A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Prediction of psychoticlike symptoms in hypothetically psychosis-prone college students.

Correlates of psychotic and psychoticlike symptoms were examined in 60 college students who scored deviantly high on the Perceptual Aberration Scale. High scorers on this scale who also scored high on both the Impulsive Nonconformity Scale and the Depression subscale of the General Behavior Inventory (GBI) showed the most deviant psychotic and psychoticlike symptoms. Moreover, performance on a task of referential communication, the Password Task, was significantly related to such symptoms. The Perceptual Aberration Scale, the Impulsive Nonconformity Scale, and the GBI Depression subscale are recommended for concurrent use in mass screening to select individuals likely to exhibit psychotic or psychoticlike symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decision support for Cybersecurity risk planning

Security countermeasures help ensure the confidentiality, availability, and integrity of information systems by preventing or mitigating asset losses from Cybersecurity attacks. Due to uncertainty, the financial impact of threats attacking assets is often difficult to measure quantitatively, and thus it is difficult to prescribe which countermeasures to employ. In this research, we describe a decision support system for calculating the uncertain risk faced by an organization under cyber attack as a function of uncertain threat rates, countermeasure costs, and impacts on its assets. The system uses a genetic algorithm to search for the best combination of countermeasures, allowing the user to determine the preferred tradeoff between the cost of the portfolio and resulting risk. Data collected from manufacturing firms provide an example of results under realistic input conditions.     

Experimentation and the evaluation of energy efficiency programs

The use of experiments— particularly randomized controlled trials (RCTs) where subjects are randomly assigned to treatment and control conditions—has rarely been applied to the process of improving the design of energy efficiency programs and, more fundamentally, to determining the net savings from energy efficiency programs. This paper discusses the use of experimentation in the energy efficiency program field with the hope of explaining how these experiments can be used, and identifying the barriers to their use will cause more experimentation to occur. First, a brief overview of experimental methods is presented. This discussion describes the advantages and disadvantages of conducting experiments in the context of the development and evaluation of energy efficiency programs. It then discusses barriers to the use of experimental methods (including cost and equity issues) and suggests some ways of overcoming these barriers. Finally, recommendations are made for implementing key social experiments, discussing the types of energy efficiency programs and issues that can make use of experimentation and variables that one might use for selecting treatments.     

Effectual dispersion of carbon nanofibers in polyetherimide composites and their mechanical and tribological properties

The use of proliferation of nanotechnology in commercial applications is driving requirements for minimal chemical processing and simple processes in industry. Carbon nanofiber (CNF) products possess very high purity levels without the need of purification processing before use and are in growing demand for this quality. Polyetherimide (PEI) has excellent mechanical and thermal performance, but its high viscosity makes its nanocomposites processing very challenging. In this study, a facile melt‐mixing method was used to fabricate PEI nanocomposites with as received and physically treated CNFs. The dispersion of CNFs was characterized by scanning electron microscopy, transmitted optical microscopy, and electrometer with large‐area electrodes. The results showed that the facile and powerful melt‐mixing method is effective in homogeneously dispersing CNFs in the PEI matrix. The flexural and tribological characteristics were investigated and the formation of spatial networks of CNFs and weak interfacial bonding were considered as competitive factors to enhanced flexural properties. The composites with 1.0 wt% CNFs showed flexural strength and toughness increased by more than 50 and 550%, respectively, but showed very high wear rate comparable with that of pure PEI. The length of the CNFs also exerted great influences on both mechanical and tribological behaviors. POLYM. ENG. SCI., 50:1914–1922, 2010. © 2010 Society of Plastics Engineers     

Force-Commutated Reactive-Power Compensator

A reactive-power compensator (RPC) is a type of static var compensator (SVC) that is used to dynamically correct power factor to prevent voltage variation (flicker) in ac power sources due to large dynamic loads. It also minimizes total source current. Thus the application of an RPC or SVC to a load may allow addition of substantial new load to existing feeders or substations. A reactive-power compensator suited to industrial ratings (1.0-25 MVA) is described. It utilizes a force-commutated current-source bridge to provide both leading and lagging reactive power. The ability to operate both leading and lagging can reduce by 2:1 the ratings of the RPC itself and the capacitors and magnetics associated with it. The characteristics of the power circuit, the means used to control it, and the resulting dynamic performance is described. Speed of response compares favorably to the thyristor-controlled reactors now in common use as SVC's at higher MVA ratings. This RPC is suited to compensate any balanced three-phase dynamic load.     

Design and Control Techniques for Extending High Frequency Operation of a CSI Induction Motor Drive

An investigation of the maximum speed capability of a current source inverter (CSI) drive in both a three-and a six-phase connection is presented. It is shown that a six-phase configuration has distinct advantages over a three-phase connection in high speed capability for the same peak motor spike voltages. In addition, with proper control of the firing pulses fed to the inverters supplying the six-phase machine, the speed range can be substantially extended beyond the maximum limit predicted using conventional control. Predicted analytical results are correlated with results obtained by a detailed hybrid computer simulation.     

Monaural and binaural story recall by schizophrenic subjects.

P. Green and other investigators have reported that schizophrenic Ss have poorer recall of stories presented to both ears than to the single best ear (binaural deficit) and poorer recall of stories presented to the left ear than to the right ear (monaural asymmetry) than do normal control Ss. These studies are plagued by potential methodological problems, including differences in overall accuracy, which artifactually affect the difference scores, and scoring methods that are vulnerable to systematic bias. In this study, scores of schizophrenic, bipolar, and normal control Ss on the Auditory Comprehension Test were compared. Scoring bias was avoided by the use of blind scoring and a revised scoring manual, and artifactual effects of accuracy were considered in interpreting the results. Contrary to previous findings, the groups did not differ on either monaural asymmetry or binaural deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)