Miracle-dz/UniFAR-FTUs huggingface dataset:
Helix capping interactions stabilize the N-terminus of the kinesin neck coiled-coil.

In an effort to understand how specific structural features within the kinesin neck, a region of the heavy chain located between the catalytic core and stalk domains, may contribute to motor processivity (an ability to remain attached to the microtubule filament), we have prepared several synthetic peptides corresponding to the neck region of human conventional kinesin and determined their secondary structure content and stability by CD spectroscopy. Our results show that the coiled-coil dimerization domain within the human kinesin neck region corresponds to residues 337 to 369 in solution, and thus is in excellent agreement with the recent X-ray crystallographic structures of rat brain kinesin. Further, we show that the first and last heptads of this region are absolutely critical for creating the high stability and association of the dimeric structure. Interestingly, addition of the 7 N-terminal neck-linker residues (330-336) to the coiled-coil domain significantly increased its stability (Delta GdnHCl midpoint of 1 M or an increase of approximately 1.5 kcal/mol), indicating that a strong structural link exists between the neck-linker and coiled-coil region. Subsequent high-resolution structural analysis of the residues located at the junction of the neck-linker and coiled-coil revealed the presence of the two helix capping motifs, the capping box (a reciprocal interaction of Thr 336 with Gln 339) and the hydrophobic staple (a hydrophobic packing interaction of Leu 335 with Trp 340). Substitution of Leu 335 and Thr 336 (the capping residues) with Gly completely eliminated the increased stability of the coiled-coil region observed in the presence of the neck-linker residues. Correspondingly, substitution of Trp 340, the first hydrophobic core d position residue of the coiled-coil, with an Ala residue resulted in a greater than expected decrease in stability and helicity of the coiled-coil structure. Subsequent analysis of the X-ray structure and substitution analysis of Lys 341 revealed that Trp 340 makes an important interchain hydrophobic interaction with Lys 341 of the opposite chain. Taken together these results reveal that a set of strong intra- and inter-chain interactions made up of the helix "capping box," "hydrophobic staple," and the newly identified "Leu-Trp-Lys sandwich" motifs stabilize the kinesin neck coiled-coil structure, thus preventing it from fraying and unfolding.
A mental health intervention for schoolchildren exposed to violence: a randomized controlled trial.

CONTEXT No randomized controlled studies have been conducted to date on the effectiveness of psychological interventions for children with symptoms of posttraumatic stress disorder (PTSD) that has resulted from personally witnessing or being personally exposed to violence. OBJECTIVE To evaluate the effectiveness of a collaboratively designed school-based intervention for reducing children's symptoms of PTSD and depression that has resulted from exposure to violence. DESIGN A randomized controlled trial conducted during the 2001-2002 academic year. SETTING AND PARTICIPANTS Sixth-grade students at 2 large middle schools in Los Angeles who reported exposure to violence and had clinical levels of symptoms of PTSD. INTERVENTION Students were randomly assigned to a 10-session standardized cognitive-behavioral therapy (the Cognitive-Behavioral Intervention for Trauma in Schools) early intervention group (n = 61) or to a wait-list delayed intervention comparison group (n = 65) conducted by trained school mental health clinicians. MAIN OUTCOME MEASURES Students were assessed before the intervention and 3 months after the intervention on measures assessing child-reported symptoms of PTSD (Child PTSD Symptom Scale; range, 0-51 points) and depression (Child Depression Inventory; range, 0-52 points), parent-reported psychosocial dysfunction (Pediatric Symptom Checklist; range, 0-70 points), and teacher-reported classroom problems using the Teacher-Child Rating Scale (acting out, shyness/anxiousness, and learning problems; range of subscales, 6-30 points). RESULTS Compared with the wait-list delayed intervention group (no intervention), after 3 months of intervention students who were randomly assigned to the early intervention group had significantly lower scores on symptoms of PTSD (8.9 vs 15.5, adjusted mean difference, - 7.0; 95% confidence interval [CI], - 10.8 to - 3.2), depression (9.4 vs 12.7, adjusted mean difference, - 3.4; 95% CI, - 6.5 to - 0.4), and psychosocial dysfunction (12.5 vs 16.5, adjusted mean difference, - 6.4; 95% CI, -10.4 to -2.3). Adjusted mean differences between the 2 groups at 3 months did not show significant differences for teacher-reported classroom problems in acting out (-1.0; 95% CI, -2.5 to 0.5), shyness/anxiousness (0.1; 95% CI, -1.5 to 1.7), and learning (-1.1, 95% CI, -2.9 to 0.8). At 6 months, after both groups had received the intervention, the differences between the 2 groups were not significantly different for symptoms of PTSD and depression; showed similar ratings for psychosocial function; and teachers did not report significant differences in classroom behaviors. CONCLUSION A standardized 10-session cognitive-behavioral group intervention can significantly decrease symptoms of PTSD and depression in students who are exposed to violence and can be effectively delivered on school campuses by trained school-based mental health clinicians.
Relapse prevention in patients with bipolar disorder: cognitive therapy outcome after 2 years.

OBJECTIVE In a previous randomized controlled study, the authors reported significant beneficial effects of cognitive therapy for relapse prevention in bipolar disorder patients up to 1 year. This study reports additional 18-month follow-up data and presents an overview of the effect of therapy over 30 months. METHOD Patients with DSM-IV bipolar I disorder (N=103) suffering from frequent relapses were randomly assigned into a cognitive therapy plus medication group or a control condition of medication only. Independent raters, who were blind to patient group status, assessed patients at 6-month intervals. RESULTS Over 30 months, the cognitive therapy group had significantly better outcome in terms of time to relapse. However, the effect of relapse prevention was mainly in the first year. The cognitive therapy group also spent 110 fewer days (95% CI=32 to 189) in bipolar episodes out of a total of 900 for the whole 30 months and 54 fewer days (95% CI=3 to 105) in bipolar episodes out of a total of 450 for the last 18 months. Multivariate analyses of variance showed that over the last 18 months, the cognitive therapy group exhibited significantly better mood ratings, social functioning, coping with bipolar prodromes, and dysfunctional goal attainment cognition. CONCLUSIONS Patients in the cognitive therapy group had significantly fewer days in bipolar episodes after the effect of medication compliance was controlled. However, the results showed that cognitive therapy had no significant effect in relapse reduction over the last 18 months of the study period. Further studies should explore the effect of booster sessions or maintenance therapy.
Chronic depressive symptoms and Framingham coronary risk in HIV-infected and HIV-uninfected women

Abstract Depression is common in people with cardiovascular diseases (CVD) and those with HIV, and is a risk factor for CVD-related mortality. However, little is known about whether HIV influences the relationship between depression and cardiovascular risk. A total of 526 HIV-infected and 132 uninfected women from the Women's Interagency HIV Study were included in an analysis of women who completed twice-yearly study visits over 9.5 years. CVD risk was calculated at baseline and approximately 9.5 years later using the Framingham Risk Score (FRS). Chronic depressive symptoms were defined as Center for Epidemiologic Studies Depression Scale scores of 16 or greater at ≥75% of study visits. Over the follow-up period, 22.8% of HIV-infected women and 15.9% of HIV-uninfected women had chronic depressive symptoms (p=0.08). Baseline FRS was similar between HIV-infected and uninfected women (M=−5.70±SE=0.30 vs. M=−6.90± SE=0.60, p=0.07) as was follow-up FRS (M=0.82±SE=0.30 vs. M=−0.44± SE=0.73, p=0.11). Among HIV-infected and HIV-uninfected women, together, follow-up FRS was higher among women with chronic depressive symptoms as compared to those without (M=1.3± SE=0.6 vs. M=−0.3± SE=0.40, p<0.01), after adjusting for baseline FRS and other covariates. HIV status did not modify the relationship between chronic depressive symptoms and FRS. Chronic depressive symptoms accelerated CVD risk scores to a similar extent in both HIV-infected and-uninfected women. This implies that the diagnosis and treatment of depression may be an important consideration in CV risk reduction in the setting of HIV-infection. The determination of factors that mediate the depression/CVD relationship merits further study.
Deliberate self-poisoning in adolescence: why does a brief family intervention work in some cases and not others?

In a randomized trial of a brief family intervention with adolescents who had deliberately poisoned themselves, we have previously reported that, within the group of patients who did not have major depression, the family intervention was significantly superior to routine care in reducing suicidal thinking. The present paper examined whether efficacy was related to changes in family functioning or other possible mediating variables. Potential mediators included family functioning, hopelessness, depression, adolescent problem-solving and compliance with treatment. The efficacy of the family intervention in reducing suicidal ideation within the non-depressed sub-group was probably not mediated by changes in these variables. The implications of this finding are discussed.
[Depression and diabetes: from epidemiology to neurobiology].

INTRODUCTION Worldwide, diabetes mellitus and depression are among the most prevalent diseases in their respective fields, metabolism and psychiatry. However, there is evidence that patients with diabetes are at increased risk of developing depression, although a bidirectional relationship might also exist. AIM To present a comprehensive review of the clinical, epidemiological, psychosocial, emotional, and neurobiological basis of the relation between diabetes and depression. DEVELOPMENT Epidemiological studies indicate that there is not only an augmented risk of developing depression in diabetic patients, but that this association increases the morbidity and mortality of these patients. While there is a considerable number of clinical studies that support this relation, little is known about the neurochemical mechanisms that would constitute its biological basis. CONCLUSION Alterations in monoamines (serotonin and noradrenaline), the increases in cortisol by the hypothalamus-pituitary-adrenal axis, and trophic agents such as the brain-derived neurotrophic factor, through glycogen synthase kinase-3, constitute some of the abnormalities documented in diabetic patients and in animal models that could explain the association between depression and diabetes. Additionally, we briefly consider the psychoemotional factors that might underlie the depression-diabetes relation. The effects (most of them deleterious) of the antidepressive therapy in glucometabolic control are also discussed.
Emerging third-sector sports organisations and navigating uncertainty in an ‘era of austerity’: a single ethnographic case study from Liverpool

ABSTRACT There have been a number of recent policies in the UK which have attempted to capitalise on the benefits that sport potentially offers for health and well-being. These are, however, set against a somewhat incongruous backdrop of reductions in opportunities to participate, resulting from the ongoing constraints on public spending associated with austerity. In response to these constraints, an increasing number of third-sector sports organisations (TSSOs) have emerged to fill some of the gaps left by the public services that local authorities are no longer able deliver. This research draws on the experiences of one of those TSSOs, Target Football, a Community Interest Company located in Princes Park, Liverpool, one of the most deprived neighbourhoods in the UK. Drawing upon 6 years of ethnographic research, and a posteriori semi-structured interviews, this paper examines the ways in which this TSSO has navigated – and continues to navigate – the contextual uncertainty arising from austerity, to sustain sports provision in an environment where opportunities have declined in recent years. Underpinned by stakeholder theory, this research examines the relationships that exist between organisations and their stakeholders, and frames these in relation to power, legitimacy and urgency. The findings provide insight into the significant obstacles that challenge the survival of TSSOs in the context of a scarcity of resources. From a more practical perspective, these findings also provide critical insight into David Cameron’s aspiration ‘to do more with less’.
Relationship between oral health and mortality in cardiovascular diseases.

BACKGROUND, AIMS The purpose of the study was to investigate the relationship between periodontal health and fatal cardiovascular diseases (CVD). METHODS The investigation was conducted on a sample of 1393 individuals in the County of Stockholm. The subjects were examined in an epidemiological study in 1970 with respect to dental health. At a follow-up in 1997, the mortality rate of the sample during the years 1970-1996 was registered as well as cause of death according to the death certificate. Stepwise logistic regression analysis was performed in order to evaluate the influence of the investigated variables on the incidence of death from CVD. RESULTS The interactional effect between plaque and oral health score (a sum of scores for number of missing teeth, apical lesions, caries lesions and marginal bone loss), adjusted for age, gender, smoking and CVD at baseline, was significantly correlated to fatal coronary events. For individuals younger than 45 years of age, the age-adjusted incidence odds ratio of death due to CVD was 2.7 (p=0.04) if subjects with mean marginal bone loss of >10% were compared with subjects with mean marginal bone loss < or =10 %. If the stratum of individuals <45 years of age is confined to smokers, the odds ratio was found to be 3.4 (p=0.03). CONCLUSION Dental health was found to be a risk indicator of death due to CVD, especially in combination with another risk factor, smoking habits.
Hierarchical Recurrent Neural Network for Story Segmentation

A broadcast news stream consists of a number of stories and each story consists of several sentences. We capture this structure using a hierarchical model based on a word-level Recurrent Neural Network (RNN) sentence modeling layer and a sentence-level bidirectional Long Short-Term Memory (LSTM) topic modeling layer. First, the word-level RNN layer extracts a vector embedding the sentence information from the given transcribed lexical tokens of each sentence. These sentence embedding vectors are fed into a bidirectional LSTM that models the sentence and topic transitions. A topic posterior for each sentence is estimated discriminatively and a Hidden Markov model (HMM) follows to decode the story sequence and identify story boundaries. Experiments on the topic detection and tracking (TDT2) task indicate that the hierarchical RNN topic modeling achieves the best story segmentation performance with a higher F1-measure compared to conventional state-of-the-art methods. We also compare variations of our model to infer the optimal structure for the story segmentation task.
Encouraging accountability: Evangelicals and American health care reform

Although scholars have thoroughly assessed American Evangelical Protestants’ beliefs about government intervention in addressing socioeconomic stratification and racial discrimination, they have paid considerably less attention to interpretations of health care reform. Especially important is that American Evangelicalism in recent years has incorporated personal accountability in such a way that makes this group distinctive when considering social responsibility toward others. Whereas earlier Evangelicals were instrumental in furthering the social gospel, American Evangelicals today prioritize matters of personal accountability ahead of social action. The cultural toolkit available to Evangelicals includes a rationale for caring for others, but an emphasis on personal accountability shapes how they evaluate government health care interventions. This paper employs qualitative methods to understand how Evangelicals link such individualism with strategies for caring for others in the context of health care. The findings suggest that Evangelicals emphasize personal accountability, especially when evaluating government programs. However, personal accountability is accompanied by a conflicting ethical responsibility to provide care to others. The priority given to personal accountability or an ethic of care, however, varies according to the situational context or social location of white Evangelicals. These findings may be helpful in framing future health policies to draw Evangelical support.
Why Do Companies Stay Private? Determinants for IPO Candidates to Consider in Poland and the Czech Republic

We surveyed sixty-five chief financial officers (CFOs) at nonpublic and nonfinancial companies in the Czech Republic and Poland that are considered candidates for an initial public offering (IPO) to document their propensity to decline to launch an IPO and maintain private ownership. First, we found that the main arguments against launching an IPO in both countries involve information disclosure and limitations on decision-making control. Surprisingly, the majority of the managers do not see the capital market as a source of cheaper and more flexible financing compared to bank loans and other sources. In terms of exogenous factors, Polish CFOs are opportunistic with regard to the timing of an IPO. They view “the window of opportunity” in terms of overall business and industry conditions as significantly more important than do their Czech counterparts. Czech CFOs rank IPO-related demands on time and costs as the main obstacle to going public. Finally, Czech CFOs agree that a lack of confidence in the capital market is their major concern more frequently than do their Polish peers.
Accurate automated identification of selected Enterobacteriaceae at four hours

The Enterobacteriaceae Biochemical Card of the AutoMicrobic system Vitek Systems, Inc., Hazelwood, Mo. ) provides completely automated identification of members of this family within an 8-h test period. Identification of 776 clinical and stock isolates to species level by the Enterobacteriaceae Biochemical Card under routine operating conditions correlated at 96% with our present 18- to 24-h methods of identification. Further, utilizing a special program, we investigated presumptive identification of certain organisms within 4-h--an interval that provides greater practical clinical usefulness on a real-time rapid basis. In a single year, 1978, 97% of 23,464 Enterobacteriaceae isolated in our diagnostic laboratory belonged to 11 species of six genera. Our results suggest that, by limiting the number of the identified Enterobacteriaceae that could be actually presumptively reported to those 11 species of six genera. Our results suggest that, by limiting the number of the identified Enterobacteriaceae that could be actually presumptively reported to those 11 species with the highest frequency of occurrence, we could have correctly identified and presumptively reported 83% of these to genus or species after only 4 h. Approximately 2% of the isolates would have been presumptively identified and reported incorrectly, whereas the identification of the remaining 15% would not have been reported before the completed 8-h incubation period.
Discovery of Non-invasive Glycan Biomarkers for Detection and Surveillance of Gastric Cancer

Purpose: Gastric cancer (GC), one of the world's top five most common cancers, is the third leading cause of cancer related death. It is urgent to identify non-invasive biomarkers for GC. The objective of our study was to find out non-invasive biomarkers for early detection and surveillance of GC based on glycomic analysis. Method: Ethyl esterification derivatization combined with MALDI-TOF MS analysis was employed for the comprehensive serum glycomic analysis in order to investigate glycan markers that would indicate the onset and progression of gastric cancer. Upon the discovery of the candidate biomarkers, those with great potential were further validated in an independent test set. Peaks were acquired by the software of MALDI-MS sample acquisition and processing and analyzed by the software of Progenesis MALDI. Results: The differences in glycosylation were found between non-cancer controls and gastric cancer samples: hybrid and multi-branched type (tri-, tetra-antennnary glycans) N-glycans were increased in GC, yet monoantennary, galactose, bisecting type and core fucose N-glycans were decreased. In training set, core fucose (AUC=0.923, 95%CI: 0.8485 to 0.9967) played an excellent diagnostic performance for the early detection of gastric cancer. The diagnostic potential of core fucose was further validated in an independent cohort (AUC=0.854, 95%CI: 0.7592 to 0.9483). Besides, several individual glycan structures reached both statistical criteria (p-values less than 0.05 and AUC scores that were at least moderately accurate) when comparing different stages of GC samples. Conclusion: We comprehensively evaluate the serum glycan changes in different stages of GC patients including peritoneal metastasis for the first time. We determined several N-glycan biomarkers, some of these have potential in distinguishing the early stage GC from healthy controls, and the others can help to monitor the progression of GC. The findings also enhance understanding of gastric cancer.
Biorhythmic influences on functional capacity of human muscle and physiological responses.

UNLABELLED Previously, this laboratory has demonstrated that exhaustive aerobic exercise performance is not subject to significant chronobiological variation between 0800 and 2000 h, but certain physiological responses to maximal aerobic effort do fluctuate significantly within that time frame. PURPOSE The purpose of the present investigation was to determine whether muscle performance, and selected physiological responses to resistance exercise, was significantly influenced by time of day effects. METHODS Ten healthy, but untrained, men (21.1+/-0.6 yr, mean +/- SE) volunteered to participate in the study. In a balanced and randomized study design, each subject performed resistance exercise protocols on an isokinetic dynamometer with maximal effort at 0800 h, 1200 h, 1600 h, and 2000 h. Selected physiological and hormonal data were recorded before and immediately following the exercise stimulus. RESULTS The data demonstrated significant chronobiological oscillation in peak torque, average power, maximal work in a single repetition, and total work per set. Interestingly, this oscillation was manifested only at the fastest velocities of limb movement utilized. Pre- and postexercise rectal temperature exhibited significant time of day fluctuation, as did postexercise blood pressure. Plasma levels of testosterone and cortisol also displayed significant biorhythmicity under both pre- and postexercise conditions. However, exercise-induced responses (pre- to postexercise differences) of those steroid hormones did not exhibit significant biorythmic variation. Although plasma concentrations of both testosterone and cortisol were highest at 0800 h, testosterone to cortisol ratios were greatest at 2000 h. CONCLUSIONS In summary, these data suggest that maximal muscle performance does vary within the segment of the day when exercise typically occurs (0800-2000 h) but that this variation is specific to speed of movement.