Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness

The serotonin-1A (5-HT1A) receptor is among the most abundant and widely distributed 5-HT receptors in the brain, but is also expressed on serotonin neurons as an autoreceptor where it plays a critical role in regulating the activity of the entire serotonin system. Over-expression of the 5-HT1A autoreceptor has been implicated in reducing serotonergic neurotransmission, and is associated with major depression and suicide. Extensive characterization of the transcriptional regulation of the 5-HT1A gene (HTR1A) using cell culture systems has revealed a GC-rich "housekeeping" promoter that non-selectively drives its expression; this is flanked by a series of upstream repressor elements for REST, Freud-1/CC2D1A and Freud-2/CC2D1B factors that not only restrict its expression to neurons, but may also regulate the level of expression of 5-HT1A receptors in various subsets of neurons, including serotonergic neurons. A separate set of allele-specific factors, including Deaf1, Hes1 and Hes5 repress at the HTR1A C(-1019)G (rs6295) polymorphism in serotonergic neurons in culture, as well as in vivo. Pet1, an obligatory enhancer for serotonergic differentiation, has been identified as a potent activator of 5-HT1A autoreceptor expression. Taken together, these results highlight an integrated regulation of 5-HT1A autoreceptors that differs in several aspects from regulation of post-synaptic 5-HT1A receptors, and could be selectively targeted to enhance serotonergic neurotransmission

Can Information Widen Socioeconomic Gaps in Postsecondary Aspirations? How College Costs and Returns Affect Parents’ Preferences for Their Children

To estimate whether information can close socioeconomic gaps in parents’ aspirations for their child’s postsecondary education, we administer a four-armed survey experiment to a nationally representative sample of U.S. parents. After respondents estimate costs of and returns to further education, we ask whether they prefer that their child pursue a four-year degree, a two-year degree, or no further education. Before this question is posed, the treated are first told:(1) the net annual costs of pursuing a four-year and two-year degree in their state,(2) the annual returns to four-year and two-year degrees as compared to no further education in their local area, or(3) both costs and returns. We find that information lowers aspirations overall and widens socioeconomic aspiration gaps.These effects do not vary with the magnitude of error between estimated and actual costs and returns. However, we find positive impacts on aspirations among parents who think their child is academically prepared for college

Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analogues display remarkable potency to activate latent HIV without global T-cell activation

AbstractCurrent antiretroviral therapy (ART) for HIV/AIDS slows disease progression by reducing viral loads and increasing CD4 counts. Yet ART is not curative due to the persistence of CD4+ T-cell proviral reservoirs that chronically resupply active virus. Elimination of these reservoirs through the administration of synergistic combinations of latency reversing agents (LRAs), such as histone deacetylase (HDAC) inhibitors and protein kinase C (PKC) modulators, provides a promising strategy to reduce if not eradicate the viral reservoir. Here, we demonstrate that largazole and its analogues are isoform-targeted histone deacetylase inhibitors and potent LRAs. Significantly, these isoform-targeted HDAC inhibitors synergize with PKC modulators, namely bryostatin-1 analogues (bryologs). Implementation of this unprecedented LRA combination induces HIV-1 reactivation to unparalleled levels and avoids global T-cell activation within resting CD4+ T-cells.</jats:p

Comparative Analysis of Combinations of Dimension Reduction and Data Mining Techniques for Malware Detection

Many malware detectors utilize data mining techniques as primary tools for pattern recognition. As the number of new and evolving malware continues to rise, there is an increasing need for faster and more accurate detectors. However, for a given malware detector, detection speed and accuracy are usually inversely related. This study explores several configurations of classification combined with feature selection. An optimization function involving accuracy and processing time is used to evaluate each configuration. A real data set provided by Trend Micro Philippines is used for the study. Among 18 di↵erent configurations studied, it is shown that J4.8 without feature selection is best for cases where accuracy is extremely important. On the other hand, when time performance is more crucial, applying a Na¨ıve Bayes classifier on a reduced data set (using Gain Ratio Attribute Evaluation to select the top 35 features only) gives the best results

H-alpha Emission Variability in the gamma-ray Binary LS I +61 303

LS I +61 303 is an exceptionally rare example of a high mass X-ray binary (HMXB) that also exhibits MeV-TeV emission, making it one of only a handful of "gamma-ray binaries". Here we present H-alpha spectra that show strong variability during the 26.5 day orbital period and over decadal time scales. We detect evidence of a spiral density wave in the Be circumstellar disk over part of the orbit. The H-alpha line profile also exhibits a dramatic emission burst shortly before apastron, observed as a redshifted shoulder in the line profile, as the compact source moves almost directly away from the observer. We investigate several possible origins for this red shoulder, including an accretion disk, mass transfer stream, and a compact pulsar wind nebula that forms via a shock between the Be star's wind and the relativistic pulsar wind.Comment: Accepted to Ap

Активизация инвестиционной деятельности коммерческими банками

В статье рассмотрены основные вопросы активизации инвестиционной деятельности коммерческими банками Украины.У статті розглядаються основні питання активізації інвестиційної діяльності комерційними банками України.The main questions of the investment activity by the commercial banks of Ukraine were descried in the article

Noise kernel for a quantum field in Schwarzschild spacetime under the Gaussian approximation

A method is given to compute an approximation to the noise kernel, defined as the symmetrized connected 2-point function of the stress tensor, for the conformally invariant scalar field in any spacetime conformal to an ultra-static spacetime for the case in which the field is in a thermal state at an arbitrary temperature. The most useful applications of the method are flat space where the approximation is exact and Schwarzschild spacetime where the approximation is better than it is in most other spacetimes. The two points are assumed to be separated in a timelike or spacelike direction. The method involves the use of a Gaussian approximation which is of the same type as that used by Page to compute an approximate form of the stress tensor for this field in Schwarzschild spacetime. All components of the noise kernel have been computed exactly for hot flat space and one component is explicitly displayed. Several components have also been computed for Schwarzschild spacetime and again one component is explicitly displayed.Comment: 34 pages, no figures. Substantial revisions in Secs. I, IV, and V; minor revisions elsewhere; new results include computation of the exact noise kernel for hot flat space and an approximate computation of the noise kernel for a thermal state at an arbitrary temperature in Schwarzschild spacetime when the points are split in the time directio