Miracle-dz/UniFAR-FTUs huggingface dataset:
Rheb Binding to Mammalian Target of Rapamycin (mTOR) Is Regulated by Amino Acid Sufficiency*

The removal of extracellular amino acids or leucine alone inhibits the ability of the mammalian target of rapamycin (mTOR) to signal to the raptor-dependent substrates, p70 S6 kinase and 4E-BP. This inhibition can be overcome by overexpression of the Rheb GTPase. Rheb binds directly to the amino-terminal lobe of the mTOR catalytic domain, and activates mTOR kinase in a GTP-dependent manner. Herein we show that the binding of Rheb to endogenous and recombinant mTOR is reversibly inhibited by withdrawal of all extracellular amino acids or just leucine. The effect of amino acid withdrawal is not attributable to changes in Rheb-GTP charging; amino acid withdrawal does not alter the GTP charging of recombinant Rheb. Moreover, the binding of mTOR to Rheb mutants that are unable to bind guanyl nucleotide in vivo is also inhibited by amino withdrawal. The inhibitory effect of amino acid withdrawal is exerted through an action on mTOR, at a site largely distinct from that responsible for the binding of Rheb; deletion of the larger, carboxyl-terminal lobe of the mTOR catalytic domain eliminates the inhibitory effect of amino acid withdrawal on Rheb binding, without altering Rheb binding per se. The lesser ability of the mTOR catalytic domain to bind Rheb after amino acid withdrawal does not persist after extraction and purification of the mTOR polypeptide. Amino acid withdrawl may generate an inhibitor of the Rheb-mTOR interaction that interferes with the signaling function of TOR complex 1.
Messenger ribonucleic acid expression of 16 matrix metalloproteinases in bone-implant interface tissues of loose artificial hip joints.

Matrix metalloproteinases (MMPs) have been reported to be the major factors responsible for aseptic loosening of artificial hip joints. So far, messenger ribonucleic acid (mRNA) expression patterns of seven MMPs have been reported, but that of many other MMPs which have been newly discovered or recently considered to be responsible for prosthetic loosening is still unknown. In this study, mRNA expression pattern of 16 different types of MMPs were analyzed to evaluate which MMPs were locally produced and contributed to prosthetic loosening. Synovium-like interface tissues between bone and prosthesis were collected from 18 cases of aseptic loose artificial hip joint at revision surgery. Six cases of normal synovium were used as controls. Total RNA was extracted by single-step acid guanidinium-thiocyanate-phenol-chloroform procedure. mRNA expression of MMPs was analyzed by semiquantitative reverse transcription-polymerase chain reaction. Based on local expression pattern of MMPs at the mRNA level, aseptic loose artificial hip joint was characterized by elevated expression of MMP-1, MMP-9, MMP-10, MMP-12, and MMP-13; moderate expression of MMP-2, MMP-7, MMP-8, MMP-11, membrane type (MT)1-MMP (MMP-14), MT2-MMP (MMP-15), MT3-MMP (MMP-16), MT4-MMP (MMP-17), and MMP-19; lower expression of MMP-3; and little significance of MMP-20. The MMPs detected in this study can potentially degrade almost all components of the periprosthetic extracellular matrix. Thus, many MMP type enzymes possibly contribute to prosthetic loosening and osteolysis through pathologic extracellular matrix degradation and connective tissue/bone remodeling around prostheses.
Radial network reconfiguration method in distribution system using mutation Particle Swarm Optimization

We present a new Particle Swarm Optimization (PSO) for optimal radial network reconfiguration. Network reconfiguration is a combinatorial problem. The combination of search space increases exponentially with the number of switches. Fixed loop coding structure is introduced to reduce the number of combinations. The feature of this method is to introduce mutation operation for discrete decimal problem to PSO. This method, discrete decimal PSO with mutation (DDM-PSO), is applied to a test system with 37 nodes and 63 branches. The proposed method improves the maximum arrival number at the optimal solution from 8 to 17 compared to PSO without mutation in twenty trials. This number of DDM-PSO is also more than that of GA, 10. These results show the effectiveness of our method.
Budesonide and Nasal Allergen Challenge Testing in Man

In a nasal allergen challenge test, the effect of the glucocorticosteroid, Budesonide, on the pollen allergic type 1 reaction has been investigated, Placebo and two different dosages of budesonide were administered intranasally for 1 week before the challenge was performed, The study was designed as a double‐blind cross‐over trial.
Polysomnographic sleep disturbances in nicotine, caffeine, alcohol, cocaine, opioid, and cannabis use: A focused review.

BACKGROUND AND OBJECTIVES In the United States, approximately 60 million Americans suffer from sleep disorders and about 22 million Americans report substance dependence or use disorders annually. Sleep disturbances are common consequences of substance use disorders and are likely found in primary care as well as in specialty practices. The aim of this review was to evaluate the effects of the most frequently used substances-nicotine, alcohol, opioids, cocaine, caffeine, and cannabis-have on sleep parameters measured by polysomnography (PSG) and related clinical manifestations. METHODS We used electronic databases such as PubMED and PsycINFO to search for relevant articles. We only included studies that assessed sleep disturbances using polysomnography and reviewed the effects of these substances on six clinically relevant sleep parameters: Total sleep time, sleep onset latency, rapid-eye movement, REM latency, wake after sleep onset, and slow wave sleep. RESULTS Our review indicates that these substances have significant impact on sleep and that their effects differ during intoxication, withdrawal, and chronic use. Many of the substance-induced sleep disturbances overlap with those encountered in sleep disorders, medical, and psychiatric conditions. Sleep difficulties also increase the likelihood of substance use disorder relapse, further emphasizing the need for optimizing treatment interventions in these patients. CONCLUSION AND SCIENTIFIC SIGNIFICANCE Our review highlights the importance of systematically screening for substance use in patients with sleep disturbances and highlights the need for further research to understand mechanisms underlying substances-induced sleep disturbances and on effective interventions addressing these conditions.
Pain Assessment as Intervention: A Study of Older Adults With Severe Dementia

ObjectivesThe communication impairments that characterize severe dementia make pain assessment challenging. As such, pain problems often go undetected. Our goal was to determine whether systematic pain assessment leads to improved pain management practices and decreases nursing stress in comparison with a control condition. MethodsWe adopted a 3-month comparative longitudinal design. Nursing staff regularly assessed dementia patients' pain through the use of the Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC). A second group of nurses completed an attention-control measure for a control group of patients. In addition, nursing staff regularly completed measures of work stress to investigate the effects of the workload associated with systematic pain assessment on nurse stress. ResultsRegular use of the PACSLAC improved pain management practices over time as reflected in increased usage of analgesic medications (prescribed on “as needed” basis) in comparison with the control group. As pain interventions increased, a corresponding decrease in observable pain behaviors (as reflected on the PACSLAC assessments that were completed by the nurses) was observed. In addition, nurses who used the PACSLAC reported decreased distress and burnout over time. DiscussionThis investigation provides strong support for both the importance of systematic pain assessment in long-term care and for the clinical utility of the PACSLAC in improving pain management practices and decreasing caregiver distress.
Undisplaced Intracapsular Hip Fractures: Results of Internal Fixation in 375 Patients

Three hundred seventy-five patients with an undisplaced intracapsular proximal femoral fracture were treated with internal fixation. Nonunion occurred in 24 patients (6.4%) and avascular necrosis occurred in 15 patients (4.0%). Reoperation with an arthroplasty was required in 29 patients (7.7%). The age, walking ability of the patient, and degree of impaction seen on the anteroposterior radiograph or angulation seen on the lateral radiographs were of statistical significance in predicting fracture healing complications. The results for this series of patients were compared with the results in published reports identified by a comprehensive literature search. Summation of the results indicated that the overall risk of redisplacement or nonunion of the fracture was 4.3% (95% confidence interval, 3.4%–5.3%) with internal fixation of an undisplaced intracapsular fracture. For conservative treatment, the failure rate was 19.6% (95% confidence interval, 17.2%–22.1%). The incidence of avascular necrosis with internal fixation at 1 year was 2.2% (95% confidence interval, 1.6%–2.9%) compared with 2.8% (95% confidence interval, 1.9%–4.0%) with nonoperative treatment. Internal fixation is recommended for the treatment of undisplaced intracapsular hip fractures.
Psychological, endocrine, and neural correlates of attentional bias in subclinical depression

ABSTRACT Background: Our knowledge with respect to psychological, endocrine, and neural correlates of attentional bias in individuals with high vulnerability to developing depression – the subclinically depressed, still remains limited. Design: The study used a 2 × 2 mixed design. Methods: Attentional bias toward happy and sad faces in healthy (N = 26) and subclinically depressed individuals (N = 22) was assessed via a neuroimaging dot-probe attention task. Participants also completed trait and state psychological measures and provided saliva samples for cortisol analysis. Results: The subclinical group showed attentional bias toward happy faces; past use of problem-focused coping strategies when dealing with a personally relevant stressor as well as state levels of anxiety, together, contributed to this bias. In the control group, the happy attentional bias was positively correlated with activity in the right caudate. In the subclinical group, the bias was negatively associated with the left fusiform gyrus and positively with the left inferior parietal lobule and bilateral putamen. We observed group differences in association between cortisol levels during the task and neural activity during happy attentional bias processing within the key regions involved in attention. Conclusions: The attentional bias toward happy faces may reflect an active coping attempt by the subclinical participants.
Antiandrogenic therapy for the treatment of early stage prostatic cancer

The goal of this study was to achieve clinical application of antiandrogens for the treatment of carcinoma of the prostate. Based on the results obtained from animal experiments and from a pilot clinical trial on prostatic cancer patients using various antiandrogenic compounds, chlormadinone acetate (CMA) was selected for a clinical trial in patients with carcinoma of the prostate. With nine universities and their affiliated hospitals participating, the therapeutic effect of CMA for carcinoma of the prostate was investigated nationwide. Highly satisfactory antitumor effects with CMA were observed in stage A and B patients of the primary treatment group. For stage C patients in the primary treatment group, good antitumor effects were obtained with CMA treatment. For stage D patients, however, results were poor. No serious side effects were observed in spite of the long period (as long as 6.3 years) and relatively large doses (100 mg daily) of CMA. Therefore, it was concluded that CMA can be recommended as a first choice drug for patients with carcinoma of the prostate.
WeText: Scene Text Detection under Weak Supervision

The requiring of large amounts of annotated training data has become a common constraint on various deep learning systems. In this paper, we propose a weakly supervised scene text detection method (WeText) that trains robust and accurate scene text detection models by learning from unannotated or weakly annotated data. With a "light" supervised model trained on a small fully annotated dataset, we explore semi-supervised and weakly supervised learning on a large unannotated dataset and a large weakly annotated dataset, respectively. For the unsupervised learning, the light supervised model is applied to the unannotated dataset to search for more character training samples, which are further combined with the small annotated dataset to retrain a superior character detection model. For the weakly supervised learning, the character searching is guided by high-level annotations of words/text lines that are widely available and also much easier to prepare. In addition, we design an unified scene character detector by adapting regression based deep networks, which greatly relieves the error accumulation issue that widely exists in most traditional approaches. Extensive experiments across different unannotated and weakly annotated datasets show that the scene text detection performance can be clearly boosted under both scenarios, where the weakly supervised learning can achieve the state-of-the-art performance by using only 229 fully annotated scene text images.
Effect of Modified Slow Breathing Exercise on Perceived Stress and Basal Cardiovascular Parameters

Context: Different types of breathing exercises have varied effects on cardiovascular parameters and the stress levels in an individual. Aim: The aim of this study was to assess the effect of a modified form of isolated alternate nostril, slow breathing exercise on perceived stress, and cardiovascular parameters in young, male volunteers. Settings and Design: This was a randomized control study carried out at Advanced Centre for Yoga Therapy Education and Research, Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry in 2014. Subjects and Methods: Hundred healthy male volunteers were randomized into control group, n = 50 and slow breathing group (study), n = 50. Slow breathing exercise training was given to study group for 30 min a day, 5 times/week for 12 weeks, under the supervision of certified yoga trainers. Perceived Stress Scale (PSS) using Cohen's questionnaire, anthropometric parameters such as body mass index (BMI), waist-hip ratio (WHR), and cardiovascular parameters such as heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded at baseline and after 12 weeks. The control group did not receive any intervention. Slow breathing exercise training was provided for the study group. During the study period, one volunteer opted out of the study group due to personal reasons. Results: HR, SBP, DBP, and PSS decreased significantly (P < 0.05) in the study group following 12 weeks slow breathing exercise training, while no significant change (P > 0.05) was observed in BMI and WHR. There was no significant change in the control group. Conclusion: Twelve weeks of modified slow breathing exercise reduced perceived stress and improved the cardiovascular parameters. The above results indicate that our modified slow breathing exercise is effective in reducing stress and improving the cardiovascular parameters.
International Student-Athletes in Canadian Interuniversity Sport (CIS): Perceptions, Motivations, and Experiences

This exploratory study investigated the landscape of international student-athletes participating in Canadian Interuniversity Sport (CIS), the governing body for university sport in Canada, with respect to number, sport, and gender breakdown, as well as their perceptions, motivations, and experiences. Of the over 11,000 CIS student-athletes competing in 2012–14, 5.1% were international. In addition, the sports with the highest number of international student-athletes were basketball and soccer. Semistructured interviews with 16 international student-athletes from the four regional associations determined that the majority of participants were motivated to attend a Canadian university for the opportunity to combine athletics with academics. Furthermore, the experiences of those international student-athletes interviewed were mostly positive. This study may benefit university institutions, their athletics programs, as well as the CIS by providing knowledge of the motives of international student-athletes as.
Ultrastructure of the subventricular zone in Macaca fascicularis and evidence of a mouse‐like migratory stream

Recent publications have shown that the lateral wall of the lateral ventricles in the Macaca fascicularis brain, in particular the subventricular zone (SVZ), contains neural stem cells throughout adulthood that migrate through a migratory pathway (RMS) to the olfactory bulb (OB). To date, a detailed and systematic cytoarchitectural and ultrastructural study of the monkey SVZ and RMS has not been done. We found that the organization of the SVZ was similar to that of humans, with the ependymal layer surrounding the lateral ventricles, a hypocellular GAP layer formed by astrocytic and ependymal expansions, and the astrocyte ribbon, composed of astrocytic bodies. We found no cells corresponding to the type C proliferating precursor of the rodent brain. Instead, proliferating cells, expressed as Ki‐67 immunoreactivity, were predominantly young neurons concentrated in the anterior regions, and occasional astrocytes of the ribbon. We observed displaced ependymal cells of still unknown significance. New neurons tended to organize in chain‐like structures, which were surrounded by astrocytes. This pattern was highly reminiscent of that observed in rodent RMS, but not in humans. These chains spread from the frontal SVZ along a GAP‐like layer, uniquely composed of astrocytic expansions, to the olfactory bulb (OB). The number of neuronal chains and the number of chain‐forming cells decreased gradually upon reaching the OB. The purpose of this work is to provide a reference for future studies in the field of adult neurogenesis that may lead to an understanding of the fate and functionality of newborn neurons in primates, and ultimately in humans. J. Comp. Neurol. 514:533–554, 2009. © 2009 Wiley‐Liss, Inc.
Tau Exons 2 and 10, Which Are Misregulated in Neurodegenerative Diseases, Are Partly Regulated by Silencers Which Bind a SRp30c·SRp55 Complex That Either Recruits or Antagonizes htra2β1*

Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exon 2 modulates the tau N-terminal domain, which interacts with the axonal membrane. Exon 10 codes for a microtubule binding domain, increasing the affinity of tau for microtubules. Both exons are excluded from fetal brain, but their default behavior is inclusion, suggesting that silencers are involved in their regulation. Exon 2 is significantly reduced in myotonic dystrophy type 1, whose symptoms include dementia. Mutations that affect exon 10 splicing cause frontotemporal dementia (FTDP). In this study, we investigated three regulators of exon 2 and 10 splicing: serine/arginine-rich (SR) proteins SRp55, SRp30c, and htra2β1. The first two inhibit both exons; htra2β1 inhibits exon 2 but activates exon 10. By deletion analysis, we identified splicing silencers located at the 5′ end of each exon. Furthermore, we demonstrated that SRp30c and SRp55 bind to both silencers and to each other. In exon 2, htra2β1 binds to the inhibitory heterodimer through its RS1 domain but not to exon 2, whereas in exon 10 the heterodimer may sterically interfere with htra2β1 binding to a purine-rich enhancer (defined by FTDP mutation E10-Δ5 = Δ280K) directly downstream of the silencer. Increased exon 10 inclusion in FTDP mutant ENH (N279K) may arise from abolishing SRp30c binding. Also, htra2β3, a naturally occurring variant of htra2β1, no longer inhibits exon 2 splicing but can partially rescue splicing of exon 10 in FTDP mutation E10-Δ5. This work provides interesting insights into the splicing regulation of the tau gene.
Incidence and risk factors for Dengue virus (DENV) infection in the first 2 years of life in a Brazilian prospective birth cohort

SUMMARY This study assessed the incidence and risk factors for dengue virus (DENV) infection among children in a prospective birth cohort conducted in the city of Recife, a hyperendemic dengue area in Northeast Brazil. Healthy pregnant women (n = 415) residing in Recife who agreed to have their children followed were enrolled. Children were followed during their first 24 months of age (May/2011–June/2014), before the 2015 Zika virus outbreak. DENV infection was detected by reverse-transcriptase polymerase chain reaction and/or serology (anti-DENV IgM/IgG). The incidence rates per 1000 person-years (py) and its association with risk factors by age bands (0–12, >12–30 months) were estimated through Poisson regression models. Forty-nine dengue infections were detected; none progressed to severe forms. The incidence rates were 107·6/1000py (95% CI 76·8–150·6) and 93·3/1000py (95% CI 56·1–154·4) in the first and second years of age, respectively. Male children (risk ratios (RR) = 2·33; 95% CI 1·09–4·98) and those born to DENV-naïve mothers (RR = 2·42; 95% CI 1·01–5·80) were at greater risk of infection in the first year of age. In the second year, children born to Caucasian/Asian descent skin colour mothers had a threefold higher risk of infection (RR = 3·34; 95% CI: 1·08–10·33). These data show the high exposure of children to DENV infection in our setting and highlight the role of biological factors in this population's susceptibility to infection.
An Empirical Study on Capital Structure in Indian Manufacturing Sector

The study has been divided into two parts. The first part of the article analyzes the trends of capital structure of selected sample companies. The second part analyzes empirically the impact of leverage on firm’s value of selected sample companies. A sample size of 422 listed Indian manufacturing companies on Bombay Stock Exchange (BSE) has been taken to analyze the trends and leverage effect. A period of 10 years from 2003–2004 to 2012–2013 and annual financial standalone data have been considered to analyze the trends and leverage effect. Ratio analysis and panel data approach have been applied to perform the empirical study. It has been found empirically that there is a substantial debt level in the capital structure of the companies and there is no significant relationship between firm’s value and leverage using panel data fixed effect regression approach applied on four different models. In other words, leverage has no impact on the firm’s value in Indian manufacturing industry. However, variables such as size, age, profitability and growth of the firm are positively and significantly correlated with the firm value in Indian manufacturing industry. In addition, there is a significant relationship between firm value and industry practice of the firm. Business risk has no significant relationship with firm value. Thus, the findings of the study would enhance the literature on capital structure and is relevant for the Indian manufacturing industry in taking its capital structure decisions, as it is based on the most recent data and covers the period of both pre- and post-recession of 2008–2009.