Lack of neurosteroid selectivity at δ vs. γ2-containing GABAA receptors in dentate granule neurons

GAB

Econometric Measures of Connectedness and Systemic Risk in the Finance and Insurance Sectors

We propose several econometric measures of connectedness based on principal-components analysis and Granger-causality networks, and apply them to the monthly returns of hedge funds, banks, broker/dealers, and insurance companies. We find that all four sectors have become highly interrelated over the past decade, likely increasing the level of systemic risk in the finance and insurance industries through a complex and time-varying network of relationships. These measures can also identify and quantify financial crisis periods, and seem to contain predictive power in out-of-sample tests. Our results show an asymmetry in the degree of connectedness among the four sectors, with banks playing a much more important role in transmitting shocks than other financial institutions.Systemic Risk; Financial Institutions; Liquidity; Financial Crises

Experimental and theoretical study of the gas–water two phase flow through a conductance multiphase Venturi meter in vertical annular (wet gas) flow

Annular gas–liquid two phase flow widely occurs in nuclear industry. Various combinations of techniques have been employed in annular gas–liquid two phase flows to measure the flow parameters (e.g. liquid film thickness, gas volume fraction and the phase flow rates). One of the most useful techniques which has proven attractive for many multiphase flow applications is the electrical conductance technique. This paper presents an advanced conductance multiphase Venturi meter (CMVM) which is capable of measuring the gas volume fractions at the inlet and the throat of the Venturi. A new model was investigated to measure the gas flow rate. This model is based on the measurement of the gas volume fractions at the inlet and the throat of the Venturi meter using a conductance technique rather than relying on prior knowledge of the mass flow quality x. We measure conductance using two ring electrodes flush with the inner surface of the Venturi throat and two ring electrodes flush with the inner surface of the Venturi inlet. The basic operation of the electrical conductance technique in a multiphase flow is that the conductance of the mixture depends on the gas volume fraction in the water. An electronic circuit was built and calibrated to give a dc voltage output which is proportional to the conductance of the mixture which can then be related to the water film thickness in annular flow (and hence to the gas volume fraction). It was inferred from the experimental results that the minimum average percentage error of the predicted gas mass flow rates (i.e. −0.0428%) can be achieved at the optimum gas discharge coefficient of 0.932

Novel pharmacological actions of Trequinsin Hydrochloride improve human sperm cell motility and function

Background and purposeAsthenozoospermia is a leading cause of male infertility, but the development of pharmaceuticals to improve sperm motility has been hindered by the lack of effective screening platforms and knowledge of suitable molecular targets. We have demonstrated that a high throughput screening (HTS) strategy in conjunction with established in vitro tests can identify and characterise the action of compounds that improve sperm motility. The study aimed to apply HTS to identify new compounds from a novel small molecule library that increase intracellular calcium, [Ca2+]I, promote human sperm cell motility and systemically determine the mechanism of action. Experimental approach A validated HTS fluorometric [Ca2+]i assay was used to screen an in-house library of compounds. Trequinsin hydrochloride (a phosphodiesterase 3 inhibitor) was selected for detailed molecular (plate reader assays, electrophysiology and cyclic nucleotide measurement) and functional (motility and acrosome reaction) testing in sperm from healthy volunteer donors and, where possible, patients.   Key resultsThe fluorometric analysis identified Trequinsin as an efficacious agonist of [Ca2+]i, although less potent than progesterone (P4). Functionally, Trequinsin significantly increased cell hyperactivation and penetration into viscous medium in all donor sperm samples and cell hyperactivation in 22/25 (88%) patient sperm samples. The Trequinsin-induced [Ca2+]i response was cross-desensitised consistently by prostaglandin E1 but not with P4. Whole-cell patch clamp electrophysiology confirmed that Trequinsin activates CatSper and partially inhibits potassium channel activity. Trequinsin also increases intracellular cGMP.   Conclusion and Implications Trequinsin exhibits a novel pharmacological profile in human sperm and may be a suitable lead compound for the development of new pharmaceuticals to improve patient sperm function and fertilisation potential

Fundamentals of Recurrent Neural Network (RNN) and Long Short-Term Memory (LSTM) Network

Because of their effectiveness in broad practical applications, LSTM networks have received a wealth of coverage in scientific journals, technical blogs, and implementation guides. However, in most articles, the inference formulas for the LSTM network and its parent, RNN, are stated axiomatically, while the training formulas are omitted altogether. In addition, the technique of "unrolling" an RNN is routinely presented without justification throughout the literature. The goal of this paper is to explain the essential RNN and LSTM fundamentals in a single document. Drawing from concepts in signal processing, we formally derive the canonical RNN formulation from differential equations. We then propose and prove a precise statement, which yields the RNN unrolling technique. We also review the difficulties with training the standard RNN and address them by transforming the RNN into the "Vanilla LSTM" network through a series of logical arguments. We provide all equations pertaining to the LSTM system together with detailed descriptions of its constituent entities. Albeit unconventional, our choice of notation and the method for presenting the LSTM system emphasizes ease of understanding. As part of the analysis, we identify new opportunities to enrich the LSTM system and incorporate these extensions into the Vanilla LSTM network, producing the most general LSTM variant to date. The target reader has already been exposed to RNNs and LSTM networks through numerous available resources and is open to an alternative pedagogical approach. A Machine Learning practitioner seeking guidance for implementing our new augmented LSTM model in software for experimentation and research will find the insights and derivations in this tutorial valuable as well.Comment: 43 pages, 10 figures, 78 reference