Miracle-dz/UniFAR-FTUs huggingface dataset:
High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease

BACKGROUND Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis. OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations. DESIGN Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367) SETTING University Hospitals Leuven, Leuven, Belgium. PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations. INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year. MEASUREMENTS The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death. RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042). LIMITATION This was a single-center study with a small sample size. CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations. PRIMARY FUNDING SOURCE Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).
Transjugular intrahepatic portosystemic shunt for acute variceal bleeding in patients with viral liver cirrhosis: predictors of early mortality.

OBJECTIVE The purpose of our study was to assess the predictors of early mortality after the creation of transjugular intrahepatic portosystemic shunts (TIPS) for acute variceal bleeding in patients with viral liver cirrhosis. MATERIALS AND METHODS Seventy-three patients (56 men and 17 women; mean age, 51.3 years) with viral liver cirrhosis who underwent TIPS placement for acute variceal bleeding were studied. Multiple covariates, including demographic, clinical, and biochemical parameters, were included in univariate and multivariate analyses to determine their association with early (30-day) mortality. RESULTS During the follow-up period (mean, 35 months 3 days), shunt dysfunction occurred in 33 patients (45.2%). Forty-three patients (58.9%) died, and 23 patients (31.5%) died within 30 days of TIPS. Early death was predicted independently by hyperbilirubinemia (> 3 mg/dL; p = 0.004; odds ratio, 10.6) and elevated serum creatinine level (> 1.7 mg/dL; p =0.018; odds ratio, 12.0). CONCLUSION Hyperbilirubinemia and elevated serum creatinine level are predictive of early mortality after TIPS creation for acute variceal bleeding in patients with viral liver cirrhosis.
Structure‐specific effects of lipidated oxytocin analogs on intracellular calcium levels, parental behavior, and oxytocin concentrations in the plasma and cerebrospinal fluid in mice

Oxytocin (OT) is a neuroendocrine nonapeptide that plays an important role in social memory and behavior. Nasal administration of OT has been shown to improve trust in healthy humans and social interaction in autistic subjects in some clinical trials. As a central nervous system (CNS) drug, however, OT has two unfavorable characteristics: OT is short‐acting and shows poor permeability across the blood–brain barrier, because it exists in charged form in the plasma and has short half‐life. To overcome these drawbacks, an analog with long‐lasting effects is required. We previously synthesized the analog, lipo‐oxytocin‐1 (LOT‐1), in which two palmitoyl groups are conjugated to the cysteine and tyrosine residues. In this study, we synthesized and evaluated the analogs lipo‐oxytocin‐2 (LOT‐2) and lipo‐oxytocin‐3 (LOT‐3), which feature the conjugation of one palmitoyl group at the cysteine and tyrosine residues, respectively. In human embryonic kidney‐293 cells overexpressing human OT receptors, these three LOTs demonstrated comparably weak effects on the elevation of intracellular free calcium concentrations after OT receptor activation, compared to the effects of OT. The three LOTs and OT exhibited different time‐dependent effects on recovery from impaired pup retrieval behavior in sires of CD38‐knockout mice. Sires treated with LOT‐1 showed the strongest effect, whereas others had no or little effects at 24 h after injection. These results indicated that LOTs have structure‐specific agonistic effects, and suggest that lipidation of OT might have therapeutic benefits for social impairment.
Recombinant Invasive Lactococcus lactis Carrying a DNA Vaccine Coding the Ag85A Antigen Increases INF-γ, IL-6, and TNF-α Cytokines after Intranasal Immunization

Tuberculosis (TB) remains a major threat throughout the world and in 2015 it caused the death of 1.4 million people. The Bacillus Calmette-Guérin is the only existing vaccine against this ancient disease; however, it does not provide complete protection in adults. New vaccines against TB are eminently a global priority. The use of bacteria as vehicles for delivery of vaccine plasmids is a promising vaccination strategy. In this study, we evaluated the use of, an engineered invasive Lactococcus lactis (expressing Fibronectin-Binding Protein A from Staphylococcus aureus) for the delivery of DNA plasmid to host cells, especially to the mucosal site as a new DNA vaccine against tuberculosis. One of the major antigens documented that offers protective responses against Mycobacterium tuberculosis is the Ag85A. L. lactis FnBPA+ (pValac:Ag85A) which was obtained and used for intranasal immunization of C57BL/6 mice and the immune response profile was evaluated. In this study we observed that this strain was able to produce significant increases in the amount of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6) in the stimulated spleen cell supernatants, showing a systemic T helper 1 (Th1) cell response. Antibody production (IgG and sIgA anti-Ag85A) was also significantly increased in bronchoalveolar lavage, as well as in the serum of mice. In summary, these findings open new perspectives in the area of mucosal DNA vaccine, against specific pathogens using a Lactic Acid Bacteria such as L. lactis.
Plasma Exposure to Insulin Glargine and Its Metabolites M1 and M2 After Subcutaneous Injection of Therapeutic and Supratherapeutic Doses of Glargine in Subjects With Type 1 Diabetes

OBJECTIVE In vivo, after subcutaneous injection, insulin glargine (21A-Gly-31B-Arg-32B-Arg-human insulin) is enzymatically processed into 21A-Gly-human insulin (metabolite 1 [M1]). 21A-Gly-des-30B-Thr-human insulin (metabolite 2 [M2]) is also found. In vitro, glargine exhibits slightly higher affinity, whereas M1 and M2 exhibit lower affinity for IGF-1 receptor, as well as mitogenic properties, versus human insulin. The aim of the study was to quantitate plasma concentrations of glargine, M1, and M2 after subcutaneous injection of glargine in male type 1 diabetic subjects. RESEARCH DESIGN AND METHODS Glargine, M1, and M2 were determined in blood samples obtained from 12, 11, and 11 type 1 diabetic subjects who received single subcutaneous doses of 0.3, 0.6, or 1.2 units · kg−1 glargine in a euglycemic clamp study. Glargine, M1, and M2 were extracted using immunoaffinity columns and quantified by a specific liquid chromatography-tandem mass spectrometry assay. Lower limit of quantification was 0.2 ng · mL−1 (33 pmol · L−1) per analyte. RESULTS Plasma M1 concentration increased with increasing dose; geometric mean (percent coefficient of variation) M1-area under the curve between time of dosing and 30 h after dosing (AUC0–30h) was 1,261 (66), 2,867 (35), and 4,693 (22) pmol · h · L−1 at doses of 0.3, 0.6, and 1.2 units · kg−1, respectively, and correlated with metabolic effect assessed as pharmacodynamics-AUC0–30h of the glucose infusion rate following glargine administration (r = 0.74; P < 0.01). Glargine and M2 were detectable in only one-third of subjects and at a few time points. CONCLUSIONS After subcutaneous injection of glargine in male subjects with type 1 diabetes, exposure to glargine is marginal, if any, even at supratherapeutic doses. Glargine is rapidly and nearly completely processed to M1 (21A-Gly-human insulin), which mediates the metabolic effect of injected glargine.
Automatic Programming of Robots Using Genetic Programming

The goal in automatic programming is to get a computer to perform a task by telling it what needs to be done. rather than by explicitly programming it. This paper considers the task of automatically generating a computer program to enable an autonomous mobile robot to perform the task of moving a box from the middle of an irregular shaped room to the wall. We compare the ability of the recently developed genetic programming paradigm to produce such a program to the reported ability of reinforcement learning techniques. such as Q learning. to produce such a program in the style of the subsumption architecture. The computational requirements of reinforcement learning necessitates considerable human knowledge and intervention. whereas genetic programming comes much closer to achieving the goal of getting the computer to perform the task without explicitly programming it. The solution produced by genetic programming emerges as a result of Darwinian natural selection and genetic crossover (sexual recombination) in a population of computer programs. The process is driven by a fitness measure which communicates the nature of the task to the computer and its learning paradigm.
Intrinsically Low Open Probability of α7 Nicotinic Acetylcholine Receptors Can Be Overcome by Positive Allosteric Modulation and Serum Factors Leading to the Generation of Excitotoxic Currents at Physiological Temperatures

α7 nicotinic acetylcholine receptors (nAChRs) have been a puzzle since their discovery in brain and non-neuronal tissues. Maximal transient probability of an α7 nAChR being open with rapid agonist applications is only 0.002. The concentration dependence of α7 responses measured from transfected cells and Xenopus laevis oocytes shows the same disparity in potency estimations for peak currents and net charge, despite being studied at 1000-fold different time scales. In both cases the EC50 was approximately 10-fold lower for net charge than for peak currents. The equivalence of the data obtained at such disparate time scales indicates that desensitization of α7 is nearly instantaneous. At high levels of agonist occupancy, the receptor is preferentially converted to a ligand-bound nonconducting state, which can be destabilized by the positive allosteric modulator N-(5-chloro-2,4-dimethoxyphenyl)-N′-(5-methyl-3-isoxazolyl)-urea (PNU-120596). Such currents can be sufficiently large to be cytotoxic to the α7-expressing cells. Both the potentiating effect of PNU-120596 and the associated cytotoxicity have a high temperature dependence that can be compensated for by serum factors. Therefore, despite reduced potentiation at body temperatures, use of type II positive allosteric modulators may put cells that naturally express high levels of α7 nAChRs, such as neurons in the hippocampus and hypothalamus, at risk. With a low intrinsic open probability and high propensity toward the induction of nonconducting ligand-bound states, it is likely that the well documented regulation of signal transduction pathways by α7 nAChRs in cells such as those that regulate inflammation may be independent of ion channel activation and associated with the nonconducting conformational states.
11.51: Numerical investigation of short seismic links in shear

It is well known that seismic links are usually designed to remain in elastic region during ordinary loading but withstand nonlinear deformation during seismic event having capability to dissipate seismic energy. The use of short seismic links is recommended because they are capable of dissipating seismic energy in larger quantity by shear, while the webs in these links are expected to yield in shear during large seismic events, i.e. dissipation of seismic energy by bending in links is negligible. Shear deformations are basically plane deformations of the cross section web of the link, without any significant tendency towards lateral torsional buckling. To achieve the required plastic rotation, local instabilities such as flange or web buckling should be delayed. The flange local buckling is delayed by specifying width to thickness ratio, while the web local buckling will be prevented by adding number of transverse stiffeners along the web of the link. The main purpose of the stiffeners is to preserve buckling of the seismic link web, i.e. to achieve plastification of the cross section by shear. Dissipation of energy in the stiffened link will occur sooner through inelastic shear deformations than through inelastic web buckling. The seismic links were chosen having the same cross section and the same length, but with different number of stiffeners, i.e. with three couples of stiffeners, two, one and without any stiffener respectively. A finite element modelling approach in investigating the structural behaviour of short links is presented. Both the material and geometric nonlinearities are considered in the FE modelling using the software ABAQUS and the Shear force – Displacement relationships was obtained. The FEA results are validated against the test results and the comparisons indicated that the FE analysis procedures agree well with the test results.
Distributed, Robust Auto-Scaling Policies for Power Management in Compute Intensive Server Farms

Server farms today often over-provision resources to handle peak demand, resulting in an excessive waste of power. Ideally, server farm capacity should be dynamically adjusted based on the incoming demand. However, the unpredictable and time-varying nature of customer demands makes it very difficult to efficiently scale capacity in server farms. The problem is further exacerbated by the large setup time needed to increase capacity, which can adversely impact response times as well as utilize additional power.In this paper, we present the design and implementation of a class of Distributed and Robust Auto-Scaling policies (DRAS policies), for power management in compute intensive server farms. Results indicate that the DRAS policies dynamically adjust server farm capacity without requiring any prediction of the future load, or any feedback control. Implementation results on a 21 server test-bed show that the DRAS policies provide near-optimal response time while lowering power consumption by about 30% when compared to static provisioning policies that employ a fixed number of servers.
Effectiveness of ultraviolet (UV) insect light traps for mosquitoes control in coastal areas of Samut Songkhram province, Thailand

This study aimed to investigate the effectiveness of ultraviolet (UV) insect light traps for mosquito control and to study the relationship between this effect and weather factors in coastal areas of Samut Songkhram province, Thailand. The study sites were divided into two areas, approximately 2and 4 km from the sea. The trap was placed less than one meter away from the house, where it could reach electrical plugs. The effectiveness of UV light trap was tested from September to October 2017 between 6: 00 p.m. and 6: 00 a.m., for a total of 30 days. A total of 2,605 adult mosquitoes within four species belonging to two genera were collected, including Anopheles epiroticus Linton & Harbach, Culex quinquefasciatus Say, Cx. sitiens Wiedmann and Cx. gelidus Theobald. The effectiveness of UV insect light traps in area 2 km from the sea trapped 45.96 ± 42.13 mosquitoes per night and area 4 km from the sea trapped 40.83 ± 33.61 mosquitoes per night. While, effectiveness comparison of the UV insect light traps 2 and 4 km from the sea of were shown to be statistically significantly different (p < 0.05). These results of this study are useful for planning and application of UV light traps to control mosquito populations in coastal areas of Samut Songkhram province, Thailand and other coastal areas.
Adaptive Fuzzy Control Design for Stochastic Nonlinear Switched Systems With Arbitrary Switchings and Unmodeled Dynamics

This paper deals with the problem of adaptive fuzzy output feedback control for a class of stochastic nonlinear switched systems. The controlled system in this paper possesses unmeasured states, completely unknown nonlinear system functions, unmodeled dynamics, and arbitrary switchings. A state observer which does not depend on the switching signal is constructed to tackle the unmeasured states. Fuzzy logic systems are employed to identify the completely unknown nonlinear system functions. Based on the common Lyapunov stability theory and stochastic small-gain theorem, a new robust adaptive fuzzy backstepping stabilization control strategy is developed. The stability of the closed-loop system on input-state-practically stable in probability is proved. The simulation results are given to verify the efficiency of the proposed fuzzy adaptive control scheme.
Less is More: Nyström Computational Regularization

We study Nystrom type subsampling approaches to large scale kernel methods, and prove learning bounds in the statistical learning setting, where random sampling and high probability estimates are considered. In particular, we prove that these approaches can achieve optimal learning bounds, provided the subsampling level is suitably chosen. These results suggest a simple incremental variant of Nystrom Kernel Regularized Least Squares, where the subsampling level implements a form of computational regularization, in the sense that it controls at the same time regularization and computations. Extensive experimental analysis shows that the considered approach achieves state of the art performances on benchmark large scale datasets.
Occupation Times of Jump-Diffusion Processes with Double Exponential Jumps and the Pricing of Options

In this paper, we provide Laplace transform-based analytical solutions to pricing problems of various occupation-time-related derivatives such as step options, corridor options, and quantile options under Kou's double exponential jump diffusion model. These transforms can be inverted numerically via the Euler Laplace inversion algorithm, and the numerical results illustrate that our pricing methods are accurate and efficient. The analytical solutions can be obtained primarily because we derive the closed-form Laplace transform of the joint distribution of the occupation time and the terminal value of the double exponential jump diffusion process. Beyond financial applications, the mathematical results about occupation times of a jump diffusion process are of more general interest in applied probability.
A Survey of Inverse Spectral Results

The existence of the Laplace-Beltrami operator has allowed mathematicians to carry out Fourier analysis on Riemannian manifolds [2]. We recall that the Laplace-Beltrami operator ∆ on a compact Riemannian manifold has a discrete set of eigenvalues {λj}j=1, which satisfies λj →∞ as j →∞. This is known as the spectrum of the Laplace-Beltrami operator. Inverse spectral geometry studies how much of the geometry of the manifold is determined by this spectrum. The purpose of this paper is to survey some of the results in this area and to give indications of some of the techniques used to prove them. As is customary in the literature, we will use the term the spectrum of the manifold with the same meaning as the term the spectrum of the LaplaceBeltrami operator on the manifold. We will also use the following terminology: a spectral invariant is a quantity which is determined by the spectrum of the manifold, and two Riemannian manifolds are called isospectral, if their spectra, counting multiplicities, coincide.
Determining in vivo elasticity and viscosity with dynamic Scheimpflug imaging analysis in keratoconic and healthy eyes

The paper presents a novel analysis method of corneal elasticity and viscosity based on corneal visualization Scheimpflug technology (CorVis ST) for keratoconus diagnosis. Methods for air puff force measurement and corneal imaging boundary extraction were proposed. Corneal biomechanical properties, described as tangent stiffness coefficient (STSC) and energy absorbed area (Aabsorbed), were assessed using the curves of the applied air puff force with corneal displacement to form a loading‐unloading cycle. Twenty‐five patients with keratoconus and 34 healthy control subjects, matched for intraocular pressure (IOP), were enrolled in this prospective study. The results showed that the intraclass correlation coefficients (ICC) of the STSC and Aabsorbed were 0.941 and 0.878 in Healthy group; and were 0.891 and 0.809 in Keratoconus group, respectively. Both STSC and Aabsorbed of keratoconus patients were significantly different from that of controls (both probability value P < 0.001). ROC curve analysis showed that the area under curve for STSC was 0.918 and for Aabsorbed was 0.894, which reached a good level of predictive accuracy for detecting keratoconus. Our results demonstrated that this new analysis method could be used to characterize the biomechanical properties of corneas. (a) The air puff force of CorVis ST was measured by a custom‐designed force detection system. (b) Corneal displacement was extracted from CorVis ST using a proposed imaging analysis. (c) With the utilization of the air puff force and corneal dynamic displacement, an analysis method was developed to introduce new corneal biomechanical parameters – STSC and Aabsorbed.
Rationalizability, Learning, and Equilibrium in Games with Strategic Complementarities

The authors study a rich class of noncooperative games that includes models of oligopoly competition, macroeconomic coordination failures, arms races, bank runs, technology adoption and diffusion, R&D competition, pretrial bargaining, coordination in teams, and many others. For all these games, the sets of pure strategy Nash equilibria, correlated equilibria, and rationalizable strategies have identical bounds. Also, for a class of models of dynamic adaptive choice behavior that encompasses both best-response dynamics and Bayesian learning, the players' choices lie eventually within the same bounds. These bounds are shown to vary monotonically with certain exogenous parameters. Copyright 1990 by The Econometric Society.