Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels and cAMP-Dependent Modulation of Exocytosis in Cultured Rat Lactotrophs

Hormone and neurotransmitter release from vesicles is mediated by regulated exocytosis, where an aqueous channel-like structure, termed a fusion pore, is formed. It was recently shown that second messenger cAMP modulates the fusion pore, but the detailed mechanisms remain elusive. In this study, we asked whether the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are activated by cAMP, are involved in the regulation of unitary exocytic events. By using the Western blot technique, a real-time PCR, immunocytochemistry in combination with confocal microscopy, and voltage-clamp measurements of hyperpolarizing currents, we show that HCN channels are present in the plasma membrane and in the membrane of secretory vesicles of isolated rat lactotrophs. Single vesicle membrane capacitance measurements of lactotrophs, where HCN channels were either augmented by transfection or blocked with an HCN channel blocker (ZD7288), show modulated fusion pore properties. We suggest that the changes in local cation concentration, mediated through HCN channels, which are located on or near secretory vesicles, have an important role in modulating exocytosis.
Transnational governance spirals: the transformation of rule-making authority in Internet regulation and corporate financial reporting

Transnational regulation involves profound changes in the ways rules are set today. Based on two case studies on Internet governance and the regulation of corporate financial reporting, we show that transnational governance is best understood as a dynamic, non-linear process. In both fields, regulatory institutions are constantly renegotiated between public and private actors, a process which gives rise to new, hybrid, forms of authority. The hybridization of authority challenges the common distinction between public and private authority in transnational regulation. We propose to characterize the ongoing dynamics as transnational governance spirals. Our comparative analysis follows a research strategy of causal reconstruction. To that end, we identify three mechanisms serving as analytical tools to explain transnational institution building and the observed governance spirals: integration, authorization and formalization.
The Effects of Recovery Interventions on Consecutive Days of Intermittent Sprint Exercise

King, M and Duffield, R. The effects of recovery interventions on consecutive days of intermittent sprint exercise. J Strength Cond Res 23(6): 1795-1802, 2009-The purpose of this study was to compare four recovery interventions following simulated team sport, intermittent-sprint exercise on consecutive days. Ten female netball players performed four randomized sessions of a simulated netball exercise circuit on consecutive days. Each condition consisted of two identical sessions (Session 1 and 2), with the recovery intervention implemented at the completion of Session 1. Participants performed all interventions involving: passive recovery, active recovery (ACT), cold water immersion (CWI) and contrast water therapy (CTWT). No significant differences (p > 0.05) were evident between conditions for exercise performance (vertical jump, 20-m sprint, 10-m sprint, total circuit time) during Session 2. Effect size data indicated trends for an ameliorated decline in 5 × 20-m sprints and vertical jump for CTWT and CWI, respectively. CTWT demonstrated a significant reduction (p = 0.04) in lactate post-intervention compared to ACT recovery. Further, ACT recovery resulted in a significantly elevated (p < 0.01) heart rate compared to all other conditions postintervention and demonstrated significantly higher (p < 0.01) rating of perceived exertion postintervention and muscle soreness pre-exercise Session 2. It is likely that while interventions may be applicable to team sport practices, the 24-hour recovery period between exercise bouts was sufficient to allow performance to be maintained, regardless of recovery interventions.
Authoritative and authoritarian-inconsistent teachers’ preferences for teaching methods and instructional goals

Preferences for teaching methods are influenced by several factors, including instructional goals, teacher's management style, experience and education. To discover in which ways primary school teachers with different management styles vary in their preferences for students’ cognitive and social development, 128 teachers of Estonia were questioned. According to the results, authoritative and authoritarian-inconsistent teachers used different methods more frequently for gaining cognitive than social enhancement goals. However, authoritative teachers emphasised students’ social competences significantly more than authoritarian-inconsistent teachers. Greater differences between groups were revealed in case of progressive methods. Moreover, authoritative teachers demonstrated a more conscious choice of teaching methods for a wider variety of purposes.
Empirically Validating Software Metrics for Risk Prediction Based on Intelligent Methods

The software systems which are related to national projects are always very crucial. This kind of systems always involves hi-tech factors and has to spend a large amount of money, so the quality and reliability of the software deserve to be further studied. Hence, we propose to apply three classification techniques most used in data mining fields: Bayesian belief networks (BBN), nearest neighbor (NN) and decision tree (DT), to validate the usefulness of software metrics for risk prediction. Results show that comparing with metrics such as Lines of code (LOQ and Cyclomatic complexity (V(G)) which are traditionally used for risk prediction, Halstead program difficulty (D), Number of executable statements (EXEC) and Halstead program volume (V) are the more effective metrics as risk predictors. By analyzing we also found that BBN was more effective than the other two methods in risk prediction
Natural History of the Vascular Dementias: A Prospective Study of Seven Cases

Abstract: The clinical course of vascular dementia has been described as a stepwise deterioration over time. We studied the chronologic course of cognitive performance over 1-4 years in seven patients with known ischemic cerebrovascular disease whose dementia subtype was assigned according to the clinical history and the pattern of white matter lesions seen on magnetic resonance imaging (MRI). One patient had the lacunar state, three had subcortical arteriosclerotic encephalopathy and three had multiple cortical and subcortical strokes. All were being treated with an antiplatelet agent and six received antihypertensive therapy. Four of the seven vascular dementia patients improved cognitively over the first year. A fluctuating course was eventually seen in all patients. None showed stepwise deterioration of cognitive function over time. The MRI was useful in subclassifying vascular dementia patients, but the clinical course did not appear to vary as a function of the dementia subtype.
Occupational Identity on the Edge

Throughout the higher education sector in the UK, recent decades have witnessed the increasing use of fixed-term and part-time labour, to the extent that around 50 percent of academic staff are currently employed on fixed-term contracts and in excess of 90 percent of researchers are employed on fixed-term contracts. Despite the importance of their contribution to the sector as a whole, relatively little research has been undertaken on the lived experience of undertaking contract research. The objective of this article is therefore to explore the reality and complexities of contract researchers’ working lives and the occupational identities and self-images that contract researchers construct and maintain.
The first 5 years of the family clinic for HIV at Tygerberg Hospital: family demographics, survival of children and early impact of antiretroviral therapy.

BACKGROUND Family clinics address the problems of HIV-infected children and their families. The aims were to document demographics of the children and caregivers attending the Family Clinic for HIV at Tygerberg Academic Hospital (TAH) and to investigate factors affecting disease progression in children. METHODS A retrospective folder review of children and parents attending the Family Clinic at TAH between January 1997 and December 2001, a period noted for its lack of antiretroviral treatment. RESULTS Of 432 children seen for testing, 274 children, median age 16.9 months, were HIV-infected. During follow-up, 46 children died (median age 23 months) and 113 were lost to follow-up. The majority of children were malnourished. Those <2 years of age had lower weight for age Z-scores (WAZ) than older children (p<0.001). At presentation, 47 per cent were in clinical stage B and two-thirds had moderate or severe CD4+ T cell depletion. Seventeen children had received highly active antiretroviral therapy (HAART), 12 dual and 31 monotherapy. HAART was associated with improved survival compared to dual or monotherapy. Risk of death was reduced from eleven-fold for a WAZ <-4 to four-fold between -2 and -3. There was no association with immunological and clinical classification at entry and risk of mortality. Only 18 per cent of parents were evaluated in the clinic. Non-parental care was documented for 25 per cent of families. CONCLUSIONS A low WAZ is associated with poor survival in children. Nutritional status should receive more attention in HIV disease classification in children. Parent utilization of the clinic was inadequate. Even in the absence of HAART, extended survival in children is possible.
In vivo measurement of water content of the fingernail and its seasonal change

Background/aims: Recently, there has been increasing awareness regardless keeping nails in good condition. Maintenance of an optimum water level in the nail plate is very important since water content affects the nail condition. However, a simple method for in vivo measurement of water in the nail plate quantitatively has not been reported. In this study, we applied Near infrared spectroscopy (NIR)‐based prediction of water content of the cut nail plate to in vivo measurement to obtain information about the seasonal change of water in the fingernail.
Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects.

OBJECTIVES Smoking is associated with false-positive rheumatoid factor (RF). We explored the dose-response relationship of this association, using smoking history and serum cotinine and thiocyanate concentrations as measures of tobacco exposure. METHODS A total of 6947 men and women aged 30 yr or over and free of clinical arthritis were included in the Mini-Finland Health Survey carried out between 1978 and 1980. Detailed histories of smoking and RF (sensitized sheep cell agglutination test) were obtained in the basic examination. In 2000, serum cotinine and thiocyanate were determined from serum samples collected at baseline and stored at -20 degrees C. A cut-off point of 100 microg/l was used for serum cotinine and 10 micromol/l for thiocyanate to indicate active smoking. RESULTS There was a close association between smoking and strongly positive RF. After adjustment for age, sex, coffee consumption and region, the odds ratios (95% confidence intervals in brackets) in current smokers and in those who had quit smoking were 3.94 (2.04-7.61) and 2.71 (1.33-5.53), respectively, compared with those who had never smoked. Among current smokers, the intensity, duration or tertiles of pack-years of smoking were not related to RF. No relationship between serum cotinine or thiocyanate and RF positivity was observed within the subgroups of current smokers and those who had quit. Among those who reported that they had never smoked but who nevertheless had serum cotinine levels at least 100 microg/l, the adjusted odds ratio of strongly positive RF was 4.48 (1.48-13.50) compared with people who had never smoked and whose serum cotinine levels were less than 100 microg/l. CONCLUSIONS The results are not in line with the hypothesis of a dose-response relationship between smoking exposure and RF positivity.
Fetal Exposure to Antidepressants and Normal Milestone Development at 6 and 19 Months of Age

OBJECTIVE: The goal was to investigate a possible association between exposure to antidepressants in utero and developmental milestones in early childhood. METHODS: Information on pregnancy exposures and developmental milestones at 6 and 19 months was obtained from the Danish National Birth Cohort. Of the eligible pregnant women, 415 used antidepressant medication, 489 reported depression with no medical treatment, and 81 042 reported no depression and no use of psychotropic medication. RESULTS: Children with second- or third-trimester exposure to antidepressants were able to sit 15.9 days (95% confidence interval [CI]: 6.8–25.0) and to walk 28.9 days (95% CI: 15.0–42.7) later than children of women not exposed to antidepressants but still were within the normal range of development. Fewer children with second- or third-trimester exposure to antidepressants were able to sit without support at 6 months of age (odds ratio: 2.1 [95% CI: 1.23–3.60]), and fewer were able to occupy themselves at 19 months of age (odds ratio: 2.1 [95% CI: 1.09–4.02]). None of the other milestones measured showed statistically significant associations with antidepressant exposure. CONCLUSION: The results of this study suggest a permanent or reversible effect of antidepressant exposure on fetal brain development, which may depend on the timing of exposure during pregnancy.
Asian Indians and depressive symptoms: Reframing mental health help-seeking behavior

Survey results from 96 Asian Indians in the USA found that those having depressive symptoms were more likely to have experienced social, family or relationship issues. Logistic regression analysis indicated three significant predictors: 1) individuals with anxiety problems were 11.34 times more likely to have depressive symptoms; 2) each unit increase in the score for family or relationship issues increased the likelihood of depression by 3.74 times; and 3) individuals currently employed were 90.9 percent less likely to have depressive symptoms. Reframing mental health symptoms as reactions to family/social issues will help Asian Indians step forward to seek professional help.
Worker Responses to Bully Bosses

The tragic events resulting from workplace bullying and the increased legal pressure on organizations to prohibit harassment have resulted in many organizations adopting anti-bullying policies to protect their workers from bully bosses. Whether or not these initiatives are perceived by workers to be effective, however, is unknown. This paper examines how workers (both victims and non-victims) perceive their organization's willingness to eradicate bullying, how they perceive the effectiveness of anti-bullying policies, and how they respond to bully bosses. Based on a large survey sample and several in-depth interviews, results suggest that victims and non-victims differ in their perceptions and responses.
Development and the fragmented self: Longitudinal study of dissociative symptomatology in a nonclinical sample

Dissociative behaviors and their relation to both the self and self-organization were examined using the developmental psychopathology perspective in a prospective longitudinal study of high-risk children. Participants were 168 young adults (n = 79 females, n = 89 males, age = 18–19 years) considered high-risk for poor developmental outcomes at birth due to poverty. The present study investigated whether trauma, sense of self, quality of early mother–child relationship, temperament, and intelligence were related to dissociative symptomatology measured at four times across 19 years. Findings were (a) age of onset, chronicity and severity of trauma were highly correlated and predicted level of dissociation; (b) both the avoidant and disorganized patterns of attachment were strong predictors of dissociation; (c) dissociation in childhood may be a more normative response to disruption and stress, while dissociation in adolescence and young adulthood may be more indicative of psychopathology; (d) preliminary support was found for a model proposed by G. Liotti that links disorganized attachment, later trauma, and dissociation in adulthood; and (e) strong support was found for N. Waller, F. W. Putnam, and E. B. Carlson's contention that psychopathological dissociation should not be viewed as the top end of a continuum of dissociative symptomatology, but as a separate taxon that represents an extreme deviation from normal development.
Using a Qualitative Approach to Research to Build Trust between a Non-Aboriginal Researcher and Aboriginal Participants (Australia)

This article focuses on the qualitative methodologies employed in a research project developed in collaboration with Aboriginal advisors and gaining an in‐depth understanding of Aboriginal Victorian peoples’1 connection to their ancestral lands. It outlines why qualitative methodologies were used and highlights the ethical dimensions of working with Aboriginal Victorian communities. A research partnership was developed between Aboriginal Victorian communities and the non‐Aboriginal researcher and this process was emphasised because in the past Australian Indigenous people have been grossly exploited in health research. The methods of semi‐structured interviews and focus groups were used to gain a better understanding of this topic. The novel point of this article is that it provides an honest reflection of the benefits and limitations of this qualitative research process from the perspectives of a non‐Aboriginal researcher and an Aboriginal participant, when emphasis is placed on a collaborative approach. The paper outlines what a successful qualitative research project looks like in Victorian Aboriginal communities. This can be used as a blueprint not only for working with Aboriginal Victorian communities, who have been marginalised within Australian society, but may also be relevant to other culturally diverse communities throughout the world.
Association between resting heart rate, chronotropic index, and long-term outcomes in patients with heart failure receiving β-blocker therapy: data from the HF-ACTION trial.

AIMS The aim of this study was to assess the association between resting heart rate (HR), chronotropic index (CI), and clinical outcomes in optimally treated chronic heart failure (HF) patients on β-blocker therapy. METHODS AND RESULTS We performed a sub-study in 1118 patients with HF and reduced ejection fraction (EF < 35%) included in the HF-ACTION trial. Patients in sinus rhythm who received a β-blocker and who performed with maximal effort on the exercise test were included. Chronotropic index was calculated as an index of HR reserve achieved, by using the equation (220-age) for estimating maximum HR. A sensitivity analysis using an equation developed for HF patients on β-blockers was also performed. Cox proportional hazards models were fit to assess the association between CI and clinical outcomes. Median (25th, 75th percentiles) follow-up was 32 (21, 44) months. In a multivariable model including resting HR and CI as continuous variables, neither was associated with the primary outcome of all-cause mortality or hospitalization. However, each 0.1 unit decrease in CI <0.6 was associated with 17% increased risk of all-cause mortality (hazard ratio 1.17, 95% confidence interval 1.01-1.36; P = 0.036), and 13% increased risk of cardiovascular mortality or HF hospitalization (hazard ratio 1.13, 1.02-1.26; P = 0.025). Overall, 666 of 1118 (60%) patients had a CI <0.6. Chronotropic index did not retain statistical significance when dichotomized at a value of ≤ 0.62. CONCLUSION In HF patients receiving optimal medical therapy, a decrease in CI <0.6 was associated with adverse clinical outcomes. Obtaining an optimal HR response to exercise, even in patients receiving optimal β-blocker therapy, may be a therapeutic target in the HF population.
Novel Techniques for Ex Vivo Expansion of Cord Blood: Clinical Trials

Cord blood (CB) provides an excellent alternative source of hematopoietic progenitor cells (HPC) for patients lacking human leukocyte antigen-matched peripheral blood or bone marrow graft for transplantation. However, due to the limited cell dose in CB graft, it is associated with prolonged time to engraftment, risk of graft rejection, infections, and treatment-related mortality. To increase the cell dose, a variety of ex vivo expansion techniques have been developed. Results of traditional methods of CB expansion using cytokines alone were disappointing. Expanding CB cells with mesenchymal progenitor cells led to sizeable increase in graft content and improved engraftment. Other methods used HPC-differentiation blockers, such as nicotinamide analogs, copper chelators, inducing constitutive Notch signaling, or an aryl hydrocarbon receptor antagonist (StemReginin1). Many of these methods lead to substantial expansions of total nucleated cells and CD34+ cells, and significantly improved time to neutrophil or platelet engraftment in patients transplanted with the expanded products compared to the recipients of unmanipulated CBT. These studies differ not only in the expansion method but also with regards to the cytokines used, patient population, conditioning regimens, and transplantation practices, to name a few. Some of these methods employed expansion of a portion of CB unit in the setting of single CBT, while others in the setting of double CBT. Here, we review various procedures used for CB expansion and highlight some of the key differences. Novel methods of improving engraftment that aim at improving bone marrow homing potential of CB cells are not reviewed.
The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLCϵ

R-Ras, an atypical member of the Ras subfamily of small GTPases, enhances integrin-mediated adhesion and signaling through a poorly understood mechanism. Dynamic analysis of cell spreading by total internal reflection fluorescence (TIRF) microscopy demonstrated that active R-Ras lengthened the duration of initial membrane protrusion, and promoted the formation of a ruffling lamellipod, rich in branched actin structures and devoid of filopodia. By contrast, dominant-negative R-Ras enhanced filopodia formation. Moreover, RNA interference (RNAi) approaches demonstrated that endogenous R-Ras contributed to cell spreading. These observations suggest that R-Ras regulates membrane protrusions through organization of the actin cytoskeleton. Our results suggest that phospholipase Cϵ (PLCϵ) is a novel R-Ras effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion, because R-Ras was co-precipitated with PLCϵ and increased its activity. Knockdown of PLCϵ with siRNA reduced the formation of the ruffling lamellipod in R-Ras cells. Consistent with this pathway, inhibitors of PLC activity, or chelating intracellular Ca2+ abolished the ability of R-Ras to promote membrane protrusions and spreading. Overall, these data suggest that R-Ras signaling regulates the organization of the actin cytoskeleton to sustain membrane protrusion through the activity of PLCϵ.