Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor

The ligand-binding domains of thyroid hormone (L-triiodothyronine [T3]) receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), and 9-cis RA receptors (RARs and RXRs) contain a series of heptad motifs thought to be important for dimeric interactions. Using a chimera containing amino acids 120 to 392 of chicken T3R alpha (cT3R alpha) positioned between the DNA-binding domain of the yeast GAL4 protein and the potent 90-amino-acid transactivating domain of the herpes simplex virus VP16 protein (GAL4-T3R-VP16), we provide functional evidence that binding of ligand releases T3Rs and RARs from an inhibitory cellular factor. GAL4-T3R-VP16 does not bind T3 and does not activate transcription from a GAL4 reporter when expressed alone but is able to activate transcription when coexpressed with unliganded T3R or RAR. This activation is reversed by T3 or RA, suggesting that these receptors compete with GAL4-T3R-VP16 for a cellular inhibitor and that ligand reverses this effect by dissociating T3R or RAR from the inhibitor. A chimera containing the entire ligand-binding domain of cT3R alpha (amino acids 120 to 408) linked to VP16 [GAL4-T3R(408)-VP16] is activated by unliganded receptor as well as by T3. In contrast, GAL4-T3R containing the amino acid 120 to 408 ligand-binding region without the VP16 domain is activated only by T3. The highly conserved ninth heptad, which is involved in heterodimerization, appears to participate in the receptor-inhibitor interaction, suggesting that the inhibitor is a related member of the receptor gene family. In striking contrast to T3R and RAR, RXR activates GAL4-T3R-VP16 only with its ligand, 9-cis RA, but unliganded RXR does not appear to be the inhibitor suggested by these studies. Further evidence that an orphan receptor may be the inhibitor comes from our finding that COUP-TF inhibits activation of GAL4-T3R-VP16 by unliganded T3R and the activation of GAL4-T3R by T3. These and other results suggest that an inhibitory factor suppresses transactivation by the T3Rs and RARs while these receptors are bound to DNA and that ligands act, in part, by inactivating or promoting dissociation of a receptor-inhibitor complex.
DNA vaccination

Few advances in the history of vaccination have had as quick a passage (~ 10 years) from their discovery to clinical trials and, hopefully soon, registration as DNA immunisation. A very clear picture has now emerged of the recognition of the CpG-motif rich, chimaeric bacterial DNA by dendritic cells (antigen-presenting cells [APCs]) and the subsequent activation of T lymphocytes. Both humoral and comprehensive cell-mediated responses occur in both mice and primates. No significant safety concerns have been observed following administration to several hundred human volunteers, including some children. Of special interest is the generation of strong and high avidity CD8+ cytotoxic T lymphocyte (CTL) responses in primates, following priming with chimaeric DNA and subsequent boosting with a chimaeric live viral vector, such as an attenuated poxvirus or adenovirus. The DNA may also be used as a highly potent adjuvant, inducing mainly T helper (Th)1 responses. Advantages include its potential use in the presence of antibody to the targeted infectious agent and a generally simple manufacturing process.
A Chaotic Lévy flight Approach in Bat and Firefly Algorithm for Gray level image Enhancement

Recently nature inspired metaheuristic algorithms have been applied in image enhancement field to enhance the low contrast images in a control manner. Bat algorithm (BA) and Firefly algorithm (FA) is one of the most powerful metaheuristic algorithms. In this paper these two algorithms have been implemented with the help of chaotic sequence and levy flight. One of them is FA via levy flight where step size of levy flight has been taken from chaotic sequence. In the Bat algorithm the local search has been done via levy flight with chaotic step size. Chaotic sequence shows ergodicity property which helps in better searching. These two algorithms have been applied to optimize parameters of parameterized high boost filter. Entropy, number of edge pixels of the image have been used as objective criterion for measuring goodness of image enhancement. Fitness criterion has been maximized in order to get enhanced image with better contrast. From the experimental results it is clear that BA with chaotic levy outperforms the FA via chaotic levy.
An Improved Immunohistochemical Diagnostic Technique for Canine Leptospirosis using Antileptospiral Antibodies on Renal Tissue

The purpose of this study was to compare the immunoreactivity in canine renal tissues stained with antisera specific for 3 leptospiral antigens and those processed with traditional staining methods. In addition, immunoglobulin staining was done on tissues with immunoreactivity to leptospiral antigens. Formalin-fixed renal sections from 12 dogs with chronic interstitial nephritis suspected or proven to have leptospirosis (6 dogs with silver-stained leptospires and 6 dogs in which silver-stained leptospires were not detected) were used. Antibodies consisted of a monoclonal antibody to Leptospira kirschneri serovar grippotyphosa lipopolysaccharide (LPS) and 2 polyclonal antibodies to outer membrane proteins, including OmpL1, a leptospiral porin, and LipL41, an outer membrane lipoprotein. The murine monoclonal antisera against LPS (F71C2-1) had the most abundant and consistent immunoreactivity. Immunoreactive areas were present in 6 of 6 sections positive by silver staining and included extracellular granular debris in intertubular areas, debris in macrophages, organisms in tubular lumina, and cytoplasmic granules in tubular epithelia. Antisera with specificity for the outer membrane proteins OmpL1 and LipL41 detected only intact organisms in tubular lumina. Immunoreactivity to OmpL1 (polyclonal 338) occurred in 4 of 5 sections positive by silver staining, but immunoreactivity to LipL41 (polyclonal 813) occurred in only 1 of 6 silver-positive sections. Each of the kidney sections in which leptospiral antigens were detected by immunohistochemistry also was positive by silver staining. Sections negative by silver staining were also negative by immunostaining. Although immunohistochemistry did not enhance sensitivity, amplification of signal by secondary antibody and hematoxylin counterstaining improved the ease of diagnosis and allowed better evaluation of tissue morphology than did silver staining methods. IgG was the most abundant immunoglobulin. IgG immunoreactivity occurred predominantly in plasma cells within interstitial infiltrates. Interstitial infiltrates contained abundant immunoreactivity to LPS, but immunoreactivity to OmpL1 and LipL41 was not noted.
Efficacy of Intravenous Alfacalcidol in the Treatment of Secondary Hyperparathyroidism in Patients on Hemodialysis

Background: Secondary hyperparathyroidism remains a serious problem in hemodialysis patients. The therapy of renal osteodystrophy is mainly based on lowering phosphate levels and administering vitamin D3 metabolites and calcimimetic agents. Methods: An observational, prospective, multicenter study was made to evaluate the efficacy of alfacalcidol in 185 chronic hemodialysis patients with secondary hyperparathyroidism (i-PTH >150 pg/ml). Patients with a Ca×P product >70 were excluded. Intermittent therapy with intravenous alfacalcidol was observed for 6 months. Results: The mean dose of alfacalcidol per week was 3.63 ± 1.71 µg. Patients previously treated with vitamin D3 metabolites needed higher doses of alfacalcidol (4.0 ± 1.7 vs. 3.2 ± 1.6; p = 0.01). Only 50.8% of the patients had received vitamin D3 metabolites prior to the start of the study and at baseline they had higher i-PTH levels (600.3 ± 360.5 vs. 489.9 ± 292.6, p = 0.02). i-PTH levels decreased from 546 ± 332.6 to 332.4 ± 274.5 pg/ml (p < 0.001). 60.5% of the patients had i-PTH < 300 pg/ml at the last observation. Serum calcium increased (9.4 ± 0.8 to 9.97 ± 1.0 mg/l, p < 0.001). Conclusion: Alfacalcidol reduced the levels of i-PTH and produced a slight increase in serum calcium and phosphate levels. In mild or moderate hyperparathyroidism the doses needed were lower than in severe hyperparathyroidism.
Tonapofylline: a selective adenosine-1 receptor antagonist for the treatment of heart failure

Importance of the field: The heart failure and cardiorenal syndromes are major public health hazards, affecting one in five persons during their lifetime. Alternatives to traditional loop-diuretics, including vasopressin and adenosine A1 receptor antagonists are now in development. Areas covered in this review: The pathophysiologic rationale for the use of tonapofylline, an intravenous and oral adenosine A1 receptor antagonist, in patients with heart failure and/or the cardiorenal syndrome are reviewed. A comprehensive review of published literature describing its medicinal chemistry, pharmacokinetics, efficacy, safety and tolerability are provided. We searched the Medline/PubMed and Embase databases for the terms ‘BG9928’, ‘tonapofylline’, ‘Adentri’, ‘adenosine’, ‘heart failure’, ‘renal failure’ and ‘cardiorenal syndrome’ from 1 January 1992 to the present. References from pertinent manuscripts were also reviewed for additional relevant content. What the reader will gain: The reader will better appreciate the potential role of tonapofylline in patients with heart failure and/or the cardiorenal syndrome. Additionally, the reader will gain an understanding of the current state of drug development and the rationale for the need for continued research. Take home message: Tonapofylline promotes natriuresis and diuresis, and may preserve glomerular filtration rate in patients with heart failure. Additionally, pilot data indicate that tonapofylline may be renoprotective in the setting of concomitant treatment with a loop-diuretic. Adverse effects were generally mild.
Neuropsychiatric problems in Parkinson's disease: Comparisons between self and caregiver report

Introduction: This study examined the level of agreement between caregiver and Parkinson's disease (PD) patient reports of neuropsychiatric problems. Method: Forty-three patients and 43 informants who knew the patient well (caregivers) participated in the study. Caregivers rated patients’ behaviour, as well as their own stress, using the Neuropsychiatric Inventory (NPI). Information from patients was obtained using commonly used scales (Beck Depression Inventory, Apathy Scale, Unified Parkinson's Disease Rating Scale and the Hamilton Anxiety Depression Scale). Both the patients and the caregivers also completed the Frontal Systems Behavior Scale, which assesses behaviours associated with apathy, disinhibition and executive dysfunction. Results: The level of agreement between these self and caregiver reports was low, with only 45.8% agreement for depression, 45.0% for apathy, 28.6% for hallucinations, 26.9% for sleep problems and 6.7% for anxiety. Conclusions: Given this low level of agreement between self and other report, these two methods of assessment cannot be considered interchangeable.
Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms.

OBJECTIVE To determine the effects of medical cannabinoids on pain, spasticity, and nausea and vomiting, and to identify adverse events. DATA SOURCES MEDLINE, the Cochrane Database, and the references of included studies were searched. STUDY SELECTION Systematic reviews with 2 or more randomized controlled trials (RCTs) that focused on medical cannabinoids for pain, spasticity, or nausea and vomiting were included. For adverse events, any meta-analysis for the conditions listed or of adverse events of cannabinoids was included. SYNTHESIS From 1085 articles, 31 relevant systematic reviews were identified including 23 for pain, 5 for spasticity, 6 for nausea and vomiting, and 12 for adverse events. Meta-analysis of 15 RCTs found more patients taking cannabinoids attained at least a 30% pain reduction: risk ratio (RR) of 1.37 (95% CI 1.14 to 1.64), number needed to treat (NNT) of 11. Sensitivity analysis found study size and duration affected findings (subgroup differences, P ≤ .03), with larger and longer RCTs finding no benefit. Meta-analysis of 4 RCTs found a positive global impression of change in spasticity (RR = 1.45, 95% CI 1.08 to 1.95, NNT = 7). Other results were not consistently statistically significant, but when positive, a 30% or more improvement in spasticity had an NNT of 10. Meta-analysis of 7 RCTs for control of nausea and vomiting after chemotherapy found an RR of 3.60 (95% CI 2.55 to 5.09) with an NNT of 3. Adverse effects caused more patients to stop treatment (number needed to harm [NNH] of 8 to 22). Individual adverse events were very common, including dizziness (NNH = 5), sedation (NNH = 5), confusion (NNH = 15), and dissociation (NNH = 20). "Feeling high" was reported in 35% to 70% of users. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) evaluation reduced evidence ratings of benefit to low or very low. CONCLUSION There is reasonable evidence that cannabinoids improve nausea and vomiting after chemotherapy. They might improve spasticity (primarily in multiple sclerosis). There is some uncertainty about whether cannabinoids improve pain, but if they do, it is neuropathic pain and the benefit is likely small. Adverse effects are very common, meaning benefits would need to be considerable to warrant trials of therapy.
ENERGY COST INDEX AS AN ESTIMATE OF ENERGY EXPENDITURE OF CEREBRAL‐PALSIED CHILDREN DURING ASSISTED AMBULATION

The energy expenditure of cerebral‐palsied children ambulating with bilateral quad canes and wheeled walkers was estimated, using average heart rate and speed of walking. An energy cost index (average number of heart rates per unit distance walked) was derived to allow for varying speeds among patients. Children were then categorized into those who had a lower energy cost index when using quad canes and those who had a lower index when using walkers. This made it possible to offer treatment recommendations based on objective data.
Block differential space-time modulation with decision-feedback detection in Rayleigh fading

Time variation on fading channels hinders accurate channel estimation in differential space-time modulation and deteriorates the performance. Decision-feedback differential detection is considered for block differential space-time modulation and compared with conventional differential space-time modulation. It is observed that the proposed scheme does not suffer effective fading bandwidth expansion as does the conventional scheme. An improved effective signal-to-noise ratio approach is proposed for analyzing the performance of the system. Theoretical analysis and simulation show the improved performance of the proposed scheme over the conventional scheme
Parents' and health-care providers' perspectives on side- effects of childhood cancer treatment in Indonesia.

BACKGROUND Efficacy of childhood cancer treatment in low-income countries may be impacted by parents' and health-care providers' perspectives on chemotherapy-related side-effects. This study explores prevalence and severity of side-effects in childhood cancer, and compares health beliefs about side-effects between parents and health-care providers, and between nurses and doctors in Indonesia. MATERIALS AND METHODS Semi-structured questionnaires were filled in by 40 parents and 207 health-care providers in an academic hospital. RESULTS Parents exporessed a desire to receive more information about side-effects (98%) and worried about this aspect of treatment (90%), although side-effects were less severe than expected (66%). The most frequent was behavior alteration (98%) and the most severe was hair loss. Only 26% of parents consulted doctors about side-effects. More parents, compared to health-care providers, believed that medicines work better when side-effects are more severe (p<0.001), and accepted severe side-effects (p=0.021). More health-care providers, compared to parents, believed that chemotherapy can be stopped or the dosage altered when there are side-effects (p=0.011). More nurses, compared to doctors, stated that side-effects were unbearable (p=0.004) and made them doubt efficacy of treatment (p<0.001). CONCLUSIONS Behavior alteration is the most frequent and hair loss the most severe side-effect. Apparent discrepancies in health beliefs about side-effects exist between parents and health-care providers. A sustainable parental education program about side-effects is recommended. Health-care providers need to update and improve their knowledge and communication skills in order to give appropriate information. Such measures may improve outcome of childhood cancer treatment in low-income countries, where adherence to therapy is a major issue.
IPSO-based Parameter Identification of Semiconductor Devices

An efficient and simple method of parameter identification for semiconductor devices is presented in this paper. The method is based on improved particle swarm optimization (IPSO), which can overcome some deficiencies of standard PSO. A typical semiconductor device, Schottky-barrier diode (SBD), has been used as an example for demonstration. The performance of the IPSO was compared with the standard PSO and the genetic algorithm (GA) that is commonly applied to solve parameter identification problems of semiconductor devices. The comparative results indicate that the IPSO method can obtain optimum solutions more easily than others.
Stress and symptoms of depression among medical students at the University of Copenhagen

Objective: This article aims to assess the levels of stress and symptoms of depression among Danish medical students, as well as explore the effect of social support on psychological distress. The results are based on numbers from the follow-up study ‘From Student to Graduate’ (j.nr 2006-41-6876). Materials and methods: Two dimensions of stress, frequency and perception, were measured on a scale from 0–6. Odds ratios and significance of associations between the various exposure variables and the outcome measure, symptoms of depression, were calculated using multiple logistic regression and Wald tests. Results: 30.5% of the students reported depressive symptoms. Stress frequency measured a mean of 2.26 (SD = 1.35). The mean for stress perception was 2.85 (SD = 1.30). Women reported higher levels of stress and depression compared to male medical students, but the differences were not significant (p > 0.05). Only the dimensions of stress and coping alone were significantly associated with reporting symptoms of depression (p < 0.001). Students coping alone had a two times higher odds ratio for reporting depressive symptoms. Conclusions: Nearly one third of the participants reported feeling depressed. Stress levels were moderate, but significantly associated with symptoms of depression. The interaction between the stress dimensions and the outcome measure illustrates the importance of stress appraisal. Coping alone with psychological problems was significantly associated with symptoms of depression.
Preventing Illegitimate Extrasynaptic Acetylcholine Receptor Clustering Requires the RSU-1 Protein

Diffuse extrasynaptic neurotransmitter receptors constitute an abundant pool of receptors that can be recruited to modulate synaptic strength. Whether the diffuse distribution of receptors in extrasynaptic membranes is a default state or is actively controlled remains essentially unknown. Here we show that RSU-1 (Ras Suppressor-1) is required for the proper distribution of extrasynaptic acetylcholine receptors (AChRs) in Caenorhabditis elegans muscle cells. RSU-1 is an evolutionary conserved cytoplasmic protein that contains multiple leucine-rich repeats (LRRs) and interacts with integrin-dependent adhesion complexes. In rsu-1 mutants, neuromuscular junctions differentiate as in the wild type, but AChRs assemble into ectopic clusters that progressively enlarge during development. As a consequence, the synaptic content of AChRs is reduced. Our study provides the first evidence that an RSU-1-dependent active mechanism maintains extrasynaptic receptors dispersed and indirectly regulates synapse maturation. SIGNIFICANCE STATEMENT Using Caenorhabditis elegans neuromuscular junction as a model synapse, we uncovered a novel mechanism that regulates the distribution of acetylcholine receptors (AChRs). In an unbiased visual screen for mutants with abnormal AChR distribution, we isolated the ras suppressor 1 (rsu-1) mutant based on the presence of large extrasynaptic clusters. We show that disrupting rsu-1 causes spontaneous clustering of extrasynaptic receptors that are normally dispersed, independently of synaptic cues. These clusters outcompete synaptic domains and cause a decrease of synaptic receptor content. These results indicate that the diffuse state of extrasynaptic receptors is not a default state that is simply explained by the lack of synaptic cues but necessitates additional proteins to prevent spontaneous clustering, a concept that is relevant for developmental and pathological situations.
The Disparity between Long-Term and Short-Term Forecasted Earnings Growth

We find the disparity between long-term and short-term analyst forecasted earnings growth is a robust predictor of future returns and long-term analyst forecast errors. After adjusting for industry characteristics, stocks whose long-term earnings growth forecasts are far above or far below their implied short-term forecasts for earnings growth have negative and positive subsequent risk-adjusted returns along with downward and upward revisions in long-term forecasted earnings growth, respectively. Additional results indicate that investor inattention toward firm-level changes in long-term earnings growth is responsible for these risk-adjusted returns.
Effects of season and regulated photoperiod on the reproductive performance of sows

Reproductive performance of experimental commercial Dalland sows (n = 87) maintained under a constant photoperiod (10 h light and 14 h darkness) and control sows (n = 187) maintained under natural daylight length (10.4 h light in winter and 13.4 h light in summer) were compared. In early summer 4.1% of experimental sows returned to oestrus compared to 20.8% of the control sows. In late summer 9.1% of experimental sows returned to oestrus compared to 21.9% of the control sows. Reduced photoperiod improved the farrowing rate of experimental sows in the early summer breeding compared to the control group (95.4% and 81.3%, respectively). With winter breeding there was a small proportion of sows that returned to service in both groups (7.9% and 8.9%) while the farrowing rate was high in both groups (93.9% and 91.0% in the experimental and control groups, respectively). Litter sizes derived from early summer services were 11.4 and 11.6 for the experimental and control groups, respectively, while winter services led to litter sizes of 11.6 and 12.4 whereas in late summer services, regulated photoperiod had improved the litter size of the experimental group (12.3) compared to the control group (11.2).