies provide evidence that OTEs mediated by short homology stretches of 19nt or greater within long dsRNAs can contribute to false positives in Drosophila RNAi screens. Here, we address how widespread the occurrence of OTE is in Drosophila screens, focusing on the DRSC dsRNA collections, and we discuss the implication for the interpretation of results reported in RNAi screens to-date. Lastly, we summarize steps taken by the DRSC to redress that situation and include a set of recommendations to observe in future RNAi screens.
IncobotulinumtoxinA for the Treatment of Platysmal Bands: A Single-Arm, Prospective Proof-of-Concept Clinical Study

BACKGROUND IncobotulinumtoxinA improves the appearance of facial rhytides and the aging neck. OBJECTIVE To investigate the efficacy, safety, and subject satisfaction of incobotulinumtoxinA for platysmal band treatment. METHODS Subjects (n = 23) with 2 to 4 platysmal bands (scoring ≥1 on a newly validated 5-point assessment scale) were enrolled. IncobotulinumtoxinA (15 U) was administered to each band. Assessments, using the 5-point scale, occurred at 6 posttreatment visits over 5 months. Adverse events were recorded and subjects self-assessed the appearance of their platysmal bands versus baseline. RESULTS At maximum tension, a response (≥1-point improvement from baseline score) was observed in 65.2% of subjects 3 (±1) days posttreatment, rising to 100% on Day 8 (±1). The change from baseline in the mean score was significant at each time point, including the final visit (Weeks 20–21). Response rates were higher at maximum tension than at rest. The peak effect occurred later at rest than at maximum tension. No serious adverse event occurred. At maximum tension, 69.6%, 73.9%, and 68.2% of subjects rated their platysmal bands as “improved” or “markedly improved” at Visits 2, 3, and 4, respectively. CONCLUSION IncobotulinumtoxinA is an effective and well-tolerated treatment for platysmal bands, with a rapid onset and long duration of effect.
Dual Inhibition of &bgr;-Adrenergic and Angiotensin II Receptors by a Single Antagonist: A Functional Role for Receptor–Receptor Interaction In Vivo

Background—Although the renin–angiotensin and the &bgr;-adrenergic systems are interrelated, a direct interaction between &bgr;-adrenergic receptors (&bgr;ARs) and angiotensin II type 1 receptors (AT1Rs) has not been identified. Methods and Results—Here, we provide evidence for a functional and physiological interaction between 2 G protein–coupled receptors: the &bgr;AR and the AT1R. Selective blockade of &bgr;ARs in mouse cardiomyocytes inhibits angiotensin-induced contractility with an IC50 that is similar to its inhibition of isoproterenol-mediated contractility. Furthermore, administration of the angiotensin receptor blocker valsartan to intact mice results in a significant reduction in the maximal response to catecholamine-induced elevation of heart rate. The mechanism for this transinhibitory effect of &bgr;-blockers and angiotensin receptor blockers is through receptor–G protein uncoupling; ie, &bgr;-blockers interfere with AT1R-Gq coupling, and valsartan interferes with &bgr;AR-Gs coupling. Finally, we demonstrate that AT1Rs and &bgr;ARs form constitutive complexes that are not affected by ligand stimulation. As a result of these interactions, a single receptor antagonist effectively blocks downstream signaling and trafficking of both receptors simultaneously. Conclusions—We show that direct interactions between &bgr;ARs and AT1Rs may have profound consequences on the overall response to drugs that antagonize these receptors.
Public Cultural Services Recommendation System Architecture

Public cultural sharing service plays an important role in the public cultural platform. The recommender systems can bring users useful cultural resources and information. For safety and security reasons of the cultural resources, the external applications are not allowed to directly access the original resource data stored in the cultural databases by sending recommendation requests. The cultural recommender system needs a way to isolate the cultural resources from the outside while keeping the recommendation services. To address this issue, this paper proposes Representational State Transfer (REST)-based architecture of the cultural recommender system that can provide loosely coupled structures for system modules while maintaining the security access of the cultural resources.
Measuring the under-diversification of socially responsible investments

ABSTRACT This article proposes a straightforward measure of the residual unsystematic risk that a selective portfolio investment strategy, such as socially responsible investment, eventually bears. The model is empirically employed in order to analyse whether the MSCI socially responsible indices bear significant levels of volatility that could be diversified by not imposing social screenings to the set of eligible investments. The study finds that a low but not negligible part of the volatility of the returns could be diversified by not restricting the investment to socially responsible companies. Implications for the socially responsible investing industry and socially responsible investors are discussed.
Optimal energy management for microgrids with cogeneration and renewable energy sources

In this paper, we propose a framework for optimal microgrid energy management considering key features such as utilizing combined heat and power (CHP), handling uncertainties associated with renewable energy sources (RES) and electricity prices, and regulating system voltage levels. Our objective is to minimize microgrid operating cost while maintaining power quality and system security of microgrids. We formulate a two-stage stochastic program to address uncertainties in electricity prices and RES power outputs. The microgrid can maintain both heat and power balances by using multiple distributed energy resources (DER) including CHP, RES, heat storage, batteries, heat boilers, and deferrable loads. Extensive simulation results show that the microgrid can minimize the operating cost and ensure the energy balance and system security by coordinating components in the framework we proposed.
Identification of Predictive Markers of Response to the MEK1/2 Inhibitor Selumetinib (AZD6244) in K-ras–Mutated Colorectal Cancer

Mutant K-ras activity leads to the activation of the RAS/RAF/MEK/ERK pathway in approximately 44% of colorectal cancer (CRC) tumors. Accordingly, several inhibitors of the MEK pathway are under clinical evaluation in several malignancies including CRC. The aim of this study was to develop and characterize predictive biomarkers of response to the MEK1/2 inhibitor AZD6244 in CRC in order to maximize the clinical utility of this agent. Twenty-seven human CRC cell lines were exposed to AZD6244 and classified according to the IC50 value as sensitive (≤0.1 μmol/L) or resistant (>1 μmol/L). All cell lines were subjected to immunoblotting for effector proteins, K-ras/BRAF mutation status, and baseline gene array analysis. Further testing was done in cell line xenografts and K-ras mutant CRC human explants models to develop a predictive genomic classifier for AZD6244. The most sensitive and resistant cell lines were subjected to differential gene array and pathway analyses. Members of the Wnt signaling pathway were highly overexpressed in cell lines resistant to AZD6244 and seem to be functionally involved in mediating resistance by shRNA knockdown studies. Baseline gene array data from CRC cell lines and xenografts were used to develop a k-top scoring pair (k-TSP) classifier, which predicted with 71% accuracy which of a test set of patient-derived K-ras mutant CRC explants would respond to AZD6244, providing the basis for a patient-selective clinical trial. These results also indicate that resistance to AZD6244 may be mediated, in part, by the upregulation of the Wnt pathway, suggesting potential rational combination partners for AZD6244 in CRC. Mol Cancer Ther; 9(12); 3351–62. ©2010 AACR.
Benefits and applications of interdisciplinary digital tools for environmental meta-reviews and analyses

Digitally-aided reviews of large bodies of text-based information, such as academic literature, are growing in capability but are not yet common in environmental fields. Environmental sciences and studies can benefit from application of digital tools to create comprehensive, replicable, interdisciplinary reviews that provide rapid, up-to-date, and policy-relevant reports of existing work. This work reviews the potential for applications of computational text mining and analysis tools originating in the humanities to environmental science and policy questions. Two process-oriented case studies of digitally-aided environmental literature reviews and meta-analyses illustrate potential benefits and limitations. A medium-sized, medium-resolution review (∼8000 journal abstracts and titles) focuses on topic modeling as a rapid way to identify thematic changes over time. A small, high-resolution review (∼300 full text journal articles) combines collocation and network analysis with manual coding to synthesize and question empirical field work. We note that even small digitally-aided analyses are close to the upper limit of what can be done manually. Established computational methods developed in humanities disciplines and refined by humanities and social science scholars to interrogate large bodies of textual data are applicable and useful in environmental sciences but have not yet been widely applied. Two case studies provide evidence that digital tools can enhance insight. Two major conclusions emerge. First, digital tools enable scholars to engage large literatures rapidly and, in some cases, more comprehensively than is possible manually. Digital tools can confirm manually identified patterns or identify additional patterns visible only at a large scale. Second, digital tools allow for more replicable and transparent conclusions to be drawn from literature reviews and meta-analyses. The methodological subfields of digital humanities and computational social sciences will likely continue to create innovative tools for analyzing large bodies of text, providing opportunities for interdisciplinary collaboration with the environmental fields.
Lyapunov rule-based fuzzy control and chaotic anti-control for flexible joint system and analysis of chaotic signal existence effectiveness with experimental validation

This study proposes a novel chaotic anti-control for flexible joint system. The proposed controller is composed of a Lyapunov rule-based fuzzy control and chaotic anti-control for target tracking of the flexible joint manipulator. Chaotic signal is used to study the effect of anti-control to reduce the deflection of flexible joint system and control signal energy. For this purposes the flexible joint has been synchronized with chaotic Lorenz system. In this study on of the Lorenz parameters is changed to analysis the effect of chaotic signals. The results of the proposed approach shows in terms of level of vibration reduction and energy consumption of control signal, we could find an optimum point based on value of Lorenz system parameter. Finally, the efficacy of the proposed method and results of existence of different nonlinearity behavior is validated through experiments on QUANSER's flexible-joint manipulator.
Parallelizing Programs with Recursive Data Structures

A study is made of the problem of estimating interference in an imperative language with dynamic data structures. The authors focus on developing efficient and implementable methods for recursive data structures. In particular, they present interference analysis tools and parallelization techniques for imperative programs that contain dynamically updatable trees and directed acyclic graphs. The analysis methods are based on a regular-expression-like representation of the relationship between accessible nodes in the data structure. They authors have implemented their analysis, and they present some concrete examples that have been processed by this system. >
Inversions over the Terminus Region in Salmonella and Escherichia coli: IS200s as the Sites of Homologous Recombination Inverting the Chromosome of Salmonella enterica Serovar Typhi

ABSTRACT Genomic rearrangements (duplications and inversions) in enteric bacteria such as Salmonella enterica serovar Typhimurium LT2 and Escherichia coli K12 are frequent (10−3 to 10−5) in culture, but in wild-type strains these genomic rearrangements seldom survive. However, inversions commonly survive in the terminus of replication (TER) region, where bidirectional DNA replication terminates; nucleotide sequences from S. enterica serovar Typhimurium LT2, S. enterica serovar Typhi CT18, E. coli K12, and E. coli O157:H7 revealed genomic inversions spanning the TER region. Assuming that S. enterica serovar Typhimurium LT2 represents the ancestral genome structure, we found an inversion of 556 kb in serovar Typhi CT18 between two of the 25 IS200 elements and an inversion of about 700 kb in E. coli K12 and E. coli O157:H7. In addition, there is another inversion of 500 kb in E. coli O157:H7 compared with E. coli K12. PCR analysis confirmed that all S. enterica serovar Typhi strains tested, but not strains of other Salmonella serovars, have an inversion at the exact site of the IS200 insertions. We conclude that inversions of the TER region survive because they do not significantly change replication balance or because they are part of the compensating mechanisms to regain chromosome balance after it is disrupted by insertions, deletions, or other inversions.
Electrotactile and vibrotactile displays for sensory substitution systems

Sensory substitution systems provide their users with environmental information through a human sensory channel (eye, ear, or skin) different from that normally used or with the information processed in some useful way. The authors review the methods used to present visual, auditory, and modified tactile information to the skin and discuss present and potential future applications of sensory substitution, including tactile vision substitution (TVS), tactile auditory substitution, and remote tactile sensing or feedback (teletouch). The relevant sensory physiology of the skin, including the mechanisms of normal touch and the mechanisms and sensations associated with electrical stimulation of the skin using surface electrodes (electrotactile, or electrocutaneous, stimulation), is reviewed. The information-processing ability of the tactile sense and its relevance to sensory substitution is briefly summarized. The limitations of current tactile display technologies are discussed, and areas requiring further research for sensory substitution systems to become more practical are suggested. <<ETX>>
Dynamic changes in replication timing and gene expression during lineage specification of human pluripotent stem cells

Duplication of the genome in mammalian cells occurs in a defined temporal order referred to as its replication-timing (RT) program. RT changes dynamically during development, regulated in units of 400–800 kb referred to as replication domains (RDs). Changes in RT are generally coordinated with transcriptional competence and changes in subnuclear position. We generated genome-wide RT profiles for 26 distinct human cell types, including embryonic stem cell (hESC)-derived, primary cells and established cell lines representing intermediate stages of endoderm, mesoderm, ectoderm, and neural crest (NC) development. We identified clusters of RDs that replicate at unique times in each stage (RT signatures) and confirmed global consolidation of the genome into larger synchronously replicating segments during differentiation. Surprisingly, transcriptome data revealed that the well-accepted correlation between early replication and transcriptional activity was restricted to RT-constitutive genes, whereas two-thirds of the genes that switched RT during differentiation were strongly expressed when late replicating in one or more cell types. Closer inspection revealed that transcription of this class of genes was frequently restricted to the lineage in which the RT switch occurred, but was induced prior to a late-to-early RT switch and/or down-regulated after an early-to-late RT switch. Analysis of transcriptional regulatory networks showed that this class of genes contains strong regulators of genes that were only expressed when early replicating. These results provide intriguing new insight into the complex relationship between transcription and RT regulation during human development.
Male Gender and Low Education with Poor Mental Health Literacy: A Population-based Study

BACKGROUND Both male gender and low socioeconomic status have been related to depression and suicide, but their possible relationship to mental health literacy remains uncertain. The objectives of this study were to assess the level of mental health literacy in rural communities in Japan and to examine related factors. METHODS A population-based cross-sectional study using a questionnaire was conducted. Response rate was 88.2% from 8163 residents aged 30-69 years. The relationships between mental health literacy (including cognition of depression, attitude toward depression, and acceptance of suicide) and demographics, socioeconomic status, and the severity of depression were assessed by logistic regression analysis. RESULTS Of the respondents, 25.2% showed an inadequate cognition of depression, 12.5% showed an inadequate attitude toward depression, and 13.1% showed an acceptance of suicide. Of the complete respondents (65.5%), an inadequate cognition of depression was associated with being male (adjusted odds ratio=1.93, 95% confidence interval: 1.68-2.22), advanced age (2.18, 1.58-3.00), and a lower level of education (1.95, 1.34-2.86); an inadequate attitude toward depression was associated with being male (2.18, 1.82-2.61),a lower education (2.34, 1.38-3.97), and the severity of depression (2.26, 1.54-3.32); and an acceptance of suicide was associated with being male (1.33, 1.13-1.58) and the severity of depression (5.77, 4.20-7.93). CONCLUSIONS Poor mental health literacy related strongly to male gender and a low level of education. According to our results, poor mental health literacy may possibly be a factor contributing to male vulnerability to suicide.