Miracle-dz/UniFAR-FTUs huggingface dataset:
Multisite international collaborative clinical trials in mania.

Multi-regional collaborative clinical trials include those conducted across heterogeneous areas of the world under common protocols. Such trials appear to be driven primarily to provide data required for regulatory approval or licensing of new drug products in a relatively rapid and presumably efficient and cost-effective manner. Commonly, they include underserved populations and areas where costs of trials are lower than in most developed countries. In addition, such studies can potentially make innovative treatments widely and rapidly available in vast, international markets. Other potential benefits to collaborating sites may include diffusion of knowledge and improvement of research skills, as well as improvement of treatment and a broader salutary impact on health services and perhaps on employment opportunities and economic growth (Demol +6; Weihrauch, 1997; Glickman et al. 2009; Gopal et al. 2005; Greco +6; Diniz, 2008; ICH Guideline, 2002; Smulevich et al. 2005; U.S. FDA, 1998). Successful conduct of international trials requires compliance with varying local and international laws, regulations and ethical requirements, and confronting a range of systems of review of ethical aspects of subject recruitment, compensation, consenting procedures, research protocols, and provision of aftercare – all which can add complexity. In addition, there is variance among regions, countries and cultures in levels of education, and in the nature of information, financial inducements, clinical care and aftercare provided to research subjects. Complexities arise also from culture-dependent conceptualizations of mental disorders, criteria for diagnosis, and efforts at validating, interpreting and scoring of symptom ratings designed to characterize changes during treatment, and methods for detecting adverse events. In the continuing quest to define core or universal features of psychiatric disorders, it is crucial to consider the anthropological and cultural context in which they develop and are modified (Karno +6; Jenkins, 1993; Lopez-Ibor, 2003; …
Genetic Distribution of the Cowpea (Vigna Unguiculata (L.) Walp) Bruchid (Callosobruchus Maculatus F., Coleoptera, Bruchidae) Populations in Different Agro-Ecological Areas of West Africa

Cowpea [(Vigna unguiculata L.) Walp. (Fabaceae)] is the most important food legume grown throughout West Africa. The seeds of this legume protein source are the least expensive for most African populations. However, cowpea production is severely limited by the losses (60-70%) caused by Callosobruchus maculatus F. (Coleoptera: Bruchidae). Whereas many studies have been devoted to the ecology of these bruchids and allowed to distinguish physiotypes and morphotypes, few studies have been conducted on the spatial and temporal structuring of populations of the weevil and migration patterns between agro-ecological areas. By using molecular data; (a combined set of a mitochondrial and ribosomal genes), this study aims to identify genetic diversity and phylogenetic affinities of allopatric C. maculatus populations within the West Africa sub-region. Climate influence (Agro-ecological conditions) was also tested. The results reveal several ecotypes circulate in the West Africa sub-region. Among samples, the genetic distances measured on the total alignment of CytB + 28S (852 bp) ranged between 0 and 0.047 and show clearly fall in three classes. The phylogenetic reconstructions show clearly that the genetic structure of the C. maculatus populations is strongly influenced by the agro-ecological zone.
The N Terminus of Kaposi's Sarcoma-associated Herpesvirus G Protein-coupled Receptor Is Necessary for High Affinity Chemokine Binding but Not for Constitutive Activity*

Kaposi's sarcoma-associated herpesvirus (KSHV) contains a gene encoding a G protein-coupled receptor (KSHV-GPCR) that is homologous to mammalian chemokine receptors. KSHV-GPCR signals constitutively (in an agonist-independent manner) via the phosphoinositide-inositol 1,4,5-trisphosphate pathway. Because it has been proposed that the N terminus (N-TERM) of other GPCRs may act as tethered agonists, we determined whether the N-TERM of KSHV-GPCR is necessary for constitutive signaling activity or ligand binding, or both. We show that replacement of the entire N-TERM of KSHV-GPCR with those of two other GPCRs, deletion of residues within the N-TERM, and disruption of a putative disulfide bond that may hold the N-TERM in close proximity to extracellular loop 3 do not affect constitutive signaling activity but decrease chemokine binding. There were differences in the effects of mutation of the N-TERM on binding of the chemokines growth-related oncogene α, which is an agonist, and interferon-γ-inducible protein-10, which is an inverse agonist. The effects on chemokine binding were accompanied by changes in chemokine regulation of KSHV-GPCR signaling. We conclude that the N-TERM is not necessary for constitutive KSHV-GPCR signaling, i.e. the N-TERM is not a tethered agonist, but plays a crucial role in binding of chemokine ligands and of chemokine regulation of KSHV-GPCR signaling.
Developmental Profile of Ion Channel Specializations in the Avian Nucleus Magnocellularis

Ultrafast and temporally precise action potentials (APs) are biophysical specializations of auditory brainstem neurons; properties necessary for encoding sound localization and communication cues. Fundamental to these specializations are voltage dependent potassium (KV) and sodium (NaV) ion channels. Here, we characterized the functional development of these ion channels and quantified how they shape AP properties in the avian cochlear nucleus magnocellularis (NM). We report that late developing NM neurons (embryonic [E] days 19–21) generate fast APs that reliably phase lock to sinusoidal inputs at 75 Hz. In contrast, early developing neurons (<E12) have slower and less reliable APs that preferentially fire to lower frequencies (5–10 Hz). With development, the membrane time constant of NM neurons became faster, while input resistance and capacitance decreased. Change in input resistance was due to a 2-fold increase in KV current from E10 to E21 and when high-voltage activated potassium (K+HVA) channels were blocked, APs for all ages became significantly slower. This was most evident for early developing neurons where the ratio of K+HVA current accounted for ~85% of the total KV response. This ratio dropped to ~50% for late developing neurons, suggesting a developmental upregulation of low-voltage activated potassium (K+LVA) channels. Indeed, blockade of K+LVA eliminated remaining current and increased neural excitability for late developing neurons. We also report developmental changes in the amplitude, kinetics and voltage dependence of NaV currents. For early developing neurons, increase in NaV current amplitude was due to channel density while channel conductance dominated for late developing neurons. From E10 to E21, NaV channel currents became faster but differed in their voltage dependence; early developing neurons (<E16) had similar NaV channel inactivation voltages while late developing NM neurons (>E19) contained NaV channels that inactivate at more negative voltages, suggesting alterations in NaV channel subtypes. Taken together, our results indicate that the refinement of passive and active ion channel properties operate differentially in order to develop fast and reliable APs in the avian NM.
Alternative Splicing and mRNA Levels of the Disease Resistance Gene RPS 4 Are Induced during Defense Responses 1 [ W ] [ OA ]

The Arabidopsis (Arabidopsis thaliana) disease resistance protein RESISTANCE TO PSEUDOMONAS SYRINGAE4 (RPS4) activates defenses in response to bacterial pathogens expressing avrRps4 in a gene-for-gene specific manner. The RPS4 gene produces multiple transcripts via alternative splicing of two regular introns flanking exon 3 and a cryptic intron within exon 3. We showed previously that RPS4-mediated resistance requires the combined presence of transcripts encoding both full-length and truncated open reading frames. Here, we demonstrate that alternative splicing of RPS4 undergoes dynamic changes specifically during the resistance response. Furthermore, RPS4 expression was induced by the presence of AvrRps4 in an EDS1-dependent manner. Interestingly, inducible alternative splicing was not limited to the avrRps4-RPS4 interaction, indicating that regulation of alternative splicing may be a general response to prime the plant stress response system. Introndeficient transgenes lacking only one intron were previously shown to be nonfunctional. Here, we establish quantitatively that the absence of one intron had no effect on the splicing frequency of remaining introns. Given the lack of functionality of single intron-deficient transgenes, this suggests that the products of individual transcripts have distinct functions during RPS4triggered resistance. Transient expression of truncated RPS4 proteins in Nicotiana benthamiana induced hypersensitive response-like cell death in the absence of AvrRps4. Interestingly, different truncated proteins had markedly differing stability. In summary, RPS4 function is regulated at multiple levels, including gene expression, alternative splicing, and protein stability, presumably to fine-tune activity and limit damage inflicted by activated RPS4 protein.
Bounding the power of preemption in randomized scheduling

We study on-line scheduling in overloaded systems. Requests for jobs arrive one by one as time proceeds; the serving agents have limited capacity and not all requests can be served. Still, we want to serve the "best" set of requests according to some criterion. In this situation, the ability to preempt (i.e., abort) jobs in service in order to make room for better jobs that would otherwise be rejected has proven to be of great help in some scenarios. We show that, surprisingly, in many other scenarios this is not the case. In a simple, generic model, we prove a polylogarithmic lower bound on the competitiveness of randomized and preemptive on-line scheduling algorithms. Our bound applies to several recently studied problems. In fact, in certain scenarios our bound is quite close to the competitiveness achieved by known deterministic, nonpreemptive algorithms.
‘My home and my school’: examining immigrant adolescent narratives from the critical sociocultural perspective

Privileging the voices of 12 recent Chinese immigrant adolescents, this multiple‐case narrative study examined their home and school experiences from the critical sociocultural perspective. The adolescent stories about home testified to the significant influence of immigrant poverty, parental sacrificial altruism, and disciplinary Chinese parenting in their academic achievement. The adolescent experiences at school revealed their appreciation of Canadian liberal education, their perception of ethnic peer divides, and their concerns about the ineffectiveness and the negative psychological consequences of the ESL (English as a Second Language) programming. Locating the adolescent narratives in the hierarchical power of domination in Canadian society, this article challenges mainstream educational institutions to address the changing nature of urban Canadian classrooms, structurally and ideologically representing the strengths of cultural diversity.
Can Performance Appraisal Systems Inspire Intrinsically Motivated Employees?

Can a performance appraisal system (PAS) elicit better performance from an intrinsically motivated workforce? By explicitly linking extrinsic rewards to performance, a PAS might actually discourage the work effort of the primarily intrinsically motivated federal workforce. Data from the 2000 Merit Principles Survey show that few federal employees believe that the PAS increases their productivity. Logit analysis confirms that intrinsically motivated employees are more skeptical of the effectiveness of PAS than are extrinsically motivated employees who are demographically similar, work in similar positions, and have similar beliefs about the fairness of the system and the probability of being rewarded for superior performance.
Clinical, actuarial and dynamic risk assessment of sexual offenders: Why do things keep changing?

Abstract This paper reviews the changes in risk assessment procedures for sexual offenders over the last 15 years from the viewpoint of two active participants in that change. Best practices with this target group have evolved at a dizzying pace, leaving many practitioners and programme managers uncertain about which tests or procedures they should use and, frankly, wondering why things keep changing. We view this ongoing evolution as very positive. Compared to the early 1990s, evaluators now have better knowledge of the static and dynamic factors associated with sexual recidivism, and a number of empirically validated risk assessment tools. We describe the various risk assessment procedures we have introduced (e.g. STATIC-99, SONAR, STABLE-2007/ACUTE-2007), the reasons why practices have changed and the reasons why practices will continue to change.
A qualitative study of the food-related experiences of rural village shop customers.

BACKGROUND In the UK, although food choice in urban contexts has been widely studied, far less empirical information has been gathered from rural settings. With the closure of local services, some rural dwellers were believed to experience difficulties in meeting healthy eating recommendations. The present study aimed to explore perceptions of village store users. METHODS Semi-structured, in-depth interviews were conducted individually with 40 adults who were frequent users of rural village shops in Norfolk, UK. Participants were purposively selected to ensure that a wide demographic cross-section of customers was obtained. Interviews focused upon food choice strategies; attitudes towards rural food retail; and the provision of healthy foods. Interviews were transcribed verbatim and analysed qualitatively, using an established interpretative phenomenological approach. RESULTS Four main themes emerged as drivers of food choice in rural villages: (1) village store as icon, which described how the perceived centrality of village shops influenced food choices; (2) village store as a service provider, which described top-up shopping behaviours; (3) alternative food sources, which described store users desires for local foods and their attitudinal conflicts towards supermarkets; and (4) lifestyle factors, which described the influence of factors such as time pressures, access to cars and family structures. CONCLUSIONS Food choices were strongly influenced by the distinctive characteristics of the rural environment. Village shops were seen as important for community identity ('rural idyll'), as well as providing access to food and services. However, desires were made apparent for a greater range of healthy, fresh and locally-sourced foods.
Carbonic anhydrases in meningiomas: association of endothelial carbonic anhydrase II with aggressive tumor features.

OBJECT Carbonic anhydrase (CA) II and IX are enzymes involved in pH homeostasis and have been shown to be upregulated in several types of cancer. In this study, the authors evaluate the expression of CA II and IX in meningiomas and assess their relationship to patient age, tumor type and grade, tumor sex hormone receptor status, tumor cell proliferation, and tumor recurrence. METHODS This study was conducted in consecutive patients who underwent meningioma surgeries at Tampere University Hospital between 1989 and 1999. The expression of CA II and IX was studied immunohistochemically using a tissue microarray technique and specific antibodies. RESULTS Immunohistological staining with CA II and IX was assessed in 443 primary and 67 recurrent tumor specimens. Of these samples, 455 were benign (WHO Grade I), 49 atypical (Grade II), and 6 malignant (Grade III). Endothelial cells in 14.8% of the tumors stained positively for CA II. Tumor cells were positive for CA IX in 11.6% of the cases. Endothelial CA II expression correlated with increasing histological grade (p=0.002), and tumor proliferation rates were higher in CA II+ versus CA II- cases (p=0.002). Androgen receptor-negative tumors were found to be CA II+ significantly more often than androgen receptor-positive tumors (p=0.001). No associations were found with the CA IX enzyme. CONCLUSIONS Carbonic anhydrase II positivity in the endothelium was associated with cell proliferation and malignancy grade. These results suggest that CA II expression is associated with malignant progression of meningiomas and could thus be a target molecule for anticancer therapy.
High levels of β‐catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway

Periodontal ligament stem cells (PDLSCs), a new population of mesenchymal stem cells (MSCs), have been isolated from the periodontal ligament (PDL). The capacity of multipotency and self‐renewal makes them an excellent cell source for bone regeneration and repair. However, their bone‐regeneration ability could be awakened in inflammatory microenvironments, which may be the result of changes in their differentiation potential. Recently, genetic evidences has shown that the Wnt pathway plays an important role in bone homeostasis. In this study we have determined the specific role of β‐catenin in osteogenic differentiation of PDLSCs obtained from inflammatory microenvironments (P‐PDLSCs). The inflammatory microenvironment, while inhibiting osteogenic differentiation potential, promotes proliferation of MSCs. A higher the level of β‐catenin in P‐PDLSCs than in H‐PDLSCs (PDLSCs obtained from a healthy microenvironment) resulted in the same disparity in canonical Wnt signaling pathway activation between each cell type. Here we show that activation of β‐catenin suppresses the noncanonical Wnt/Ca2+ pathway, leading to increased proliferation but reduced osteogenic differentiation of P‐PDLSCs. Downregulation of the levels of β‐catenin by treatment with dickkopf‐1 (DKK‐1) leads to activation of the noncanonical Wnt/Ca2+ pathway, which, in turn, results in the promotion of osteogenic differentiation in P‐PDLSCs. Interestingly, β‐catenin can affect both the canonical Wnt/β‐catenin pathway and the noncanonical Wnt/Ca2+ pathway. Our data indicate that β‐catenin plays a central role in regulating osteogenic differentiation of MSCs in inflammatory microenvironments. Given the important role of Wnt signaling in osteogenic differentiation, it is possible that agents that can modify this pathway may be of value in bone regeneration by MSCs in chronic inflammatory microenvironments. © 2011 American Society for Bone and Mineral Research
The oscillatory damped behaviour of incommensurate double-walled carbon nanotubes

The mechanical properties of sliding carbon nanotubes have been investigated by classical molecular dynamics simulations in the canonical ensemble. In particular we have studied damped oscillations in the separation between the centres of mass of the inner and outer tubes of double-walled carbon nanotubes (DWCN). Incommensurate DWCNs forming (7, 0)@(9, 9) structures were simulated for systems at 298.15 K with axial lengths from 12.21 to 98.24 nm. The oscillations exhibited frequencies in the range of gigahertz with the frequency decreasing as the length of the system increases. The time until oscillations become negligible exhibited a nearly linear dependence on the length of the system. Two macroscopic models were developed in order to understand the forces involved in terms of macroscopic properties like friction and shear. The first model considered constant restoring forces during the whole event, while in the second the value of these constant restoring forces depended on the initial conditions of each oscillation. Both models reproduced the oscillations quite well, while the second model allows us to predict the dynamic shear strength in terms of the axial length of the system for tubes with the same diameters. The calculated dynamic shear strength exhibited monotonic behaviour with an inverse dependence on the length of the system. For systems with unequal axial lengths, the restoring force, which drives the oscillation, is reduced compared to the system with equal lengths, regardless of whether the outer nanotube is longer or shorter.
The Structure of Group Cohesion

Group cohesion is an important construct in understanding the behavior of groups. However, there has been ongoing controversy on how to define and measure this construct. Central to this debate is the structure of cohesion. The authors critically review the literature on unidimensional and multidimensional models of cohesion and describe cohesion as a multidimensional construct with primary and secondary dimensions. Primary dimensions are applicable to describing the cohesiveness of all or most types of groups, whereas secondary dimensions are applicable to describing the cohesiveness of specific types of groups. Viewing group cohesion as consisting of primary and secondary dimensions is discussed.
Application of CFD in Building Performance Simulation for the Outdoor Environment: an Overview

This article provides an overview of the application of computational fluid dynamics (CFD) in building performance simulation for the outdoor environment, focused on four topics: (1) pedestrian wind environment around buildings, (2) wind-driven rain on building facades, (3) convective heat transfer coefficients at exterior building surfaces and (4) air pollutant dispersion around buildings. For each topic, its background, the need for CFD, an overview of some past CFD studies, a discussion about accuracy and some perspectives for practical application are provided. This article indicates that for all four topics, CFD offers considerable advantages compared with wind tunnel modelling or (semi-)empirical formulae because it can provide detailed whole-flow field data under fully controlled conditions and without similarity constraints. The main limitations are the deficiencies of steady Reynolds-averaged Navier–Stokes modelling, the increased complexity and computational expense of large eddy simulation and the requirement of systematic and time-consuming CFD solution verification and validation studies.
Personality Theories for the 21st Century

Classic personality theories, although intriguing, are outdated. The five-factor model of personality traits reinvigorated personality research, and the resulting findings spurred a new generation of personality theories. These theories assign a central place to traits and acknowledge the crucial role of evolved biology in shaping human psychology; they also address the modifying influences of the social and cultural environment. Teachers can and should teach “personality theories” as a science course, not a history course.
Talkin’ ‘bout a revolution: the social, political, and fantasmatic logics of education policy

This paper provides a critical analysis of the Australian government’s education revolution policy as promulgated in the media release document, Quality Education: The Case for an Education Revolution in our Schools. It seeks to problematize the government’s claim to marry quality and equity, via an analysis of the discursive strategies of the Australian government’s revolution talk. My analysis draws on the work of political theorists Jason Glynos and David Howarth and their synthesis of key ideas from Laclau and Mouffe’s discourse theory and Lacanian psychoanalytic theory into a framework of explanatory ‘logics. ’ This framework provides conceptual tools for conducting critical policy analysis, including: characterizing a discursive regime on a synchronic plane; accounting for its constitution, reproduction, and/or subversion on a diachronic plane; and explaining the ways in which it grips or seduces subjects at a nonrational level. Overall, the analysis of the education revolution in this paper demonstrates the value of this framework of explanatory logics for education policy analysis, in the process shedding some new light on the Australian government’s education revolution policy agenda.