Miracle-dz/UniFAR-FTUs huggingface dataset:
Finite-Time Analysis of Projected Langevin Monte Carlo

We analyze the projected Langevin Monte Carlo (LMC) algorithm, a close cousin of projected Stochastic Gradient Descent (SGD). We show that LMC allows to sample in polynomial time from a posterior distribution restricted to a convex body and with concave log-likelihood. This gives the first Markov chain to sample from a log-concave distribution with a first-order oracle, as the existing chains with provable guarantees (lattice walk, ball walk and hit-and-run) require a zeroth-order oracle. Our proof uses elementary concepts from stochastic calculus which could be useful more generally to understand SGD and its variants.
Association of gene BoLA DRB 3 . 2 with production traits in a dairy herd of Antioquia , Colombia Asociación del gen BoLA DRB 3 . 2 con características productivas en un hato lechero de Antioquia , Colombia

Objective. To determine the associations of BoLA DRB3.2 alleles present in Holstein and BON x Holstein cattle to production and milk quality traits in a dairy herd of Antioquia, Colombia. Materials and methods. Ninety-one cows, 66 Holstein and 25 BxH, were genotyped for the BoLA DRB3.2 gene, through PCR-RFLP technique. Furthermore, the association of the alleles of the gene BoLA DRB3.2 with milk yield (PL305), fat yield (PG305), protein yield (PP305) fat percentage (PGRA) and protein percentage (PPRO) were determined, using a general linear model. Results. Twenty-seven BoLA DRB3.2 alleles were identified; the most frequent alleles in Holstein were: BoLA DRB3.2*23, 22, and 24 with frequencies of: 0.159, 0.129, and 0.106, respectively and the most frequent alleles in BxH were: BoLA DRB3.2*23, 24 and 20 with frequencies of: 0.20, 0.140, and 0.120, respectively. Associations of BoLA DRB3.2 alleles with production and milk quality traits were also determined. In Holstein cows the BoLA DRB3.2*36 allele was associated with low PL305 (p≤0.01), high PGRA in multiparous cows (p≤0.05) and high PG305 in primiparous cows (p≤0.01). The BoLA DRB3.2*33 allele was associated with increased in the PPRO in multiparous cows (p≤0.01). In BXH cows only the BoLA DRB3*19 allele was associated with high PGRA (p≤0.05). Conclusions. The gene BoLA DRB3.2 shows high polymorphism in both groups; Holstein and BxH and some of its allelic variants were associated with production and milk quality traits.
Does Supplementation with Royal Jelly Improve Oxidative Stress and Insulin Resistance in Type 2 Diabetic Patients?

Background: Animal studies have shown antioxidant effects of Royal Jelly (RJ) and its effect on insulin resistance as the most common complication of Type 2 diabetes. This study was conducted to determine the effect of RJ intake on serum total antioxidant capacity, Malondialdehyde and insulin resistance in T2DM. Methods: In this randomized controlled trial, forty-six type 2 diabetic patients, aged 25–65 years, with BMI of 20–30 kg/m2, and HbA1c of 6–8% were included. The patients were randomly assigned to receive 1000 mg of RJ supplement or placebo, 3 times daily for 8 weeks. HOMA-IR, anthropometric measurements, fasting blood glucose, serum insulin, total antioxidant capacity and malondialdehyde level were measured. Results: In comparison with placebo, HOMA-IR decreased (P=0.015) while serum total antioxidant capacity increased significantly in RJ group (P=0.016). No significant difference was detected for serum insulin and MDA in two groups. Conclusions: RJ intake may have favorable effects on serum TAC and HOMA-IR in diabetic patients.
Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM. To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in ∼10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.
AKAP150 Is Required for Stuttering Persistent Ca2+ Sparklets and Angiotensin II–Induced Hypertension

Hypertension is a perplexing multiorgan disease involving renal primary pathology and enhanced angiotensin II vascular reactivity. Here, we report that a novel form of a local Ca2+ signaling in arterial smooth muscle is linked to the development of angiotensin II–induced hypertension. Long openings and reopenings of L-type Ca2+ channels in arterial myocytes produce stuttering persistent Ca2+ sparklets that increase Ca2+ influx and vascular tone. These stuttering persistent Ca2+ sparklets arise from the molecular interactions between the L-type Ca2+ channel and protein kinase C&agr; at only a few subsarcolemmal regions in resistance arteries. We have identified AKAP150 as the key protein, which targets protein kinase C&agr; to the L-type Ca2+ channels and thereby enables its regulatory function. Accordingly, AKAP150 knockout mice (AKAP150−/−) were found to lack persistent Ca2+ sparklets and have lower arterial wall intracellular calcium ([Ca2+]i) and decreased myogenic tone. Furthermore, AKAP150−/− mice were hypotensive and did not develop angiotensin II–induced hypertension. We conclude that local control of L-type Ca2+ channel function is regulated by AKAP150-targeted protein kinase C&agr; signaling, which controls stuttering persistent Ca2+ influx, vascular tone, and blood pressure under physiological conditions and underlies angiotensin II–dependent hypertension.
Characterization of the GlnK protein of Escherichia coli

The GlnK and PII signal transduction proteins are paralogues that play distinct roles in nitrogen regulation. Although cells lacking GlnK appear to have normal nitrogen regulation, in the absence of PII, the GlnK protein controls nitrogen assimilation by regulating the activities of the PII receptors glutamine synthetase adenylyltransferase (ATase) and the kinase/phosphatase nitrogen regulator II (NRII or NtrB), which controls transcription from nitrogen‐regulated promoters. Here, the wild‐type GlnK protein and two mutant forms of GlnK were purified, and their activities were compared with those of PII using purified components. GlnK and PII were observed to have unique properties. Both PII and GlnK were potent activators of the phosphatase activity of NRII, although PII was slightly more active. In contrast, PII was approximately 40‐fold more potent than GlnK in the activation of the adenylylation of glutamine synthetase by ATase. While both GlnK and PII were readily uridylylated by the uridylyltransferase activity of the signal‐transducing uridylyltransferase/uridylyl‐removing enzyme (UTase/UR), only PII∼UMP was effectively deuridylylated by the UR activity of the UTase/UR. Finally, there were subtle differences in the regulation of GlnK activity by the small molecule effector 2‐ketoglutarate compared with the regulation of PII activity by this effector. Altogether, these results suggest that GlnK is unlikely to play a significant role in the regulation of ATase in wild‐type cells, and that the main role of GlnK may be to contribute to the regulation of NRII and perhaps additional, unknown receptors in nitrogen‐starved cells. Also, the slow deuridylylation of GlnK∼UMP by the UTase/UR suggests that rapid interconversion of GlnK between uridylylated and unmodified forms is not necessary for GlnK function. One mutant form of GlnK, containing the alteration R47W, was observed to lack specifically the ability to activate the NRII phosphatase in vitro ; it was able to be uridylylated by the UTase/UR and to activate the adenylylation activity of ATase. Another mutant form of GlnK, containing the Y51N alteration at the site of uridylylation, was not uridylylated by the UTase/UR and was defective in the activation of both the NRII phosphatase activity and the ATase adenylylation activity.
Studies on the pathogenesis of the ophthalmopathy of Graves' disease.

ABSTRACT Ophthalmometry and determinations of serum levels of long acting thyroid stimulator globulin (LATS), pituitary thyrotropin (TSH) and antithyroglobulin (anti-TG) antibody were performed in previously untreated hyperthyroid patients before and after administration of therapeutic doses of 131I-iodide. LATS was detected in the sera of 10 of 38 patients prior to treatment, including 7 of the 9 patients presenting with ophthalmopathy. The mean exophthalmometric reading of patients who were seropositive for LATS was more than 3 mm higher than of those who were seronegative. Observations have been made on 24 patients followed for 6 months or longer after radioiodide treatment. Most patients with LATS-negative sera remained seronegative following treatment; this group showed a mean slight but clinically unimportant increase in proptosis. In 3 patients LATS was first detected in the serum several months after treatment at a time when the subjects were clinically euthyroid. In each case the appearance of LA.
Clinical diagnostic performance of the simultaneous amplification and testing methods for detection of the Mycobacterium tuberculosis complex for smear‐negative or sputum‐scarce pulmonary tuberculosis in China

Background Early detection of pulmonary tuberculosis (PTB) is a big challenge in smear negative and sputum scarce patients in China. Simultaneous amplification and testing methods for detection of the Mycobacterium tuberculosis (MTB) complex (SAT‐TB assay) is a novel molecular technique established in our hospital. This method has a high sensitivity and specificity in the lab. In this study, the clinical diagnostic performance of this method in smear‐negative or sputum‐scarce PTB suspects was investigated and evaluated. Methods Two hundred smear negative and 80 sputum‐scarce patients were recruited in this study. Samples that included sputum or bronchial washing fluid were collected and sent for both bacteria culture and SAT‐TB assay. Diagnosis for these patients was based on the comprehensive evaluation of chestX‐ ray/CT study, histology examination, lab results, and treatment response. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each diagnostic test were investigated and calculated using confirmed tuberculosis (TB) and non‐TB cases. The time required for detection of MTB was also measured for each method. Results Ninety‐two patients (33%) were diagnosed as definitive TB, 112 patients (40%) were probable PTB, and 76 (27%) were non‐TB. The sensitivity, specificity, PPV, and NPV of SAT‐TB in smear‐negative PTB suspects were 93% (95% CI, 84%‐98%), 98% (95% CI, 90%‐100%), 98% (95% CI, 91%‐100%), and 93% (95% CI, 83%‐98%). In sputum scarce PTB suspects, the sensitivity, specificity, PPV, and NPV of the SAT‐TB assay on bronchial washing fluids were 90% (95% CI, 74%‐98%), 100% (95% CI, 85%‐100%), 100% (95% CI, 88%‐100%), and 88% (95% CI, 69%‐97%). The accuracy of the SAT‐TB assay is consistent with the bacteria culture assay. The median time required for detecting MTB in the SAT‐TB assay was 0.5 day, which was much faster than bacteria culture (28 days). Conclusions The SAT‐TB assay is a fast and accurate method for the detection of MTB. It can be widely applied in the clinic and be an asset in early detection and management of PTB suspects, especially in those patients who are smear negative or sputum scarce.
A Psycho-Educational Video Used in the Emergency Department Provides Effective Treatment for Whiplash Injuries

Study Design. Randomized control trial conducted between June 2000 and September 2002. Objective. To determine whether a short psycho-educational video shown in the Emergency Department shortly after the injury would produce follow-up pain reductions and reduced medical utilization. Summary of Background Data. Chronic pain following a whiplash injury is one example of the massive medical/legal problem of chronic muscular pain. Approaches using local pain sources (trigger points) have shown promise as treatment models for this type of pain. Methods. 1) Setting: Emergency Departments (ED) and urgent care (UC) facilities. 2) Patients: 126 patients entering EDs or UCs. 3) Intervention: Patients assigned to 12-minute video or care as usual. 4) Main Outcome Measures: Short Form Musculoskelatal Function Assessment (SMFA), phone questionnaires assessing: narcotics use, ER use, UC use, surgical consultations, etc. Results and Conclusions. Patients viewing the video had dramatically lower pain ratings at a 1-month follow (6.09 [10.6] vs. 21.23 [17.4], P < 0.001) and this pattern held for the 3- and 6-month follow-up period. Similarly, for 17 of 21 items asked at follow-up, the video group showed superior outcomes (&khgr;2 ranged from 5 to 35, P < 0.05, all). For example, 4% of video patients were using narcotics at 6 month post ED visit compared with 36% of controls. The brief psycho-educational video had a profound effect on subsequent pain and medical utilization.
Strategy games: a renewed framework

Game theory is a useful framework in multi-agent system verification. In this context, an important contribution is given by modal logics for strategic ability, such as ATL*, SL, and the like, which allow to describe the interaction among players for the achievement of specific goals. However, most of the attempts carried out so far have focused on specific forms of games in which strategic-reasoning aspects are glued with agent temporal goals. In this paper, we propose a revisit of logics for strategic reasoning by following the general guidelines of game-theory, where the definition of solution concepts abstracts away the underlying cost-benefit analysis. Specifically, we introduce a game-theoretic framework consisting of three entities: the arena, shaping the rules of the game, the extension describing the property of interest of each possible play, and the schema, representing the agent roles and their interaction. In particular, to describe the latter, we use a variant of SL, by casting away its LTL temporal core. The new framework allows to gain in flexibility, modularity, and technical simplification, as well as, to grasp new features and better complexity results about logics previously studied. To give an evidence of this, by rephrasing SL in our framework, we improve known results about some of its fragments.
Reassessing intertemporal choice: human decision-making is more optimal in a foraging task than in a self-control task

Many contemporary concerns (e.g., addiction, failure to save) can be viewed as intertemporal choice problems in which the consequences of choices are realized at different times. In some laboratory paradigms used to study intertemporal choice, non-human animals demonstrate a preference for immediacy (impulsive choice) that results in failures to maximize the amount of reward received. There is evidence, however, suggesting that such non-optimal impulsive choice may be due to a mismatch between the standard presentation of options in the laboratory (e.g., a “larger-later” and a “smaller-sooner” option) and the way that options occur in natural settings (e.g., foraging). We present evidence that human impulsive choice is similarly affected: in two experiments, decisions were more optimal when options were presented in a format sharing features with the evolutionarily important problem of foraging compared to when options were presented in the standard format. These findings suggest a more nuanced view of intertemporal choice and support the adoption of ideas from foraging theory into the study of human decision making.
Effectiveness of quinine versus artemether-lumefantrine for treating uncomplicated falciparum malaria in Ugandan children: randomised trial

Objective To compare the effectiveness of oral quinine with that of artemether-lumefantrine in treating uncomplicated malaria in children. Design Randomised, open label effectiveness study. Setting Outpatient clinic of Uganda’s national referral hospital in Kampala. Participants 175 children aged 6 to 59 months with uncomplicated malaria. Interventions Participants were randomised to receive oral quinine or artemether-lumefantrine administered by care givers at home. Main outcome measures Primary outcomes were parasitological cure rates after 28 days of follow-up unadjusted and adjusted by genotyping to distinguish recrudescence from new infections. Secondary outcomes were adherence to study drug, presence of gametocytes, recovery of haemoglobin concentration from baseline at day 28, and safety profiles. Results Using survival analysis the cure rate unadjusted by genotyping was 96% for the artemether-lumefantrine group compared with 64% for the quinine group (hazard ratio 10.7, 95% confidence interval 3.3 to 35.5, P=0.001). In the quinine group 69% (18/26) of parasitological failures were due to recrudescence compared with none in the artemether-lumefantrine group. The mean adherence to artemether-lumefantrine was 94.5% compared with 85.4% to quinine (P=0.0008). Having adherence levels of 80% or more was associated with a decreased risk of treatment failure (0.44, 0.19 to 1.02, P=0.06). Adverse events did not differ between the two groups. Conclusions The effectiveness of a seven day course of quinine for the treatment of uncomplicated malaria in Ugandan children was significantly lower than that of artemether-lumefantrine. These findings question the advisability of the recommendation for quinine therapy for uncomplicated malaria in Africa. Trial registration ClinicalTrials.gov NCT00540202.
Comparative Correlation Structure of Colon Cancer Locus Specific Methylation: Characterisation of Patient Profiles and Potential Markers across 3 Array-Based Datasets

Abnormal DNA-methylation is well known to play an important role in cancer onset and development, and colon cancer is no exception to this rule. Recent years have seen the increased use of large-scale technologies, (such as methylation microarray assays or specific sequencing of methylated DNA), to determine whole genome profiles of CpG island methylation in tissue samples. Comprehensive study of methylation array data from transcriptome high-throughput platforms permits determination of gene methylation markers, important for cancer profiling. Here, three large-scale methylation datasets for colon cancer have been compared to determine locus-specific methylation agreement. These data are from the GEO database, where colon cancer and apparently healthy adjacent tissues are represented by sample sizes 125 and 29 respectively in the first dataset, 24 of each in the second and 118 of each in the third. Several data analysis techniques have been employed, including Clustering, Discriminant Principal Component Analysis, Discriminant Analysis and ROC curves, in order (i) to obtain a better insight on the locus-specific concomitant methylation structures for these diverse data and (ii) to determine a robust potential marker set for indicative screening, drawn from all data taken together. The extent of the agreement between the analysed datasets is reported. Further, potential screening methylation markers, for which methylation profiles are consistent across tissue samples and several datasets, are highlighted and discussed.
Predictors of Mild Cognitive Impairment in Early-Stage Parkinson's Disease

Aim: The aim of this study was to identify mild cognitive deficits in Parkinson's disease (PD) prior to extensive neurodegeneration and to evaluate the extent to which dopamine depletion and other disease-related predictors can explain cognitive profiles. Methods: Neuropsychological performances of 40 nondemented early-stage PD patients and 42 healthy controls were compared across on or off dopaminergic medications. Stepwise regression evaluated cognitive predictors of early-stage PD and disease-related predictors of PD cognition (levodopa dose, disease duration, Unified Parkinson's Disease Rating Scale score, sleep, quality of life, and mood) across on and off states. Results: Neuropsychological performance was lower in PD patients across cognitive domains with significant memory, naming, visuomotor, and complex attention/executive deficits, but with intact visuospatial, simple attention, and phonemic fluency functions. However, medication effects were absent except for simple attention. Regression analyses revealed age, working memory, and memory recall to be the best cognitive predictors of PD, while age, quality of life, disease duration, and anxiety predicted PD cognition in the off state. Conclusion: Nondemented early-stage PD patients presented with extensive mild cognitive deficits including prominent memory impairment. The profile was inconsistent with expected isolated frontostriatal dysfunction previously attributed to dopamine depletion and this highlights the need to further characterize extranigral sources of mild cognitive impairment in PD.
Bacterial lipopolysaccharide stimulates glucocorticoid secretion in hypophysectomized rats.

The effect of an i.p. bolus injection of 200 micrograms.kg-1 bacterial lipopolysaccharide (LPS) on the plasma concentrations of ACTH and corticosterone (B) were studied in intact and hypophysectomized/ACTH replaced (Hx) rats. Hormonal blood levels were measured by RIA, 30, 60, 120, 180 and 240 min after the injection. The stress evoked by the vehicle i.p. injection provoked significant rises in ACTH and B blood levels at 30 and 60 min in intact rats, but not in Hx animals. In intact rats, LPS enhanced (over the respective control value) ACTH plasma level at 60, 120 and 180 min, and B plasma concentration at 120, 180 and 240 min. In Hx rats, LPS did not affect ACTH blood level, but raised B plasma concentration at 60, 120 and 180 min. B response to LPS at 120 min was completely annulled, in both intact and Hx rats, by the simultaneous administration of 25 nmol.kg-1 alpha-helical-CRH and corticotropin-inhibiting peptide that are competitive inhibitors of CRH and ACTH, respectively. The hypothesis is advanced that LPS may activate hypothalamo-pituitary adrenal axis in rats, by stimulating not only the central (hypothalamo-pituitary), but also the peripheral (intra-adrenal) branch of the CRH/ACTH system.