Miracle-dz/UniFAR-FTUs huggingface dataset:
Granulysin, a Cytolytic Molecule, Is Also a Chemoattractant and Proinflammatory Activator 1

Granulysin, a cationic protein produced by activated human CTL and NK cells, is cytolytic against microbial and tumor targets. In this study we show that granulysin also functions as a chemoattractant and activates monocytes to produce cytokines/chemokines. Although granulysin-mediated cytotoxicity occurs at micromolar concentrations, chemoattraction occurs in the nanomolar range, and immune activation occurs over a wide range of concentrations (nanomolar to micromolar). Granulysin causes a 2- to 7-fold increase in chemotaxis of monocytes, CD4+, and CD8+ memory (CD45RO) but not naive (CD45RA) T cells, NK cells, and mature, but not immature, monocyte-derived dendritic cells. Pertussis toxin treatment abrogates chemoattraction by granulysin, indicating involvement of G-protein-coupled receptor(s). At low concentrations (10 nM), granulysin promotes a 3- to 10-fold increase in MCP-1 and RANTES produced by monocytes and U937 cells, while a 2-fold increase in TNF-α production by LPS-stimulated monocytes requires higher concentrations of granulysin (micromolar). Taken together, these data indicate that the local concentration of granulysin is critical for the biologic activity, with high concentrations resulting in cytotoxicity while lower concentrations, presumably further from the site of granulysin release, actively recruit immune cells to sites of inflammation.
Sex differences in brain‐derived neurotrophic factor signaling: Functions and implications

Brain‐derived neurotrophic factor (BDNF) regulates diverse processes such as neuronal survival, differentiation, and plasticity. Accumulating evidence suggests that molecular events that direct sexual differentiation of the brain interact with BDNF signaling pathways. This Mini‐Review first examines potential hormonal and epigenetic mechanisms through which sex influences BDNF signaling. We then examine how sex‐specific regulation of BDNF signaling supports the development and function of sexually dimorphic neural circuits that underlie male‐specific genital reflexes in rats and song production in birds. Finally, we discuss the implications of sex differences in BDNF signaling for gender‐biased presentation of neurological and psychiatric diseases such as Alzheimer's disease. Although this Mini‐Review focuses on BDNF, we try to convey the general message that sex influences brain functions in complex ways and underscore the requirement for and challenge of expanding research on sex differences in neuroscience. © 2016 Wiley Periodicals, Inc.
Incorporating missingness for estimation of marginal regression models with multiple source predictors

Multiple informant data refers to information obtained from different individuals or sources used to measure the same construct; for example, researchers might collect information regarding child psychopathology from the child's teacher and the child's parent. Frequently, studies with multiple informants have incomplete observations; in some cases the missingness of informants is substantial. We introduce a Maximum Likelihood (ML) technique to fit models with multiple informants as predictors that permits missingness in the predictors as well as the response. We provide closed form solutions when possible and analytically compare the ML technique to the existing Generalized Estimating Equations (GEE) approach. We demonstrate that the ML approach can be used to compare the effect of the informants on response without standardizing the data. Simulations incorporating missingness show that ML is more efficient than the existing GEE method. In the presence of MCAR missing data, we find through a simulation study that the ML approach is robust to a relatively extreme departure from the normality assumption. We implement both methods in a study investigating the association between physical activity and obesity with activity measured using multiple informants (children and their mothers). Copyright © 2006 John Wiley & Sons, Ltd.
The Stereotype Consistency Effect Is Moderated by Group Membership and Trait Valence

ABSTRACT People generally have better memories for traits that are stereotypic consistent rather than stereotypic inconsistent. From social identity theory, we hypothesized that this stereotype consistency effect would be moderated by group membership and trait valence. Specifically, we expected the typical stereotype-consistency effect when the target person was an outgroup member (different ethnicity from the participant). However, if the target person was an ingroup member (same ethnicity as the participant), we expected stereotypicality to facilitate memory for positive traits but not negative traits. Participants (N = 104) read a series of statements about an ingroup member or an outgroup member and subsequently completed a memory test. The results confirmed our main prediction. The findings have implications for social identity theory, social cognition research, and for understanding intergroup relations.
Disruption of Heparan and Chondroitin Sulfate Signaling Enhances Mesenchymal Stem Cell‐Derived Osteogenic Differentiation via Bone Morphogenetic Protein Signaling Pathways

Cell surface heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans have been implicated in a multitude of biological processes, including embryonic implantation, tissue morphogenesis, wound repair, and neovascularization through their ability to regulate growth factor activity and morphogenic gradients. However, the direct role of the glycosaminoglycan (GAG) sugar‐side chains in the control of human mesenchymal stem cell (hMSC) differentiation into the osteoblast lineage is poorly understood. Here, we show that the abundant cell surface GAGs, HS and CS, are secreted in proteoglycan complexes that directly regulate the bone morphogenetic protein (BMP)‐mediated differentiation of hMSCs into osteoblasts. Enzymatic depletion of the HS and CS chains by heparinase and chondroitinase treatment decreased HS and CS expression but did not alter the expression of the HS core proteins perlecan and syndecan. When digested separately, depletion of HS and CS chains did not effect hMSC proliferation but rather increased BMP bioactivity through SMAD1/5/8 intracellular signaling at the same time as increasing canonical Wnt signaling through LEF1 activation. Long‐term culturing of cells in HS‐ and CS‐degrading enzymes also increased bone nodule formation, calcium accumulation, and the expression of such osteoblast markers as alkaline phosphatase, RUNX2, and osteocalcin. Thus, the enzymatic disruption of HS and CS chains on cell surface proteoglycans alters BMP and Wnt activity so as to enhance the lineage commitment and osteogenic differentiation of hMSCs.
The capacity of unstable dynamical systems-interaction of control and information transmission

Feedback capacity is extended beyond classical communication channels, to stochastic dynamical systems, which may correspond to unstable control systems or unstable communication channels, subject to average cost constraints of total power κ e [0, to). It is shown that optimal conditional distributions or randomized strategies, have a dual role, to simultaneously control the output process and to encode information. The dual role is due to the interaction of control and information transmission; it states that encoders in communication channels operate as encoders-controllers, while controllers in control systems operate as controllers-encoders. The concepts are illustrated through the analysis of Gaussian control systems with randomized strategies, which are equivalent to Additive Gaussian Noise channels, Stable or Unstable, with arbitrary memory on past outputs, with an average constraint of quadratic form. It is shown that such unstable dynamical systems have Control-Coding Capacity which is operational, precisely as in Shannon's operational definition. However, the control-coding capacity is zero, unless the power κ allocated to the system, exceeds a threshold Kmin, where Kmin is the minimum cost of ensuring asymptotic stability and ergodicity. The excess power κ — Kmin is turned into an achievable rate of information transmission over the dynamical system.
Major Neutralizing Sites on Vaccinia Virus Glycoprotein B5 Are Exposed Differently on Variola Virus Ortholog B6

ABSTRACT Immunization against smallpox (variola virus) with Dryvax, a live vaccinia virus (VV), was effective, but now safety is a major concern. To overcome this issue, subunit vaccines composed of VV envelope proteins from both forms of infectious virions, including the extracellular enveloped virion (EV) protein B5, are being developed. However, since B5 has 23 amino acid differences compared with its B6 variola virus homologue, B6 might be a better choice for such a strategy. Therefore, we compared the properties of both proteins using a panel of monoclonal antibodies (MAbs) to B5 that we had previously characterized and grouped according to structural and functional properties. The B6 gene was obtained from the Centers for Disease Control and Prevention, and the ectodomain was cloned and expressed in baculovirus as previously done with B5, allowing us to compare the antigenic properties of the proteins. Polyclonal antibodies to B5 or B6 cross-reacted with the heterologous protein, and 16 of 26 anti-B5 MAbs cross-reacted with B6. Importantly, 10 anti-B5 MAbs did not cross-react with B6. Of these, three have important anti-VV biologic properties, including their ability to neutralize EV infectivity and block comet formation. Here, we found that one of these three MAbs protected mice from a lethal VV challenge by passive immunization. Thus, epitopes that are present on B5 but not on B6 would generate an antibody response that would not recognize B6. Assuming that B6 contains similar variola virus-specific epitopes, our data suggest that a subunit vaccine using the variola virus homologues might exhibit improved protective efficacy against smallpox.
Dividend Change, Institutional Ownership and Shareholder Wealth

I test whether taxes affect shareholder wealth around dividend change announcements. I control for the magnitude of the dividend tax penalty and the identity of a tax advantaged investor, proxied for by the level of institutional ownership. Consistent with my argument, I find that 1) a dividend tax penalty erodes the positive wealth effect of dividend; 2) the presence of a tax advantaged marginal investor mitigates the negative dividend tax effect. My results offer evidence that shareholder level taxes impact asset prices. I contribute to the literature by separating the dividend tax effect from its information effect.
Discovery and characterization of single nucleotide polymorphisms in Chinook salmon, Oncorhynchus tshawytscha

Molecular population genetics of non‐model organisms has been dominated by the use of microsatellite loci over the last two decades. The availability of extensive genomic resources for many species is contributing to a transition to the use of single nucleotide polymorphisms (SNPs) for the study of many natural populations. Here we describe the discovery of a large number of SNPs in Chinook salmon, one of the world’s most important fishery species, through large‐scale Sanger sequencing of expressed sequence tag (EST) regions. More than 3 Mb of sequence was collected in a survey of variation in almost 132 kb of unique genic regions, from 225 separate ESTs, in a diverse ascertainment panel of 24 salmon. This survey yielded 117 TaqMan (5′ nuclease) assays, almost all from separate ESTs, which were validated in population samples from five major stocks of salmon from the three largest basins on the Pacific coast of the contiguous United States: the Sacramento, Klamath and Columbia Rivers. The proportion of these loci that was variable in each of these stocks ranged from 86.3% to 90.6% and the mean minor allele frequency ranged from 0.194 to 0.236. There was substantial differentiation between populations with these markers, with a mean FST estimate of 0.107, and values for individual loci ranging from 0 to 0.592. This substantial polymorphism and population‐specific differentiation indicates that these markers will be broadly useful, including for both pedigree reconstruction and genetic stock identification applications.
Rational Inattention-driven dispersion over the business cycle

This paper develops a model in which firms acquire costly information to make pricing decisions. Prices are set by tracking an unobserved target whose volatility depends on a persistent state of the economy. Firms are Rationally Inattentive since they face different information processing costs when learning the target. By embedding heterogeneous time-invariant information costs in this persistent volatility setting, I show that the model endogenously generates countercyclical dispersion in price changes, as documented by re- cent empirical findings. Costly information generates a delay in the rate at which firms’ recognize any change of state, leading to different pricing decisions through the transition. Endogenous information and heterogeneous costs alone are enough to replicate the empirical time-varying evolution of the dispersion of price changes, as well as the positive co-movement between the dispersion and frequency of price changes.
Impact of Policy Changes on Emergency Department Use by Medicaid Enrollees in Oregon

Objective:In 2003, Oregon's Medicaid expansion program, the Oregon Health Plan (OHP), implemented premiums and copayments and eliminated outpatient behavioral health services. We ascertained whether these changes, including $50 copayments for emergency department (ED) visits, affected ED use. Methods:This study used statewide administrative data on 414,009 adult OHP enrollees to compare ED utilization rates (adjusted for patient characteristics) in 3 time periods: (1) before the cutbacks, (2) after the cutbacks, and (3) after partial restoration of benefits. We examined overall ED visits and several subsets of ED visits: visits requiring hospital admission, injury-related, drug-related, alcohol-related, and other psychiatric visits. Because the policy changes affected only the expansion program (OHP Standard), we ascertained the impact of these changes compared with a control group of categorically eligible Medicaid enrollees (OHP Plus). Results:Compared with the control group, case-mix-adjusted ED utilization rates fell 18% among OHP Standard enrollees after the cutbacks. The rate of ED visits leading to hospitalization fell 24%. Injury-related visits and psychiatric visits excluding chemical dependency exhibited a similar pattern to overall ED visits. Drug-related ED visits increased 32% in the control group, perhaps reflecting the closure of drug treatment programs after the cutbacks reduced their revenue. Conclusion:The policy changes were followed by a substantial reduction in ED use. That ED visits requiring hospital admission fell to about the same extent as overall ED use suggests that OHP enrollees may have been discouraged from using EDs for emergencies as well as less-serious problems.
Spatial conscript body height correlation of Norwegian districts in the 19th century.

ABSTRACT Background: We investigated height of Norwegian conscripts in view of the hypothesis of a "community effect on height" using autocorrelation analysis of district heights within a time-span of 20 years at the end of the 19th century and correlations between neighboring districts at this time. Material and methods: After digitalizing available body height data of Norwegian draftees in 1877-1878, 1880 (averaged as 1878), and 1895-1897 (averaged as 1896) we calculated the magnitude of autocorrelation of body height within the same municipality at different time points. Furthermore, we generated three different neighborhood networks, (1) based on Euclidean distances, (2) a minimum spanning tree build on those distances, (3) a network founded on real world road connections. The networks were used to determine the correlation between body height of neighboring districts depending on the number of edges required to connect two municipalities. Results: The autocorrelation value for body heights was around r = 0.5 (for all p < 0.001) in the years 1878 and 1896. The correlation between neighboring districts varied in the Euclidean distance based network between 0.47 and 0.27 approximately for both years in a sorted order, descending from nearest (0-50 km) to farthest (150-200 km, for all p < 0.001). First order neighbors in the minimum spanning tree network correlation was 0.36 in 1878 and 0.42 in 1896 (for all p < 0.001). The values of neighbor correlation in the road connection based network ranged in 1878 from 0.42 (first order neighbors) to 0.17 (forth order neighbors, for all p < 0.01) and in 1896 from 0.46 (first order neighbors) to 0.12 (forth order neighbors, for all p < 0.05). Conclusion: This initial study of Norwegian conscript height data from the 19th century showed significant medium sized effects for the within district autocorrelation between 1878 and 1896 as well as medium neighborhood correlation, slightly lower in comparison to a recent study regarding Swiss conscripts. Digitalizing more data from other years in this and later time spans as well as using older road and ship connections instead of the actual road data might stabilize and improve those findings.
Concomitant herbal medicine and Antiretroviral Therapy (ART) use among HIV patients in Western Uganda: A cross-sectional analysis of magnitude and patterns of use, associated factors and impact on ART adherence

Abstract Use of herbal medicines among patients receiving Anti-retroviral Therapy (ART) remains by far an uncharacterised phenomenon in Africa and Uganda specifically. We evaluated the use of herbal medicines among patients on ART at the HIV clinic of Mbarara Regional Referral Hospital (MRRH), examined factors associated with their concomitant use and their impact on ART adherence. This was a cross-sectional study among 334 systematically sampled patients receiving ART at the HIV clinic of MRRH from February to April 2010. We collected data on patient demographics, clinical characteristics, perceptions of quality of care received, self-perceived health status, information on ART received, herbal medicines use and ART adherence. Study outcomes were concomitant herbal medicine and ART use, and ART adherence. Descriptive analysis and logistic regression were conducted using Stata10.0. Close to half, 155 (46.4%) reported concomitant herbal medicines and ART use, with 133 (39.8%) using herbal medicines at least once daily. Most (71.6%) used herbal medicines to treat HIV-related symptoms. A majority (92.3%) reported that the doctors were unaware of their use of herbal medicines, 68.5% citing its minimal importance to the attending physician. Most frequently used herbs were Aloe vera (25%) and Vernonia amygdalina (21%). Time since start of ART (OR 1.14 95% CI: 1.01–1.28, for each one year increase), number of ART side effects reported (≥3 vs.≤1, OR 2.20 95% CI 1.13–4.26) and self-perceived health status (Good vs. Poor, OR 0.31 95% CI 0.12–0.79) were independently associated with concomitant herbal medicine and ART use. Concomitant herbal medicine and ART use was not associated with poor ART adherence (OR 0.85 95% CI 0.47–1.53). There is widespread concomitant herbal medicines and ART use among our patients, with no association to poor ART adherence. Patients appear to use these therapies to complement as opposed to substituting ART.
Distribution of cell-free and cell-associated HIV surrogates in the female genital tract after simulated vaginal intercourse.

BACKGROUND Rational development of drugs to prevent human immunodeficiency virus (HIV) transmission benefits from an understanding HIV distribution in the female genital tract after intercourse. This study describes HIV distribution using surrogates of cell-free and cell-associated HIV and semen. METHODS Apheresis-derived, autologous, lymphocyte-rich cells radiolabeled with 3.7-MBq (100-μCi) indium 111 ((111)In)-oxine (cell-associated HIV surrogate) and 18.5-MBq (500-μCi) technetium 99m ((99m)Tc)-sulfur colloid (HIV-sized 100-nm particle, cell-free HIV surrogate) were resuspended in 3 mL of hydroxyethylcellulose gel (semen simulant) with gadoteridol and dosed via artificial phallus after simulated intercourse. Postdosing dual-isotope single photon emission computed tomography with computed tomography (SPECT/CT) and magnetic resonance (MR) images were acquired to determine the surrogates' distribution. Seven hours after dosing, vaginal biopsy and luminal samples were collected at discrete locations in 8 subjects. RESULTS SPECT/CT and MR analysis showed HIV and semen surrogate distribution with highest signal intensity in the vaginal pericervical area, without detectable signal in the uterus. One-third of the administered dose was retained in the female genital tract after 4 hours. Cell-free and cell-associated surrogate distribution coincided. CONCLUSIONS We demonstrate the feasibility of dual-isotope SPECT/CT and MR imaging to determine the distribution of HIV and semen surrogates after simulated intercourse without disrupting vaginal contents. Surrogate distribution suggests topical microbicides do not need to reach the uterus for efficacy.
Effect of melatonin treatment on 24‐hour rhythms of serum ACTH, growth hormone, prolactin, luteinizing hormone and insulin in rats injected with Freund's adjuvant

Abstract: The effect of melatonin injection on Freund's adjuvant‐induced changes in levels and 24‐hr rhythms of circulating ACTH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and insulin was assessed in rats. Animals received subcutaneous (s. c.) injections of melatonin (30 ug) or vehicle, 1 hr before lights off for 12 days. Ten days after melatonin treatment, they were injected with Freund's complete adjuvant or its vehicle s. c. , and after 3 days, rats were killed at six different time intervals throughout a 24‐hr cycle to measure the different hormones by radioimmunoassay (RIA). Following Freund's adjuvant injection, an increase in serum ACTH, with maintenance of ACTH diurnal rhythm was found. Acrophases of the ACTH rhythm varied from 13: 39 to 17:12 hr and the amplitude of rhythm was augmented after immunization. In immunized rats, melatonin treatment increased the amplitude of serum ACTH rhythm. For GH, a depressive effect of immunization on circulating levels, together with absence of diurnal rhythmicity were found. Immunization augmented circulating PRL, while conserving its diurnal rhythmicity. Melatonin‐injected rats showed significant diurnal variations of serum PRL after immunization only. Acrophases of the serum PRL rhythm varied from 19: 37 to 22:04 hr. Immunization decreased circulating LH and suppressed its 24‐hr rhythmicity pattern. The effect of immunization on LH was counteracted by melatonin injection. Acrophases of serum LH rhythm varied from 00:44 to 03:53 hr. Significant effects of immunization and time of day on circulating insulin were detected; immunization increased serum insulin levels with a shift in acrophase from early afternoon to midnight. The data indicate that several early changes in levels and 24‐hr rhythms of circulating ACTH, PRL, and LH in Freund's adjuvant‐injected rats were sensitive to treatment with pharmacological amounts of melatonin.