Miracle-dz/UniFAR-FTUs huggingface dataset:
Envelope glycoproteins of human immunodeficiency virus type 1: profound influences on immune functions.

Infection by human immunodeficiency virus type 1 (HIV-1) leads to progressive destruction of the CD4+ T-cell subset, resulting in immune deficiency and AIDS. The specific binding of the viral external envelope glycoprotein of HIV-1, gp120, to the CD4 molecules initiates viral entry. In the past few years, several studies have indicated that the interaction of HIV-1 envelope glycoprotein with cells and molecules of the immune system leads to pleiotropic biological effects on immune functions, which include effects on differentiation of CD34+ lymphoid progenitor cells and thymocytes, aberrant activation and cytokine secretion patterns of mature T cells, induction of apoptosis, B-cell hyperactivity, inhibition of T-cell dependent B-cell differentiation, modulation of macrophage functions, interactions with components of complement, and effects on neuronal cells. The amino acid sequence homologies of the envelope glycoproteins with several cellular proteins have suggested that molecular mimicry may play a role in the pathogenesis of the disease. This review summarizes work done by several investigators demonstrating the profound biological effects of envelope glycoproteins of HIV-1 on immune system cells. Extensive studies have also been done on interactions of the viral envelope proteins with components of the immune system which may be important for eliciting a "protective immune response. " Understanding the influences of HIV-1 envelope glycoproteins on the immune system may provide valuable insights into HIV-1 disease pathogenesis and carries implications for the trials of HIV-1 envelope protein vaccines and immunotherapeutics.
Pharmacoeconomics of opioid therapy for chronic non-malignant pain

Chronic non-malignant pain (CNMP) is widely prevalent and associated with significant costs. Costs related to chronic pain include medical services and medications, treatment of medication-related toxicity and work absenteeism. The use of non-narcotic analgesics is associated with inadequate pain-relief for many patients, as well as significant and costly organ toxicity. When used appropriately and judiciously, opioid medications can be a useful addition to the treatment plan for patients with CNMP. Opioids can provide long-term, safe and cost-effective pain relief.
National and State Treatment Need and Capacity for Opioid Agonist Medication-Assisted Treatment.

OBJECTIVES We estimated national and state trends in opioid agonist medication-assisted treatment (OA-MAT) need and capacity to identify gaps and inform policy decisions. METHODS We generated national and state rates of past-year opioid abuse or dependence, maximum potential buprenorphine treatment capacity, number of patients receiving methadone from opioid treatment programs (OTPs), and the percentage of OTPs operating at 80% capacity or more using Substance Abuse and Mental Health Services Administration data. RESULTS Nationally, in 2012, the rate of opioid abuse or dependence was 891.8 per 100 000 people aged 12 years or older compared with national rates of maximum potential buprenorphine treatment capacity and patients receiving methadone in OTPs of, respectively, 420.3 and 119.9. Among states and the District of Columbia, 96% had opioid abuse or dependence rates higher than their buprenorphine treatment capacity rates; 37% had a gap of at least 5 per 1000 people. Thirty-eight states (77.6%) reported at least 75% of their OTPs were operating at 80% capacity or more. CONCLUSIONS Significant gaps between treatment need and capacity exist at the state and national levels. Strategies to increase the number of OA-MAT providers are needed.
Eosinophil cationic protein enhances cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells by stimulating the FGF receptor signaling pathway

We investigated the functional role of eosinophil cationic protein (ECP) in regulating cardiomyogenesis using mouse P19CL6 embryonic carcinoma cells. ECP was confirmed to accelerate the cardiomyocyte differentiation of P19CL6 cells by enhancing the rate and area size of beating of cardiomyocyte and by facilitating the expression of cardiomyocyte-specific genes, such as GATA4 and α-MHC. Since cardiomyocyte differentiation in vivo is considered to follow mesoderm induction, the induction of Brachyury, a marker of mesoderm, was assessed. Brachyury expression was found to be enhanced after the addition of ECP. This enhancement was due to the stimulation of extracellular signal-regulated kinase (ERK)1/2 phosphorylation by ECP. In this context, treatment with SU5402, an inhibitor of fibroblast growth factor (FGF) receptor 1, suppressed Brachyury expression, phosphorylation of ERK1/2, and cardiomyocyte differentiation induced by ECP. We concluded that ECP might induce mesoderm differentiation through FGF signaling pathway and enhance subsequent cardiomyocyte differentiation in concert with dimethyl sulfoxide in P19CL6 cells. ECP may be a novel factor for cardiomyocyte differentiation, which should be very useful to prepare adequate numbers of cardiomyocytes for therapeutic cell transplantation.
Relating Cerebral Ischemia and Hypoxia to Insult Intensity

Abstract: The contributions of five variables believed to influence the brain's metabolism of O2 during hypoxia [duration, PaO2, ΔCMRO2 (the difference between normal and experimental oxygen uptake), O2 availability (blood O2 content · CBF), and O2 deficit (ΔCMRO2· duration)] were assessed by stepwise and multiple linear regression. Levels of brain tissue carbohydrates (lactate, glucose, and glycogen) and energy metabolites [ATP, AMP, and creatine phosphate (CrP)] were significantly influenced by O2 deficit during hypoxia, as was final CMRO2. After 60 min of reoxygenation, levels of tissue lactate, glucose, ATP, and AMP were related statistically to the O2 deficit during hypoxia; however, CMRO2 changes were always associated more significantly with O2 availability during hypoxia. Creatine (Cr) and CrP levels in the brain following reoxygenation were correlated more to ΔCMRO2 during hypoxia. Changes in some brain carbohydrate (lactate and glucose), energy metabolite (ATP and AMP) levels, and [H+]i induced by complete ischemia were also influenced by O2 deficit. After 60 min of postischemic reoxygenation, brain carbohydrate (lactate, glucose, and glycogen) and energy metabolite (ATP, AMP, CrP, and Cr) correlated with O2 deficit during ischemia. We conclude that “O2 deficit” is an excellent gauge of insult intensity which is related to observed changes in nearly two‐thirds of the brain metabolites we studied during and following hypoxia and ischemia.
Assembly of the Major Light-harvesting Chlorophyll-a/b Complex

The major light-harvesting chlorophyll-a/b complex in most higher plants contains three carotenoids, lutein, neoxanthin, and violaxanthin. How these pigments are assembled into the complex during its biogenesis is largely unknown. Here we show that neoxanthin but not lutein can dissociate from the fully assembled complex. Its equilibrium binding constant in a detergent system (0.1% n-dodecyl-β-d-maltoside) was determined to be ≥ 106 m–1. Neoxanthin insertion into light-harvesting chlorophyll-a/b complex prefolded from overexpressed apoprotein (Lhcb1*2 from Pisum sativum) in the presence of chlorophylls a, b, and lutein as the sole carotenoid is kinetically controlled by an activation energy barrier of ∼120 kJ mol–1. This is the first thermodynamic and kinetic description of a binding equilibrium between a non-covalently bound pigment of the photosynthetic apparatus and its protein complex. Dissociation of neoxanthin from the major light-harvesting chlorophyll-a/b complex upon temperature increase is discussed in terms of providing a readily available substrate pool for synthesizing abscisic acid as part of a heat and drought stress response.
Propylthiouracil-induced immune-mediated disease in the cat.

An immune-mediated disease was produced in 9 of 17 (53%) normal healthy cats by daily p.o. administration of 150 mg of 6-propylthiouracil (PTU). This disease syndrome is characterized by lethargy, weight loss, lymphadenopathy, hemolytic anemia, a positive direct antiglobulin test (DAT) and antinuclear antibodies (ANA). The duration of drug administration before the development of a positive DAT and/or ANA ranged from 3 to 8 weeks (Mean +/- S.E.M. = 4.5 +/- 0.6), whereas the duration before the onset of clinical signs ranged from 4 to 8 weeks (6.1 +/- 0.6 weeks). On cessation of PTU administration, clinical signs resolved in all cats within 2 weeks, and the DAT and test for ANA were negative within 1 to 4 weeks (1.9 +/- 0.4 weeks). During nine PTU-rechallenge periods in four cats, both the mean time to develop a positive DAT and ANA (2.5 +/- 0.8 weeks) and the mean time to develop overt clinical signs (2.6 +/- 0.7 weeks) were shorter than similar mean times in the initial PTU treatment period (P less than .01). During nine episodes of PTU-induced disease in seven cats, PTU administration was discontinued and replaced with 150 mg of 6-propyluracil (PU), a nonsulfur analog of PTU. Resolution of both clinical and serologic signs of disease occurred in seven of the nine disease episodes within 1 to 3 weeks (2.1 +/- 0.4 weeks). In the two cats whose disease did not resolve on PU, one was sacrificed after 1 week of PU administration, without clinical or serologic resolution, because of the severity of the PTU-induced disease. (ABSTRACT TRUNCATED AT 250 WORDS)
Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis.

OBJECTIVE To verify the hypothesis that in rheumatoid arthritis (RA), tumor necrosis factor alpha (TNFalpha) plays a critical role in regulating leukocyte trafficking and chemokine levels. METHODS Ten patients with longstanding RA received a single 10 mg/kg infusion of anti-TNFalpha monoclonal antibody (cA2). The articular localization of autologous granulocytes, separated in vitro and labeled with 111In, was studied by analysis of gamma-camera images both before and 2 weeks after treatment. At the same sequential time points, synovial biopsy samples were assessed for infiltrating CD3+ T cells, CD22+ B cells, and CD68+ macrophages. Synovial tissue expression of the chemokines interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, Groalpha, and RANTES was also determined. Serum IL-8 and MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS Anti-TNFalpha therapy in RA significantly reduced 111In-labeled granulocyte migration into affected joints. There was a simultaneous and significant reduction in the numbers of infiltrating synovial CD3+ T cells, CD22+ B cells, and CD68+ macrophages and in the expression of IL-8 and MCP-1, with a trend toward a reduction in serum concentrations of these chemokines. CONCLUSION TNFalpha blockade reduces synovial expression of the chemokines IL-8 and MCP-1 and diminishes inflammatory cell migration into RA joints.
Combination of Duplex Ultrasound-Guided Manual Declotting and Percutaneous Transluminal Angioplasty in Thrombosed Native Dialysis Fistulas

Background. To investigate the safety, feasibility, efficacy, and long-term patency rate of manual declotting under duplex ultrasound (US) guidance followed by percutaneous transluminal angioplasty (PTA) in thrombosed native arteriovenous fistulas (AVFs). Methods. Of 87 consecutive thrombosed AVFs evaluated by duplex US, 22 patients with 25 recently thrombotic events in 22 AVFs were suitable for manual declotting. PTA was performed following successful declotting, and long-term patency was assessed. Results. The procedure success rate of manual declotting was 80% (20 of 25), and a residual stenosis of 74 ± 9% was identified by duplex US after declotting. PTA reduced the diameter stenosis to 25 ± 6% and increased the lumen diameter from 1.33 ± 0.85 mm to 4.62 ± 0.98 mm. Neither embolic nor bleeding complications were noted during the procedure. The average procedure time and the fluoroscopy time were 28.4 ± 9.9 and 7.2 ± 4.1 minutes, respectively. Primary patency rates at 1, 2, and 3 years were 47%, 35%, and 28%; assisted primary patency rates at 1, 2, and 3 years were 71%, 63%, and 63%; and secondary patency rates at 1, 2, and 3 years were 76%, 71%, and 63%, respectively, during a maximum follow-up period of 42 months. Conclusion. The combination of duplex US-guided manual declotting and angioplasty of underlying stenosis is a safe and feasible method to treat recently thrombosed native AVFs in selected patients. It simplifies the interventional procedure, reduces cost and radiation exposure time, and extends life span of dialysis fistula with acceptable long-term patency rate.
Type VI secretion is a major virulence determinant in Burkholderia mallei

Burkholderia mallei is a host‐adapted pathogen and a category B biothreat agent. Although the B. mallei VirAG two‐component regulatory system is required for virulence in hamsters, the virulence genes it regulates are unknown. Here we show with expression profiling that overexpression of virAG resulted in transcriptional activation of ∼60 genes, including some involved in capsule production, actin‐based intracellular motility, and type VI secretion (T6S). The 15 genes encoding the major sugar component of the homopolymeric capsule were up‐expressed > 2.5‐fold, but capsule was still produced in the absence of virAG. Actin tail formation required virAG as well as bimB, bimC and bimE, three previously uncharacterized genes that were activated four‐ to 15‐fold when VirAG was overproduced. Surprisingly, actin polymerization was found to be dispensable for virulence in hamsters. In contrast, genes encoding a T6S system were up‐expressed as much as 30‐fold and mutations in this T6S gene cluster resulted in strains that were avirulent in hamsters. SDS‐PAGE and mass spectrometry demonstrated that BMAA0742 was secreted by the T6S system when virAG was overexpressed. Purified His‐tagged BMAA0742 was recognized by glanders antiserum from a horse, a human and mice, indicating that this Hcp‐family protein is produced in vivo during infection.
Reduction of mutual coupling between closely-packed antenna elements with split ring resonator (SRR)

This paper presents a new method to reduce mutual coupling between two closely-packed planar inverted F antennas (PIFAs) with split ring resonator (SRR). A SRR structure has been inserted between the two elements. The design model has been analyzed and optimized with the commercial software package HFSS 11.0, thus a mutual coupling reduction of more than 6 dB was achieved at resonant frequency. The method is also verified by fabricated model and measurement has been carried out by using E8363B Vector Network Analyzer of Agilent. The experimental results agree very well with simulated results.
A high-precision chronological model for the decorated Upper Paleolithic cave of Chauvet-Pont d’Arc, Ardèche, France

Significance We compiled a set of more than 250 radiocarbon dates related to the rock art, human activities, and bone remains in the Chauvet-Pont d'Arc Cave (Ardèche, France) and derive a modeled absolute chronology of the human and cave bear occupations of this site, presented here in calendar years. It provides an insightful framework for the successive events that occurred in the cave during the Paleolithic period. Radiocarbon dates for the ancient drawings in the Chauvet-Pont d’Arc Cave revealed ages much older than expected. These early ages and nature of this Paleolithic art make this United Nations Educational, Scientific and Cultural Organization (UNESCO) site indisputably unique. A large, multidisciplinary dating program has recently mapped the anthropological evolution associated with the cave. More than 350 dates (by 14C, U-Th, TL and 36Cl) were obtained over the last 15 y. They include 259 radiocarbon dates, mainly related to the rock art and human activity in the cave. We present here more than 80 previously unpublished dates. All of the dates were integrated into a high-precision Bayesian model based on archaeological evidence to securely reconstruct the complete history of the Chauvet-Pont d’Arc Cave on an absolute timescale. It shows that there were two distinct periods of human activity in the cave, one from 37 to 33,500 y ago, and the other from 31 to 28,000 y ago. Cave bears also took refuge in the cave until 33,000 y ago.
Role of neurotrophins in mouse neuronal development

During vertebrate development, naturally occurring neuronal cell death is regulated by target‐derived peptide factors, called neurotrophins. A recent series of papers describe the phenotypes of germline‐targeted mutant mice deficient in neurotrophins and their receptors. Histological analysis of these mice for the first time has provided knowledge about the specific neuron populations that are dependent on neurotrophin action for development. Mice deficient for nerve growth factor (NGF) and its high‐affinity receptor, encoded by the trkA proto‐oncogene, suffer from complete loss of sympathetic neurons and sensory neurons responsive to temperature and pain. Mice deficient for brain‐derived neurotrophic factor (BDNF) and its receptor, encoded by the trkB gene, display loss of sensory neurons responsive to tactile stimuli. In addition, trkB mutant mice experience loss of motor neurons indicating a possible specific function of the second TrkB ligand, neurotrophin‐4 (NT‐4), in motor neuron development. Mice deficient for neurotrophin‐3 (NT‐3) and its receptor, encoded by the trkC gene, show abnormal movements caused by the loss of sensory proprioceptive neurons. — Klein, R. Role of neurotrophins in mouse neuronal development. FASEB J. 8: 738‐744; 1994.
L'élévation du pH des vins : causes, risques oenologiques, impacts de la mise en oeuvre de moyens d'acidification

La perception empirique des changements d'acidite des raisins ces dernieres annees dans le Sud de la France conduit souvent a conclure que l'evolution des pH a la hausse est un risque avere. L'analyse de donnees objectives montre que cette hausse des pH est la consequence indirecte de la recherche de la pleine maturite, garante de la meilleure expression des terroirs qui amene a vendanger des raisins riches en sucres et pauvres en acide malique. Les principales consequences, audela de l'intensite et de la stabilite de la couleur, sont essentiellement d'ordre microbiologique: les vins sont plus favorables au developpement de Brettanomyces, de Pediocoques et de Lactobacilles, tous susceptibles de masquer les qualites originales des vins. Nos resultats microbiologiques (effet du pH sur la fermentation malo-lactique, resistance au SO 2 actif de Brettanomyces), organoleptiques ou analytiques confirment l'interet de l'utilisation de membranes bipolaires pour reguler le pH apres FML.
Distributed Replica-Exchange Simulations on Production Environments Using SAGA and Migol

There exists a class of scientific applications for which utilizing distributed resources is critical for reducing the time-to-solution. In this paper, we discuss a specific class of applications - Replica-Exchange simulations - where the orchestration of many distributed jobs in a dynamic and inherently unreliable distributed environment is essential for a successful completion. We describe the design, development and deployment of a unique framework for constructing fault-tolerant distributed simulations. The framework consists of two primary components - SAGA and Migol. SAGA is a high-level programmatic abstraction layer that provides a standardised interface for the primary distributed functionality required for application development. We present details of a newly developed functionality in SAGA - the Checkpoint and Recovery (CPR) API. Migol is an adaptive middleware, which supports the fault-tolerance of distributed applications by providing the capability to recover applications from checkpoint files transparently. In addition to describing the integration of SAGA-CPR with the Migol infrastructure, we outline our experiences with running a large scale, general-purpose Replica-Exchange application in a production distributed environment.
Twin studies on senescence.

1. By means of the twin family method and up to the end of 1947, a representative sample of 1,602 twin index cases over 6o years of age was collected from both the general and institutionalized populations of the state of New York, in order to study the biological, social, and psychiatric problems of senescence under experiment-like, but mankind-specific conditions. The study was organized in such a way that complete life histories can be obtained for the purpose of analyzing the differences observed between one-egg and two-egg twin groups with regard to length of life, senile manifestations, and causes of death. 2. The random sampling of the series of aged twins included in this preliminary analysis is indicated not only by the sex distribution of the index cases (697 males to 905 females), but also by the obtained ratio of monozygotic to dizygotic pairs (237 to 548). 3. Many basic elements in the physical and psychological similarities of one-egg twin partners have a tendency to persist throughout life .
Conformational analysis of the anti-HIV Nikavir prodrug: comparisons with AZT and Thymidine, and establishment of structure–activity relationships/tendencies in other 6′-derivatives

A comprehensive theoretical conformational analysis of the anti-HIV Nikavir prodrug was carried out; this prodrug has noticeable advantage over the approved drug AZT. The whole conformational parameters (χ, α, β, γ, δ, ϕ, P and νmax) were analysed as well as the NBO natural atomic charges. The calculations were carried out by means of DFT/B3LYP and ab initio MP2 methods with full relaxation of all geometrical parameters. The search located at least 67 stable structures, 4 of which were within a 1 kcal/mol electronic energy range of the global minimum. By MP2 it corresponds to the calculated values of the exocyclic torsional angles χ = –108.0°, β = 14.5°, γ = 76.7° and ε = 71.5°. The results obtained are in accordance to those found in related anti-HIV nucleoside analogues. Comparisons of the conformers with those determined in the common anti-HIV drug AZT were carried out. A detailed analysis of the lowest vibrations (<200 cm−1) in the best conformer of Nikavir was carried out. The most stable hydrated cluster of this conformer with 20 explicit water molecules was determined. Calculations in five of its 6′-derivatives were performed to identify structural trends that might correlate with the anti-HIV activity of these compounds. Ten structure–activity relationships/tendencies were established that can help for the design of new drugs. Several recommendations for this design were expressed.
Automated Cellient™ cytoblocks: better, stronger, faster?

Cytoblocks (CBs), or cell blocks, provide additional morphological detail and a platform for immunocytochemistry (ICC) in cytopathology. The Cellient™ system produces CBs in 45 minutes using methanol fixation, compared with traditional CBs, which require overnight formalin fixation. This study compares Cellient and traditional CB methods in terms of cellularity, morphology and immunoreactivity, evaluates the potential to add formalin fixation to the Cellient method for ICC studies and determines the optimal sectioning depth for maximal cellularity in Cellient CBs.