Miracle-dz/UniFAR-FTUs huggingface dataset:
TOX4 and NOVA1 Proteins Are Partners of the LEDGF PWWP Domain and Affect HIV-1 Replication

PWWP domains are involved in the chromatin attachment of several proteins. They bind to both DNA and proteins and their interaction with specific histone methylation marks define them as a new class of histone code readers. The lens epithelium derived growth factor (LEDGF/p75) contains an N-terminal PWWP domain necessary for its interaction with chromatin but also a C-terminal domain which interacts with several proteins, such as lentiviral integrases. These two domains confer a chromatin-tethering function to LEDGF/p75 and in the case of lentiviral integrases, this tethering participates in the efficiency and site selectivity of integration. Although proteins interacting with LEDGF/p75 C-terminal domain have been extensively studied, no data exist about partners of its PWWP domain regulating its interaction with chromatin. In this study, we report the identification by yeast-two-hybrid of thirteen potential partners of the LEDGF PWWP domain. Five of these interactions were confirmed in mammalian cells, using both a protein complementation assay and co-immunoprecipitation approaches. Three of these partners interact with full length LEDGF/p75, they are specific for PWWP domains of the HDGF family and they require PWWP amino acids essential for the interaction with chromatin. Among them, the transcription activator TOX4 and the splicing cofactor NOVA1 were selected for a more extensive study. These two proteins or their PWWP interacting regions (PIR) colocalize with LEDGF/p75 in Hela cells and interact in vitro in the presence of DNA. Finally, single round VSV-G pseudotyped HIV-1 but not MLV infection is inhibited in cells overexpressing these two PIRs. The observed inhibition of infection can be attributed to a defect in the integration step. Our data suggest that a regulation of LEDGF interaction with chromatin by cellular partners of its PWWP domain could be involved in several processes linked to LEDGF tethering properties, such as lentiviral integration, DNA repair or transcriptional regulation.
Multiple Identities and Work Motivation: The Role of Perceived Compatibility between Nested Organizational Units

This study examines the role of perceived compatibility between nested organizational units in identification and work motivation. A survey was conducted in German pharmaceutical stores that had joined a large cooperative network several months before the investigation. Employees judged how compatible the network was with their individual stores on four dimensions (ensuring future, preserving tradition, preserving distinctiveness, and maintaining autonomy). Further, employees indicated their identifications with store and network and their intentions to exert effort on behalf of these units (store motivation and network motivation, respectively). As predicted, perceived compatibility correlated positively with both network identification and network motivation. It also moderated the correlations between store identification and network identification as well as between store motivation and network motivation. Several underlying mechanisms are discussed (e.g. evaluation of store and network, social projection). Overall, perceived compatibility between organizational units appears to be a crucial but under-researched factor affecting identification and motivation at work.
Problem Structure in the Presence of Perturbations

Recent progress on search and reasoning procedures has been driven by experimentation on computationally hard problem instances. Hard random problem distributions are an important source of such instances. Challenge problems from the area of finite algebra have also stimulated research on search and reasoning procedures. Nevertheless, the relation of such problems to practical applications is somewhat unclear. Realistic problem instances clearly have more structure than the random problem instances, but, on the other hand, they are not as regular as the structured mathematical problems. We propose a new benchmark domain that bridges the gap between the purely random instances and the highly structured problems, by introducing perturbations into a structured domain. We will show how to obtain interesting search problems in this manner, and how such problems can be used to study the robustness of search control mechanisms. Our experiments demonstrate that the performance of search strategies designed to mimic direct constructive methods degrade surprisingly quickly in the presence of even minor perturbations.
Deep Asymmetric Multi-task Feature Learning

We propose Deep Asymmetric Multitask Feature Learning (Deep-AMTFL) which can learn deep representations shared across multiple tasks while effectively preventing negative transfer that may happen in the feature sharing process. Specifically, we introduce an asymmetric autoencoder term that allows reliable predictors for the easy tasks to have high contribution to the feature learning while suppressing the influences of unreliable predictors for more difficult tasks. This allows the learning of less noisy representations, and enables unreliable predictors to exploit knowledge from the reliable predictors via the shared latent features. Such asymmetric knowledge transfer through shared features is also more scalable and efficient than inter-task asymmetric transfer. We validate our Deep-AMTFL model on multiple benchmark datasets for multitask learning and image classification, on which it significantly outperforms existing symmetric and asymmetric multitask learning models, by effectively preventing negative transfer in deep feature learning.
Effects of warm-up before eccentric exercise on indirect markers of muscle damage.

PURPOSE To test whether active and passive warm-up conducted before eccentric exercise attenuates clinical markers of muscle damage. METHODS Untrained subjects were exposed to one of five conditions: low-heat passive warm-up (N = 10), high-heat passive warm-up (N = 4), or active warm-up (N = 9), preceding eccentric exercise; eccentric exercise without warm-up (N = 10); or high-heat passive warm-up without eccentric exercise (N = 10). Passive warm-up of the elbow flexors was achieved using pulsed short-wave diathermy, and active warm-up was achieved by concentric contraction. Creatine kinase (CK) activity, strength, range of motion, swelling, and muscle soreness were observed before treatment (baseline) and 24, 48, 72, and 168 h after treatment. RESULTS High-heat passive warm-up without eccentric exercise did not affect any marker of muscle damage and was used as our control group. Markers of muscle damage were not different between groups that did or did not conduct warm-up before eccentric exercise. The active warm-up and eccentric groups exhibited a greater circumferential increase than controls (P < 0.0002), however, that was not observed after passive warm-up. Additionally, the active warm-up group exhibited a greater CK response than controls at 72 h (P < 0.05). The high-heat passive warm-up before eccentric exercise group exhibited significant change from controls at the least number of time points, but due to a small sample size (N = 4), these data should be viewed as preliminary. CONCLUSION Our observations suggest that passive warm-up performed before eccentric exercise may be more beneficial than active warm-up or no warm-up in attenuating swelling but does not prevent, attenuate, or resolve more quickly the other clinical symptoms of eccentric muscle damage as produced in this study.
What makes an individual the leader of its group? An evolutionary concept of distance regulation and leadership

It is argued that leading is the outcome of an asymmetry between two or more individuals regulating their distance to one another and to other resources. The asymmetry which decides on leader and follower(s) is a momentary or permanent difference in the so-called critical distance to a particular partner. Beyond this distance, following the partner is more profitable in terms of reproductive fitness than staying back when he leaves or leaving when he stays. The individual with the greater critical distance to the partner can tolerate greater distances from him and thus will be the leader. The basic evolutionary model that is outlined allows us to understand various forms of leading and to specify some characteristics that enhance the probability of an individual to be the leader of a group, i.e. its “leadership”. For achieving a broader unifying framework that covers more than the most simple forms of leading, extensions of the basic model to several partners, objects or places, to manipulation of the partners' “landscape” of expected fitness payoffs, to time rather than space, and to prior negotiations on goals of joint action become necessary. Such extensions are outlined and discussed.
Bacterial RNA Polymerase-DNA Interaction—The Driving Force of Gene Expression and the Target for Drug Action

DNA-dependent multisubunit RNA polymerase (RNAP) is the key enzyme of gene expression and a target of regulation in all kingdoms of life. It is a complex multifunctional molecular machine which, unlike other DNA-binding proteins, engages in extensive and dynamic interactions (both specific and nonspecific) with DNA, and maintains them over a distance. These interactions are controlled by DNA sequences, DNA topology, and a host of regulatory factors. Here, we summarize key recent structural and biochemical studies that elucidate the fine details of RNAP-DNA interactions during initiation. The findings of these studies help unravel the molecular mechanisms of promoter recognition and open complex formation, initiation of transcript synthesis and promoter escape. We also discuss most current advances in the studies of drugs that specifically target RNAP-DNA interactions during transcription initiation and elongation.
Visual and semiquantitative analysis of 18F-fluorodeoxyglucose positron emission tomography using a partial-ring tomograph without attenuation correction to differentiate benign and malignant pulmonary nodules.

OBJECTIVE Many studies have reported the use of attenuation-corrected positron emission tomography with 18F-fluorodeoxyglucose (FDG PET) with full-ring tomographs to differentiate between benign and malignant pulmonary nodules. We sought to evaluate FDG PET using a partial-ring tomograph without attenuation correction. METHODS A retrospective review of PET images from 77 patients (range 38-84 years of age) with proven benign or malignant pulmonary nodules was undertaken. All images were obtained using a Siemens/CTI ECAT ART tomograph, without attenuation correction, after 185 MBq 18F-FDG was injected. Images were visually graded on a 5-point scale from "definitely malignant" to "definitely benign," and lesion-to-background (LB) ratios were calculated using region of interest analysis. Visual and semiquantitative analyses were compared using receiver operating characteristic analysis. RESULTS Twenty lesions were benign and 57 were malignant. The mean LB ratio for benign lesions was 1.5 (range 1.0-5.7) and for malignant lesions 5.7 (range 1.2-14.1) (p < 0.001). The area under the ROC curve for LB ratio analysis was 0.95, and for visual analysis 0.91 (p = 0.39). The optimal cut-off ratio with LB ratio analysis was 1.8, giving a sensitivity of 95% and a specificity of 85%. For lesions thought to be "definitely malignant" on visual analysis, the sensitivity was 93% and the specificity 85%. Three proven infective lesions were rated as malignant by both techniques (LB ratio 2.6-5.7). CONCLUSIONS FDG PET without attenuation correction is accurate for differentiating between benign and malignant lung nodules. Results using simple LB ratios without attenuation correction compare favourably with the published sensitivity and specificity for standard uptake ratios. Visual analysis is equally accurate.
Higher order lipase gene association with plasma triglycerides Published, JLR Papers in Press, June 16, 2005. DOI 10.1194/jlr.M500042-JLR200

Lipoprotein lipase, HL, and endothelial lipase (EL) are proteoglycan-bound enzymes that regulate plasma lipoprotein levels through coordinated triglyceride (TG) lipase and phospholipase activity. We hypothesized that single nucleotide polymorphisms (SNPs) in lipase genes would have higher order impact on plasma lipoproteins beyond the influence of individual SNPs. In a sample of asymptomatic Caucasian subjects (n = 738), we used a two-stage approach, first identifying groups of subjects with similar multilocus lipase genotypes and then characterizing the relationships between genotype groups and plasma lipids. Using complementary methods, including a permutation test procedure and a mixed-effects modeling approach, we found a higher order interaction between four SNPs in three lipase genes (EL 2,237 3′ untranslated region, EL Thr111Ile, HL −514C/T, and LPL Hind III) and plasma TG levels. Subjects who were heterozygous for all four lipase SNPs had significantly higher plasma TG levels beyond the effect of individual lipase SNPs and environmental factors, even after correcting for multiple comparisons. In conclusion, lipase genes had synergistic association with plasma TG beyond individual gene effects. Higher order multilocus genotype contributions to dyslipidemia and atherosclerotic cardiovascular disease need to be considered a priori because they may have an important effect even in the absence of significant main effects of the individual genes.
A model of plant strategies in fluvial hydrosystems

1. We propose a model of plant strategies in temperate fluvial hydrosystems that considers the hydraulic and geomorphic features that control plant recruitment, establishment and growth in river floodplains. 2. The model describes first how the disturbance gradient and the grain-size of the river bed load affect the relative proportion of erosion and deposition processes, and how the frequency of flood disturbance affects the intensity of such processes. 3. Secondly, the model predicts plant strategies according to direct and indirect effects of floods (disturbances through erosion versus deposition processes, and associated nutrient excess or limitation). 4. The relevance of the model as a prediction tool is discussed. Some proposals are made to validate the model, and traits are proposed that should be considered in future research for improving the predicting value of the model.
Functional Status of Peripheral Blood T-Cells in Ischemic Stroke Patients

Stroke is a major cause of disability and leading cause of death in the northern hemisphere. Only recently it became evident that cerebral ischemia not only leads to brain tissue damage and subsequent local inflammation but also to a dramatic loss of peripheral blood T-cells with subsequent infections. However, only scarce information is available on the activation status of surviving T cells. This study therefore addressed the functional consequences of immunological changes induced by stroke in humans. For this purpose peripheral blood T-cells were isolated from 93 stroke patients and the expression of activation makers was determined. In addition ex vivo stimulation assays were applied to asses the functionality of T cells derived from blood of stroke patients. Compared to healthy controls, stroke patients demonstrated an enhanced surface expression of HLA-DR (p<0.0001) and CD25 (p = 0.02) on T cells, revealing that stroke leads to T cell activation, while CTLA-4 remained undetectable. In vitro studies revealed that catecholamines inhibit CTLA-4 upregulation in activated T cells. Ex vivo, T cells of stroke patients proliferated unimpaired and released increased amounts of the proinflammatory cytokine TNF-α (p<0.01) and IL-6 (p<0.05). Also, in sera of stroke patients HMGB1 concentrations were increased (p = 0.0002). The data demonstrate that surviving T cells in stroke patients remain fully functional and are primed towards a TH1 response, in addition we provide evidence that catecholamine mediated inhibition of CTLA-4 expression and serum HMGB1 release are possible mediators in stroke induced activation of T cells.
Thyroidectomy in the professional singer-neural monitored surgical outcomes.

BACKGROUND Voice changes commonly occur from thyroidectomy and may be due to neural or nonneural causes. Such changes can be a source of significant morbidity for any patient, but thyroidectomy in the professional singer carries special significance. We test the hypothesis that the career of singers and professional voice users is not impaired after neural monitored thyroid surgery. METHODS A quantitative analysis of pre- and postoperative neural monitored thyroid surgery voice outcomes utilizing three validated vocal instruments-Voice Handicap Index (VHI), Singing Voice Handicap Index (SVHI), and Evaluation of Ability to Sing Easily (EASE)-in a unique series of professional singers/voice users was performed. Additional quantitative analysis related to final intraoperative electromyography (EMG) amplitude, the time to return to performance, and vocal parameters affected during this interval was performed. RESULTS Twenty-seven vocal professionals undergoing thyroidectomy were identified, of whom 60% had surgery for thyroid cancer. Pre- and postsurgery flexible fiberoptic laryngeal exams were normal in all patients. Return to performance rate was 100%, and mean time to performance was 2.26 months (±1.61). All three vocal instrument mean scores, pre-op vs. post-op, were unchanged: VHI, 4.15 (±5.22) vs. 4.04 (±3.85), p=0.9301; SVHI, 11.26 (±14.41) vs.12. 07 (±13.09), p=0.8297; and EASE, 6.19 (±9.19) vs. 6.00 (±7.72), p=0.9348. The vocal parameters most affected from surgery until first performances were vocal fatigue (89%), high range (89%), pitch control and modulation (74%), and strength (81%). Final mean intraoperative EMG amplitude was within normal limits for intraoperative stimulation and had no relationship with time to first professional performance (p=0.7199). CONCLUSIONS Neural monitored thyroidectomy, including for thyroid malignancy, in professional voice users is safe without any changes in three different voice/singing instruments, with 100% return to performance. Intraoperative EMG data at the conclusion of surgery and postoperative laryngeal exam were normal in all patients. Specific vocal parameters are transiently affected during the postoperative recovery phase, which is important to outline in the consent process of this unique patient population and may provide insight into the physiologic state of the larynx subsequent to thyroid surgery.
Dual role of DNA methylation inside and outside of CTCF-binding regions in the transcriptional regulation of the telomerase hTERT gene

Expression of hTERT is the major limiting factor for telomerase activity. We previously showed that methylation of the hTERT promoter is necessary for its transcription and that CTCF can repress hTERT transcription by binding to the first exon. In this study, we used electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) to show that CTCF does not bind the methylated first exon of hTERT. Treatment of telomerase-positive cells with 5-azadC led to a strong demethylation of hTERT 5′-regulatory region, reactivation of CTCF binding and downregulation of hTERT. Although complete hTERT promoter methylation was associated with full transcriptional repression, detailed mapping showed that, in telomerase-positive cells, not all the CpG sites were methylated, especially in the promoter region. Using a methylation cassette assay, selective demethylation of 110 bp within the core promoter significantly increased hTERT transcriptional activity. This study underlines the dual role of DNA methylation in hTERT transcriptional regulation. In our model, hTERT methylation prevents binding of the CTCF repressor, but partial hypomethylation of the core promoter is necessary for hTERT expression.
Mobile Telecommunications and M-Commerce Applications

The World Wide Web (WWW) and Web browser software brought mass market accessibility to the Internet. Riding on this ubiquity and reach is electronic commerce (e-commerce) in its many forms: inter-business dealing, intra-organization transactions and business-to-consumer trade, and so forth. E-commerce has witnessed impressive growth and continues to be a significant propellant of Internet progress. Participants have, however, hitherto been essentially tethered to fixed line connections. The development of novel wireless services and mobile adaptations of familiar applications (Ghini, 2000) is fueled by demand from increasingly nomadic users looking to access familiar online facilities, and the steady convergence of telecommunications and computing technologies (Messerschmitt, 1996). Wireless telecommunications was conceived in the 1980s to carry voice, but has evolved to become data bearer, including Internet communications. The cellular telephone is now commonplace and more personal digital assistants (PDAs), hand-held computers and the like are sporting cellular radio connectivity. These devices form a sizable platform for deploying m-commerce applications. M-commerce refers to the ability to browse, interact with and make payment for goods and services directly from mobile terminals such as cell phones, PDAs and portable computers (Tan, 2002). Industry forecast statistics point to exponential growth in the sector: • Worldwide shipment of Web-enabled wireless devices rose 796% in 2000 over 1999 and consumer transactions committed from such terminals will total US $1.8 trillion worldwide by 2005 (Source: Gartner Group). • International wireless data market was expected to grow from 170 million to more than 1.3 billion subscribers between 2000–2004, equipping themselves with 1.5 billion wireless-capable handsets and other Internet appliances by end of 2004 (Source: Cahners In-Stat Group). • Wireless Internet users in the Asia-Pacific region alone will rise 10-fold from 20 to 216.3 million between 2000–2007 (Source: Strategis Group).
Diagnosis of Early Alzheimer's Disease Based on EEG Source Localization and a Standardized Realistic Head Model

In this paper, distributed electroencephalographic (EEG) sources in the brain have been mapped with the objective of early diagnosis of Alzheimer's disease (AD). To this end, records from a montage of a high-density EEG from 17 early AD patients and 17 matched healthy control subjects were considered. Subjects were in eyes-closed, resting-state condition. Cortical EEG sources were modeled by the standardized low-resolution brain electromagnetic tomography (sLORETA) method. Relative logarithmic power spectral density values were obtained in the four conventional frequency bands (alpha, beta, delta, and theta) and 12 cortical regions. Results show that in the left brain hemisphere, the theta band of AD subjects shows an increase in the power, whereas the alpha band shows a decreased activity (P-value <;0.05). In the right brain hemisphere of AD subjects, a decreased activity is observed in all frequency bands. It was also noticed that the right temporal region shows a significant difference between the two groups in all frequency bands. Using a support vector machine, control and patient groups are discriminated with an accuracy of 84.4%, sensitivity 75.0%, and specificity of 93.7%.