Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein−DNA binding in the absence of specific base-pair recognition

Significance Understanding molecular mechanisms of how regulatory proteins, called transcription factors (TFs), recognize their specific binding sites encoded into genomic DNA represents one of the central, long-standing problems of molecular biophysics. Strikingly, our experiments demonstrate that DNA context characterized by certain repeat symmetries surrounding specific TF binding sites significantly influences binding specificity. We expect that our results will significantly impact the understanding of molecular, biophysical principles of transcriptional regulation, and significantly improve our ability to predict how variations in DNA sequences, i.e., mutations or polymorphisms, and protein concentrations influence gene expression programs in living cells. Until now, it has been reasonably assumed that specific base-pair recognition is the only mechanism controlling the specificity of transcription factor (TF)−DNA binding. Contrary to this assumption, here we show that nonspecific DNA sequences possessing certain repeat symmetries, when present outside of specific TF binding sites (TFBSs), statistically control TF−DNA binding preferences. We used high-throughput protein−DNA binding assays to measure the binding levels and free energies of binding for several human TFs to tens of thousands of short DNA sequences with varying repeat symmetries. Based on statistical mechanics modeling, we identify a new protein−DNA binding mechanism induced by DNA sequence symmetry in the absence of specific base-pair recognition, and experimentally demonstrate that this mechanism indeed governs protein−DNA binding preferences.
Listening to Young Peopleís Voices: Youth Sports Leadersí Advice on Facilitating Participation in Sport

This article reports on a study that accepts the proposal that we listento the voices of young people in relation to sport and physical recreation.The study sought the advice of young sports leaders on what can be done to facilitate young people’s involvement in sport. The study used group interviews (Nominal Group Technique) with over 600 14–18-year-olds toelicit responses to a single question, ‘What can be done to help young people participate in sport? ’ This article focuses on young people’s views on issues to do with climate and conditions. We argue that, while their advice offers support for some current initiatives in youth sport, it also provides new insights and challenges and suggests a reordering of existing priorities for youth sport and leisure provision.
Review: The genetics of Alzheimer's disease; putting flesh on the bones

For two decades the search for genes involved in Alzheimer's disease brought little reward; it was not until the advent of genome‐wide association studies (GWAS) that genetic associations started to be revealed. Since 2009 increasingly large GWAS have revealed 20 loci, which in itself is a substantial increase in our understanding, but perhaps the more important feature is that these studies have highlighted novel pathways that are potentially involved in the disease process. This commentary assembles our latest knowledge while acknowledging that the casual functional variants, and undoubtedly, other genes are still yet to be discovered. This is the challenge that remains and the promise of next‐generation sequencing is anticipated as there are a number of large initiatives which themselves should start to yield information before long.
Anāsakti and Health: A Study of Non-attachment

This study examined the health consequences of an indigenous concept "Anāsakti" which means non-attachment. The scale measuring anāsakti was based on the characteristics of a man of steady wisdom "the sthitaprajña", described in the Bhagvad Gītā. It was hypothesised that those higb on anāsakti would experience less distress and exhibit fewer symptoms of strain when faced with stressful life events. Results showèd tbat anāsakt subjects were less distressed and exhibited fewer symptoms of ill health. Anāsakti was also found to be the most significant predictor of strain symptoms.
Exact result for the effective conductivity of a continuum percolation model.

A random two-dimensional checkerboard of squares of conductivities 1 and \ensuremath{\delta} in proportions p and 1-p is considered. Classical duality implies that the effective conductivity obeys ${\mathrm{\ensuremath{\sigma}}}^{\mathrm{*}}$= \ensuremath{\surd}\ensuremath{\delta} at p=1/2. It is rigorously found here that to leading order as \ensuremath{\delta}\ensuremath{\rightarrow}0, this exact result holds for all p in the interval (1-${\mathit{p}}_{\mathit{c}}$,${\mathit{p}}_{\mathit{c}}$), where ${\mathit{p}}_{\mathit{c}}$\ensuremath{\approxeq}0.59 is the site percolation probability, not just at p=1/2. In particular, ${\mathrm{\ensuremath{\sigma}}}^{\mathrm{*}}$(p,\ensuremath{\delta})= \ensuremath{\surd}\ensuremath{\delta} +O(\ensuremath{\delta}), as \ensuremath{\delta}\ensuremath{\rightarrow}0, which is argued to hold for complex \ensuremath{\delta} as well. The analysis is based on the identification of a ``symmetric'' backbone, which is statistically invariant under interchange of the components for any p\ensuremath{\in}(1-${\mathit{p}}_{\mathit{c}}$,${\mathit{p}}_{\mathit{c}}$), like the entire checkerboard at p=1/2. This backbone is defined in terms of ``choke points'' for the current, which have been observed in an experiment.
To appear in Statistica Sinica) Nonparametric Conditional Inference for Regression Coefficients with Application to Configural Polysampling

We consider inference procedures, conditional on an observed ancillary statistic, for regression coefficients under a linear regression setup where the un- known error distribution is specified nonparametrically. We establish conditional asymptotic normality of the regression coefficient estimators under regularity con- ditions, and formally justify the approach of plugging in kernel-type density estima- tors in conditional inference procedures. Simulation results show that the approach yields accurate conditional coverage probabilities when used for constructing confi- dence intervals. The plug-in approach can be applied in conjunction with configural polysampling to derive robust conditional estimators adaptive to a confrontation of contrasting scenarios. We demonstrate this by investigating the conditional mean squared error of location estimators under various confrontations in a simulation study, which successfully extends configural polysampling to a nonparametric con- text.
Comparative sequence and structure analysis reveal features of cold adaptation of an enzyme in the thermolysin family

Knowledge about the structural features underlying cold adaptation is important for designing enzymes of different industrial relevance. Vibriolysin from Antarctic bacterium strain 643 (VAB) is at present the only enzyme of the thermolysin family from an organism that thrive in extremely cold climate. In this study comparative sequence‐structure analysis and molecular dynamics (MD) simulations were used to reveal the molecular features of cold adaptation of VAB. Amino acid sequence analysis of 44 thermolysin enzymes showed that VAB compared to the other enzymes has: (1) fewer arginines, (2) a lower Arg/(Lys + Arg) ratio, (3) a lower fraction of large aliphatic side chains, expressed by the (Ile + Leu)/(Ile + Leu + Val) ratio, (4) more methionines, (5) more serines, and (6) more of the thermolabile amino acid asparagine. A model of the catalytic domain of VAB was constructed based on homology with pseudolysin. MD simulations for 3 ns of VAB, pseudolysin, and thermolysin supported the assumption that cold‐adapted enzymes have a more flexible three‐dimensional (3D) structure than their thermophilic and mesophilic counterparts, especially in some loop regions. The structural analysis indicated that VAB has fewer intramolecular cation–π electron interactions and fewer hydrogen bonds than its mesophilic (pseudolysin) and thermophilic (thermolysin) counterparts. Lysine is the dominating cationic amino acids involved in salt bridges in VAB, while arginine is dominating in thermolysin and pseudolysin. VAB has a greater volume of inaccessible cavities than pseudolysin and thermolysin. The electrostatic potentials on the surface of the catalytic domain were also more negative for VAB than for thermolysin and pseudolysin. Thus, the MD simulations, the structural patterns, and the amino acid composition of VAB relative to other enzymes of the thermolysin family suggest that VAB possesses the biophysical properties generally following adaptation to cold climate. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Self-stabilizing unidirectional network algorithms by power-supply

Power supply, a surprisingly simple and new general paradigm for the development of self-stabilizing algorithms in different models, is introduced. The paradigm is exemplified by developing simple and efficient self-stabilizing algorithms for leader election and either breadth-first search or depth-first search spanning-tree constructions, in strongly connected unidirectional and bidirectional dynamic networks (synchronous and asynchronous). The different algorithms stabilize in O(n) time in both synchronous and asynchronous networks without assuming any knowledge of the network topology or size, where n is the total number of nodes. Following the leader election algorithms, we present a generic self-stabilizing spanning tree and/or leader election algorithm that produces a whole spectrum of new and efficient algorithms for these problems. Two variations that produce either a rooted depth-first search tree or a rooted breadth-first search tree are presented.
Adaptive Analysis of On-line Algorithms

On-line algorithms are usually analyzed using competitive analysis, in which the performance of on-line algorithm on a sequence is normalized by the performance of the optimal on-line algorithm on that sequence. In this paper we introduce adaptive/cooperative analysis as an alternative general framework for the analysis of on-line algorithms. This model gives promising results when applied to two well known on-line problems, paging and list update. The idea is to normalize the performance of an on-line algorithm by a measure other than the performance of the on-line optimal algorithm OPT. We show that in many instances the perform of OPT on a sequence is a coarse approximation of the difficulty or complexity of a given input. Using a finer, more natural measure we can separate paging and list update algorithms which were otherwise undistinguishable under the classical model. This createas a performance hierarchy of algorithms which better reflects the intuitive relative strengths between them. Lastly, we show that, surprisingly, certain randomized algorithms which are superior to MTF in the classical model are not so in the adaptive case. This confirms that the ability of the on-line adaptive algorithm to ignore pathological worst cases can lead to algorithms that are more efficient in practice.
Narrative performance and parental scaffolding of shy and nonshy children

ABSTRACT This study examined differences in performance between 20 shy and 20 matched nonshy children on a narrative task and in the way parents scaffolded their narrative performance when reading the wordless book Frog, Where Are You, by Mercer Mayer. Consistent with previous research, results demonstrated that shy children spoke less than their nonshy peers and volunteered less story content. Parents, however, did not differ in how they scaffolded their children's speech turns, nor in the amount of semantic information they provided. Thus, these communicative differences were not accounted for by differential adult scaffolding. Implications for encouraging more verbal behavior from shy children and for the design of wordless storybooks are discussed.
A Brief Measure of Social Support: Practical and Theoretical Implications

Two studies leading to the development of a short form of the Social Support Questionnaire (SSQ) are reported. In Study 1 three items selected for high correlations with the total score (SSQ3) were administered to 182 university students together with several personality measures. SSQ3 had acceptable test-retest reliability and correlations with personality variables similar to those of the SSQ. Internal reliability was marginal although acceptable for an instrument with so few items. Study 2 employed three sets of data in developing a six-item instrument (SSQ6). The SSQ6 had high internal reliability and correlated highly with the SSQ and similarly to it with personality variables. The research findings accompanying the development of the short form social support measure suggest that perceived social support in adults may be a reflection of early attachment experience.
Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation1

Tumors have evolved multiple mechanisms to evade immune destruction. One of these is expression of T cell inhibitory ligands such as programmed death-ligand 1 (PD-L1; B7-H1). In this study, we show that PD-L1 is highly expressed on mesothelioma tumor cells and within the tumor stroma. However, PD-L1 blockade only marginally affected tumor growth and was associated with the emergence of activated programmed death-1+ ICOS+ CD4 T cells in tumor-draining lymph nodes, whereas few activated CD8 T cells were present. Full activation of antitumor CD8 T cells, characterized as programmed death-1+ ICOS+ Ki-67+ and displaying CTL activity, was only observed when CD4 T cells were depleted, suggesting that a population of suppressive CD4 T cells exists. ICOS+ foxp3+ regulatory T cells were found to be regulated through PD-L1, identifying one potentially suppressive CD4 T cell population. Thus, PD-L1 blockade activates antitumor CD8 T cell most potently in the absence of CD4 T cells. These findings have implications for the development of PD-L1-based therapies.
Burnout as a process: commentary on Cordes, Dougherty and Blum

An eager and idealistic young woman begins her new job as a social worker, determined to make a signi®cant dierence in the lives of her less fortunate clients. A cynical and depressed veteran social worker merely goes through the motions, convinced that her clients are beyond help and are simply getting what they deserve. It is the same woman, 3 years later. This stereotypic example illustrates why burnout is so insidious and therefore important to study: it corrupts the noble impulse to help others. Unfortunately, most research focuses on burnout as a state, a more or less stable outcome of a limited and static set of predictors, rather than as a process, a dynamic phenomenon that emerges from the interactions of many variables. The neglect of process is surprising because, as the Cordes, Dougherty, and Blum article details, there are at least two directly competing models of burnout:
The National Literacy Strategy: missing a crucial link? A comparative study of the National Literacy Strategy and Success for All

This article contrasts two major attempts at educational reform with regard to literacy. Starting with a brief background to the introduction of the National Literacy Strategy, together with an analysis of research into effective literacy teaching, it presents qualitative research carried out in the form of a comparative study of the National Literacy Strategy and Success for All. This small-scale study of four schools confirmed the hypothesis that the underpinning pedagogy needs to be explicitly understood for such a large-scale initiative to be effective.
Examining Laughter Functionality in Jury Deliberations

Despite a presumption that laughter and a death penalty decision seem incompatible, transcript data of jury deliberations from both the guilt-or-innocence and penalty phases of the State of Ohio v. Mark Ducic trial demonstrate that jurors do laugh. Working from the disparate literature on laughter, we problematized laughter from a group communication perspective and analyzed its functionality in jury interaction. The authors identified and analyzed 51 laughter sequences across 414 transcript pages. Three categories of laughter functions (i.e., relational, processual, and informational) were identified; these categories were further detailed by 6, 10, and 10 subfunctions, respectively. Based on these findings, the authors revised their definition of laughter to incorporate its multifunctionality as vocalic and public emotional displays that (a) can be read as positive, negative, or ambiguous and (b) question, control, and regulate relationships, procedures, and information in the group. That laughter can be read in so many ways suggests that one role of laughter may be to create ambiguity to allow the group a chance to figure out what to do next.
Latino Fathers and Their Children

This article examines Latino fathers and their influence on child well-being in light of recent demographic, cultural, and social shifts. Through use of a heuristic model of father involvement, this study found great heterogeneity in the way Latino fathers are engaged with their offspring and at least suggests an emerging hybrid that blends traditional with more modern views of parenting. Findings imply that a father's personal characteristics and experiences (such as cultural values and beliefs, immigration experience, motivation to parent, and financial, social, and human capital) and quality of his relationships (coparenting and couple) are important correlates of involvement with his children. There appear to be multiple mechanisms linking aspects of paternal involvement to child outcomes, including the quality of the mother–father and parent–child relationship and the father's own interactions (language input, supportiveness) with the child. These findings are considered in the context of methodological, conceptual, and measurement challenges that future studies should address.
International Conference on Intercultural Education “ Education and Health : From a transcultural perspective ” Improving the Graphic Creativity Levels of Latin American High School Students Currently Living in Spain by Means of a Mindfulness Program

In this study we will analyze the impact of a mindfulness program upon the graphic creativity levels of a group of Latin American teenagers currently living in Spain. To do so, we analyzed an experimental group of Latin American teenagers who took part in the mindfulness training program, and a control group who did not take part in it. The levels of graphic creativity of both groups were evaluated by means of the Torrance Thinking Test of the Graphic Battery. The statistical study showed how the levels of fluency and originality have significantly increased if compared with the levels of the control group. The results of this research prove the usefulness of mindfulness techniques as useful and effective strategies for graphic creativity improvement, and may become an empiric support so as to incorporate and use them within the educational environment. © 2014 The Authors. Published by Elsevier Ltd. Selection and peer-review under responsibility of Encarnación Soriano, Christine Sleeter and María Antonia Casanova.
Daily low-dose cisplatin plus concurrent high-dose thoracic irradiation in locally advanced unresectable non-small-cell lung cancer: results of a phase II Southwest Oncology Group study.

PURPOSE This single-arm phase II trial was designed to evaluate the efficacy and toxicity of continuous-course, high-dose thoracic irradiation (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of cisplatin. PATIENTS AND METHODS Sixty-five patients from 21 participating institutions were entered onto the study between April 1989 and May 1991. Protocol therapy consisted of daily intravenous (i.v.) cisplatin (5 mg/m2) plus concurrent continuous-course RT (61 Gy over 6 1/2 weeks) both delivered Monday through Friday each week. After a 3- to 4-week rest period, this was followed by three 28-day cycles of cisplatin at 100 mg/m2 or subsequently 50 mg/m2 administered i.v. on days 1 and 8 of each cycle. RESULTS Sixty-four patients were eligible; the majority had unresectable stage IIIa (36%) or IIIb (55%) NSCLC. The remaining 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is demonstrated by the fact that only five patients (8%) were unable to complete daily cisplatin and RT because of toxicity. Esophagitis (16%), leukopenia (14%), nausea (8%), and vomiting (6%) were the most common severe (grade 3) toxicities. There was only one life-threatening toxicity (grade 4 nausea) and no treatment-related deaths. The objective response rate was 39%, and six patients (9%) achieved a radiographic complete response (CR). The median survival duration for all patients was 14 months, and the 1- and 2-year actuarial survival rates were 56% and 24%, respectively. For stage IIIa patients, the median survival duration and 2-year survival rate were 17 months and 38%, as compared with 10 months and 14% for stage IIIb patients, respectively. CONCLUSION Daily low-dose cisplatin plus concurrent high-dose continuous-course RT is a well-tolerated out-patient regimen. The survival results are encouraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum analogs with RT.
Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

Background Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury. Methods and Results Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference −0.28 [−0.47, −0.09]). Conclusion There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin.