Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of T Cell Ig Mucin-3 Signaling on Central Nervous System Autoimmune Disease Is Determined by the Effector Function of the Pathogenic T Cells

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS mediated by self-reactive, myelin-specific T cells. Both CD4+ and CD8+ T cells play important roles in the pathogenesis of MS. MS is studied using experimental autoimmune encephalomyelitis (EAE), an animal model mediated by myelin-specific T cells. T cell Ig mucin-3 (Tim-3) is a cell surface receptor expressed on CD4+ IFN-γ–secreting Th1 cells, and triggering Tim-3 signaling ameliorated EAE by inducing death in pathogenic Th1 cells in vivo. This suggested that enhancing Tim-3 signaling might be beneficial in patients with MS. However, Tim-3 is also expressed on activated CD8+ T cells, microglia, and dendritic cells, and the combined effect of manipulating Tim-3 signaling on these cell types during CNS autoimmunity is unknown. Furthermore, CD4+ IL-17–secreting Th17 cells also play a role in MS, but do not express high levels of Tim-3. We investigated Tim-3 signaling in EAE models that include myelin-specific Th17, Th1, and CD8+ T cells. We found that preventing Tim-3 signaling in CD4+ T cells altered the inflammatory pattern in the CNS due to differential effects on Th1 versus Th17 cells. In contrast, preventing Tim-3 signaling during CD8+ T cell–mediated EAE exacerbated disease. We also analyzed the importance of Tim-3 signaling in EAE in innate immune cells. Tim-3 signaling in dendritic cells and microglia did not affect the manifestation of EAE in these models. These results indicate that the therapeutic efficacy of targeting Tim-3 in EAE is dependent on the nature of the effector T cells contributing to the disease.
Vibrio parahaemolyticus and Vibrio vulnificus Recovered from Oysters during an Oyster Relay Study

ABSTRACT Vibrio parahaemolyticus and Vibrio vulnificus are naturally occurring estuarine bacteria and are the leading causes of seafood-associated infections and mortality in the United States. Though multiple-antibiotic-resistant V. parahaemolyticus and V. vulnificus strains have been reported, resistance patterns in vibrios are not as well documented as those of other foodborne bacterial pathogens. Salinity relaying (SR) is a postharvest processing (PHP) treatment to reduce the abundances of these pathogens in shellfish harvested during the warmer months. The purpose of this study was to evaluate the antimicrobial susceptibility (AMS), pathogenicity, and genetic profiles of V. parahaemolyticus and V. vulnificus recovered from oysters during an oyster relay study. Isolates (V. parahaemolyticus [n = 296] and V. vulnificus [n = 94]) were recovered from oysters before and during the 21-day relaying study to detect virulence genes (tdh and trh) and genes correlated with virulence (vcgC) using multiplex quantitative PCR (qPCR). AMS to 20 different antibiotics was investigated using microbroth dilution, and pulsed-field gel electrophoresis (PFGE) was used to study the genetic profiles of the isolates. Twenty percent of V. vulnificus isolates were vcgC+, while 1 and 2% of V. parahaemolyticus were tdh+ and trh+, respectively. More than 77% of the V. vulnificus isolates and 30% of the V. parahaemolyticus isolates were resistant to at least one antimicrobial. Forty-eight percent of V. vulnificus and 8% of V. parahaemolyticus isolates were resistant to two or more antimicrobials. All isolates demonstrated a high genetic diversity, even among those isolated from the same site and having a similar AMS profile. No significant effects of the relaying process on AMS, virulence genes, or PFGE profiles of V. vulnificus and V. parahaemolyticus were observed. IMPORTANCE Analysis of the antibiotic resistance profiles of V. vulnificus and V. parahaemolyticus isolated from oysters during this study indicated that more than 48% of V. vulnificus isolates were resistant to two or more antimicrobials, including those recommended by the CDC for treating Vibrio infections. Also, the V. parahaemolyticus isolates showed high MICs for some of the Vibrio infection treatment antibiotics. Monitoring of AMS profiles of this bacterium is important to ensure optimal treatment of infections and improve food safety. Our study showed no significant differences in the AMS profiles of V. vulnificus (P = 0.26) and V. parahaemolyticus (P = 0.23) isolated from the oysters collected before versus after relaying. This suggests that the salinity of the relaying sites did not affect the AMS profiles of the Vibrio isolates, although it did reduce the numbers of these bacteria in oysters (S. Parveen et al., J Food Sci 82:484–491, 2017, https://doi.org/10.1111/1750-3841.13584).
Modeling aqueous solvation with semi-explicit assembly

We describe a computational solvation model called semi-explicit assembly (SEA). SEA water captures much of the physics of explicit-solvent models but with computational speeds approaching those of implicit-solvent models. We use an explicit-water model to precompute properties of water solvation shells around simple spheres, then assemble a solute’s solvation shell by combining the shells of these spheres. SEA improves upon implicit-solvent models of solvation free energies by accounting for local solute curvature, accounting for near-neighbor nonadditivities, and treating water’s dipole as being asymmetrical with respect to positive or negative solute charges. SEA does not involve parameter fitting, because parameters come from the given underlying explicit-solvation model. SEA is about as accurate as explicit simulations as shown by comparisons against four different homologous alkyl series, a set of 504 varied solutes, solutes taken retrospectively from two solvation-prediction events, and a hypothetical polar-solute series, and SEA is about 100-fold faster than Poisson–Boltzmann calculations.
Smokers' use of nicotine replacement therapy for reasons other than stopping smoking: findings from the ITC Four Country Survey.

AIMS To measure the prevalence and correlates of nicotine replacement therapy (NRT) use for reasons other than quitting smoking among smokers in four countries. DESIGN AND SETTING Population-based, cross-sectional telephone survey with nationally representative samples of adult smokers in Canada, the United States, the United Kingdom and Australia, conducted in 2005. PARTICIPANTS A total of 6532 adult daily smokers in Canada (n = 1660), the United States (n = 1664), the United Kingdom (n = 1617) and Australia (n = 1591). MEASUREMENTS Survey questions included demographics, smoking behaviour, use of NRT and reasons for NRT use, as well as access and availability of NRT. FINDINGS Approximately 17% of smokers surveyed had used NRT in the past year. Among NRT users, approximately one-third used NRT for a reason other than quitting smoking, including temporary abstinence or reducing the number of cigarettes smoked. The prevalence of non-standard NRT use was remarkably consistent across countries. Using NRT for reasons other than quitting was associated with higher education level, heavier smoking, having no quit intentions, having no past-year quit attempts, the type of NRT product used and accessing NRT without a prescription. CONCLUSIONS The use of NRT for purposes other than quitting smoking is fairly common and may help to explain the difficulty in detecting significant quitting benefits associated with NRT use in population studies. Tobacco control policies, including the accessibility of NRT, may have important implications for patterns of NRT use.
Inhibition of Morphine‐Induced Tolerance and Dependence by a Benzodiazepine Receptor Agonist Midazolam in the Rat

We investigated whether midazolam administration influenced morphine-induced antinociception and tolerance and dependence in the rat. Antinociception was assessed by the tail-flick (TF) and the hot-plate test (HP 52°C). Morphine tolerance developed after daily single injections of morphine for 11 days. The effect of midazolam on morphine-induced antinociception and tolerance was assessed by giving daily injections of various doses of midazolam for 11 days. The first injection of saline or midazolam was given intraperitoneally and 30 min later morphine (10 mg/kg body weight) was administered subcutaneously. Antinociception was monitored by measuring TF and HP latencies 60 min after the second injection. Midazolam was injected at four different concentrations: 0.03, 0.1, 0.3, and 3 mg/kg body weight. Chronic administration of morphine resulted in the development of tolerance to antinociception in both TF and HP tests, with rats exhibiting baseline antinociception on Day 9. Animals treated with midazolam alone showed little antinociception on Days 3–9. However, midazolam administration in morphine-treated animals attenuated morphine-induced tolerance to antinociception on Days 1–11 as measured by the tail-flick test. Midazolam also decreased the jumping behavior following naloxone injections in morphine-dependent rats. These results suggest that midazolam may prolong the effects of morphine by delaying morphine-induced development of tolerance to antinociception. Midazolam also attenuated a decrease in weight gain induced by chronic injections of morphine.
U.S. Regional Housing Bubbles, Their Co-Movements and Spillovers

This paper provides the first empirical evidence for co-movement and spillover effects of regional housing bubbles. In our two-stage identification strategy, we first decompose the observed housing price into a fundamental and a bubble component. We then analyze the interdependence among these regional bubble series using spatial econometric methods. The empirical results indicate that a regional bubble first affects the nearby regions via geographical proximity. Spillover effects reinforce the influence on nearby regions. Similar economic and financial conditions help spread the bubble across regions. Simulation results reveal that the diffusion process will be amplified by a bubble’s intrinsic dynamics as well as by market price expectations. We conclude that a regional housing bubble is of more than regional interest because it may infect numerous other regions and also cause nationwide problems through wealth and multiplier effects once it bursts.
Fixed‐ratio size as a determinant of tolerance to cocaine: is relative or absolute size important?

Six studies, examining five drugs in three species, have demonstrated that tolerance development is impaired under relatively long fixed-ratio (FR) schedules compared with relatively short FR schedules. One such study demonstrated that substantial tolerance to the rate-reducing effects of cocaine in pigeons developed under the FR 5 and 25 components of a multiple schedule of food delivery, but little or no tolerance developed under the FR 125 component. The present study examined the acute and chronic effects of cocaine in three groups of pigeons. One group was exposed to a simple FR 5 schedule of food delivery, a second to a simple FR 125 schedule of food delivery, and a third to a simple FR 125 schedule that alternated across sessions with a multiple FR 125 FR 250 schedule. When administered acutely, cocaine (1–10 mg/kg) produced dose-dependent rate decreases under all schedules. With chronic exposure to 5.56 mg/kg cocaine, tolerance clearly developed under the FR 5 schedule. Evidence of tolerance under the FR 125 schedule was equivocal, but strongest when that schedule alternated with an FR 250 component under a multiple schedule arrangement. There was no consistent evidence of tolerance under the FR 250 component. These results suggest that, although the development of tolerance under an FR schedule may be affected by exposure to a longer schedule, tolerance to cocaine does not develop readily under “long” FR schedules, regardless of the context in which they appear
Fine specificity of the anti-citrullinated protein antibody response is influenced by the shared epitope alleles.

OBJECTIVE In classic studies on the genetic background of antibody production, the major histocompatibility complex (MHC) has been shown to act as the most prominent immune response gene that controls the magnitude and the specificity of antibody production. The strongest genetic risk factor for rheumatoid arthritis (RA), the human MHC HLA-DRB1 shared epitope (SE) alleles, predisposes for antibodies against citrullinated proteins (ACPAs). ACPA levels are higher in SE-positive patients with RA than in SE-negative patients with RA. The aim of the present study was to determine whether SE influences not only the magnitude but also the specificity of the ACPA response. METHODS In 2 cohorts of anti-citrullinated peptide 2-positive patients with RA, one from a study of recent-onset arthritis (n = 206) and the other from a treatment strategy study (n = 141), serum antibodies against a citrullinated peptide derived from vimentin (cVim) and antibodies against a citrullinated fibrinogen peptide (cFibr) were determined by enzyme-linked immunosorbent assay. HLA-DRB1 genotyping was performed. RESULTS In the first cohort, SE alleles were significantly associated with the presence of antibodies against cVim (odds ratio [OR] 4.95, 95% confidence interval [95% CI] 1.87-15.3) and were not significantly associated with the presence of antibodies against cFibr (OR 1.71, 95% CI 0.70-4.14). These results were replicated in the second cohort (OR 5.05, 95% CI 1.92-13.6 and OR 1.19, 95% CI 0.30-3.97, respectively). CONCLUSION In 2 cohorts of ACPA-positive patients with RA, SE alleles predisposed for the development of antibodies against cVim but not for the development of antibodies against cFibr. These data indicate that SE alleles act as "classic" immune response genes in the ACPA response, because they influence both the magnitude and the specificity of this RA-specific antibody response.
Panic symptoms in schizophrenia: Comorbidity and clinical correlates

Abstract The aim of the present study was to investigate the prevalence of panic attack (PA) and panic disorder (PD) in patients with schizophrenia and detect the clinical features. Forty‐nine patients with schizophrenia were included in the study. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), Extrapyramidal Symptom Rating Scale (ESRS) and Bandelow Panic and Agoraphobia Rating Scale were administered. Fifteen patients were found to have PA and seven patients had PD. Patients with panic symptoms had higher scores of PANSS, HDRS, CGI and ESRS. Comorbid panic symptoms in schizophrenia may be related to positive symptoms, extrapyramidal side‐effects and depression.
Hepatotoxicity Associated with Chinese Skullcap Contained in Move Free Advanced Dietary Supplement: Two Case Reports and Review of the Literature

Move Free Advanced is a widely available dietary supplement in the United States, marketed to comfort sore joints and improve flexibility and mobility. This product contains glucosamine, chondroitin, hyaluronic acid, and Uniflex proprietary extract, which is a combination of Chinese skullcap and black catechu. We describe two patients who developed hepatotoxicity after ingesting a Move Free Advanced product. In both patients, the hepatotoxicity resolved after discontinuation of the supplement. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6 for both patients) between the patients' development of hepatotoxicity and the Move Free Advanced supplement. Based on a review of the literature, the herbal extract Chinese skullcap is the most likely cause of the hepatotoxicity. To our knowledge, these two cases are the first to be published regarding possible hepatotoxicity associated with Move Free Advanced. Patients seeking dietary supplements for osteoarthritis may want to avoid glucosamine‐chondroitin products such as Move Free Advanced that also contain Chinese skullcap.
La convergencia regional en Colombia : una visión de largo plazo, 1926-1995

Muestra una vision de largo plazo del proceso de convergencia y polarizacion regional en Colombia. Para ello se estudia el periodo que va desde 1926 hasta 1995, dividiendolo en dos subperiodos de acuerdo con las fuentes estadisticas disponibles. El primer subperiodo esta comprendido entre 1926 y 1960. El segundo subperiodo va de 1960 a 1995. La convergencia se estudia a partir de la informacion sobre PIB departamental disponible. Finalmente, se presentan las principales conclusiones del estudio.
Alterations in vascular architecture and permeability following OXi4503 treatment

OXi4503 retards tumor growth in a dose-dependent manner and improves survival in a murine model of colorectal liver metastases. This agent causes extensive vascular shutdown by selectively altering the tubulin cytoskeleton within the endothelial cells of tumor vessels. The destruction of tumor vessels is incomplete, however, and tumor revascularization occurs after the treatment. This study evaluates the pattern of microcirculatory changes and alterations to the ultrastructural properties of the tumor vasculature that result from OXi4503 treatment. Male CBA mice were induced with liver metastases via an intrasplenic injection of a murine-derived colorectal cell line. After administering a single intraperitoneal dose of OXi4503, changes in tumor perfusion, microvascular architecture and permeability were assessed at various time points. One hour after a 100-mg/kg dose of OXi4503, a significant decrease in the percentage of tumor perfusion (63.96±1.98 in controls versus 43.77±2.71 in treated mice, P<0.001) was observed, which was still evident 5 days after the treatment. Substantial tumor microvascular damage and minimal normal liver injury were observed. Tumor vascular permeability was significantly elevated 45 min after the OXi4503 treatment (67.5±3.60 in controls versus 80.5±2.24 μg/g, P<0.05). The findings suggest that OXi4503 selectively targets tumor vessels and causes immediate microvascular destruction. Even at the maximum tolerated dose, however, residual patent tumor vessels were still present after treatment, implying incomplete tumor destruction. A combination of OXi4503 with other chemotherapeutic modalities might achieve complete tumor eradication and improve long-term survival.
Cell Division and Maintenance of Epithelial Integrity in the Deafened Auditory Epithelium

Quiescence is among the hallmarks of the sensory epithelium of the cochlea. When auditory sensory cells (hair cells) degenerate they are not replaced, and therefore hearing loss is permanent. Cochlear hair cells are susceptible to several types of lesions, including aminoglycoside antibiotics. The application of the aminoglycoside neomycin in the inner ear mimics cases of severe hair cell loss and leads to collapse of the cochlear epithelium. We now report that in mature guinea pig cochleae injected with neomycin, the remaining non-sensory cells undergo a robust proliferative response. p27Kip1, an inhibitor of cell cycle in the cochlea, was present in non-dividing cells and absent during mitosis. Dividing cells retained their tight junction complexes and maintained the structural confluence of the auditory epithelium during cell division. The plane of mitosis was invariably parallel to the luminal surface. These results indicate that the flat epithelium of the cochlea can down-regulate p27Kip1 and divide after a severe lesion and suggest that the cell divisions assist in maintaining the epithelial confluence throughout the cochlea. Presence of mitosis in the tissue presents therapeutic opportunities for gene transfer and stem cells therapies.
Developmental basis of severe neural tube defects in the loop-tail (Lp) mutant mouse: use of microsatellite DNA markers to identify embryonic genotype.

Mouse embryos homozygous for the mutation loop-tail (Lp) develop lethal defects in which the neural tube remains open from the hindbrain to the caudal extremity, a condition that closely resembles the human malformation craniorachischisis. Heterozygotes develop tail defects and occasional spina bifida, but are generally viable. In order to study the early development of these defects, it is necessary to determine the genotype of embryos at stages prior to the first appearance of the morphological abnormalities. We used a microsatellite DNA sequence, Crp, that is closely linked to the Lp locus and which segregates polymorphic variants in matings between Lp/+ mice, thus permitting identification of embryos of Lp/Lp, Lp/+ and +/+ genotypes. We found that the severe phenotype craniorachischisis is present at 9.5 and 10.5 days of gestation only in Lp/Lp embryos in utero, whereas Lp/+ and +/+ littermates show neural tube closure throughout most of the body axis. The open neural tube phenotype also develops in Lp/Lp embryos growing in whole embryo culture. A small proportion of Lp/+ embryos were found to develop this phenotype in vitro, but only when culture conditions were suboptimal. Analysis of 8.5-day embryos revealed that the initial defect in Lp/Lp embryos is failure to initiate neural tube closure at the cervical/hindbrain boundary when the embryo has 6-7 somites. Thereafter, the neural tube remains open throughout the body axis, with the exception of the midbrain and forebrain where neural tube closure is initiated independently. Closure at the midbrain/forebrain boundary does not appear to be defective in Lp/Lp embryos. Heterozygous Lp/+ embryos initiate neural tube closure at the cervical/hindbrain boundary with a slight delay compared with +/+ littermates. Moreover, at 10.5 days of gestation, Lp/+ embryos undergo delayed closure of the posterior neuropore. Thus, Lp/+ embryos are defective in several aspects of the neurulation process. The pattern of delayed neuropore closure in Lp/+ embryos resembles that caused by the ct and Sp mutations and is likely to be responsible for the development of tail defects (i.e., looped tails) and spina bifida in Lp/+ mice. The use of microsatellite markers to determine the genotype of mutant embryos has general application: microsatellites are widespread throughout the mouse genome, so that informative sequences are likely to be available with close linkage to the majority of mutant genes. Moreover, polymorphisms can be detected using the polymerase chain reaction, making it possible to determine the genotype of very early embryos when only small amounts of material are available.
Peer Monitoring, Syndication, and the Dynamics of Venture Capital Interactions: Theory and Evidence

We develop a theoretical model providing a new rationale for venture capitalist (VC) syndicate formation and empirically test our model predictions. An entrepreneur obtains financing and two different value-adding inputs from a single VC or from two different VCs, each operating in his area of expertise. We characterize the entrepreneur’s equilibrium choice between contracting with a single VC, individually with multiple VCs, or with a VC syndicate. We show that syndicates mitigate VCs’ moral hazard problem in value addition. We also analyze the dynamics of VC syndicate composition. The results of our empirical analysis are consistent with our model’s predictions.
Dapsone for autoimmune thrombocytopenic purpura

Twenty‐one human immunodeficiency virus (HIV)‐free and six HIV‐infected adults with autoimmune thrombocytopenic purpura (AITP) were treated with dapsone (100 mg/day). A response was observed in 13 patients (median platelet count before 25 × 109/L, range 3–49; after 109 × 109/L, range 69–241). Thrombocytopenia recurred in four of the responders in whom dapsone was discontinued. No response was observed in 12 patients. Dapsone had to be withdrawn after two weeks of treatment in the remaining two patients and after six to eight weeks in three other patients due to intolerance. No serious hematological complications were observed. These results confirm that dapsone is a safe, inexpensive, and effective treatment of AITP. © 1993 Wiley‐Liss, Inc.