Previous Experimental Evaluation Research Articles

In-depth analysis of Gαs protein activity by probing different fluorescently labeled guanine nucleotides.

G proteins are interacting partners of G protein-coupled receptors (GPCRs) in eukaryotic cells. Upon G protein activation, the ability of the Gα subunit to exchange GDP for GTP determines the intracellular signal transduction. Although various studies have successfully shown that both Gαs and Gαi have an opposite effect on the intracellular cAMP production, with the latter being commonly described as "more active", the functional analysis of Gαs is a comparably more complicated matter. Additionally, the thorough investigation of the ubiquitously expressed variants of Gαs, Gαs(short) and Gαs(long), is still pending. Since the previous experimental evaluation of the activity and function of the Gαs isoforms is not consistent, the focus was laid on structural investigations to understand the GTPase activity. Herein, we examined recombinant human Gαs by applying an established methodological setup developed for Gαi characterization. The ability for GTP binding was evaluated with fluorescence and fluorescence anisotropy assays, whereas the intrinsic hydrolytic activity of the isoforms was determined by a GTPase assay. Among different nucleotide probes, BODIPY FL GTPγS exhibited the highest binding affinity towards the Gαs subunit. This work provides a deeper understanding of the Gαs subunit and provides novel information concerning the differences between the two protein variants.

ParRADMeth: Identification of Differentially Methylated Regions on Multicore Clusters.

The discovery of Differentially Methylated (DM) regions is an important research field in biology, as it can help to anticipate the risk of suffering from specific diseases. Nevertheless, the high computational cost of the bioinformatic tools developed for this purpose prevents their application to large-scale datasets. Hence, much faster tools are required to further progress in this research field. In this work we present ParRADMeth, a parallel tool that applies beta-binomial regression for the identification of these DM regions. It is based on the state-of-the-art sequential tool RADMeth, which proved superior biological accuracy compared to counterparts in previous experimental evaluations. ParRADMeth provides the same DM regions as RADMeth but at significantly reduced runtime thanks to exploiting the compute capabilities of common multicore CPU clusters. For example, our tool is up to 189 times faster for real data experiments on a cluster with 16 nodes, each one containing two eight-core processors. The source code of ParRADMeth, as well as a reference manual, are available at https://github.com/UDC-GAC/ParRADMeth.

PRIblast: A highly efficient parallel application for comprehensive lncRNA–RNA interaction prediction

Long non-coding RNAs (lncRNAs) play a key role in several biological processes and scientists are constantly trying to come up with new strategies to elucidate their functions. One common approach to characterize these sequences consists in predicting their interactions with other RNA fragments. Nevertheless, the high computational cost of the bioinformatics tools developed for this purpose prevents their application to large-scale datasets. This paper presents pRIblast, a highly efficient parallel application for comprehensive lncRNA–RNA interaction prediction based on the state-of-the-art RIblast tool, which has been proved to show superior biological accuracy compared to other counterparts in previous experimental evaluations. Benchmarking on a multicore CPU cluster shows that pRIblast is able to compute in a few hours analyses that would need more than three months to complete with the original RIblast algorithm, always achieving the same level of prediction accuracy. Furthermore, this novel application can process large input datasets that cannot be processed with the former tool. pRIblast is free software publicly available to download at https://github.com/UDC-GAC/pRIblast under the MIT license.

Evaluating the My Life self-determination model for older youth in foster care: Establishing efficacy and exploring moderation of response to intervention

Limited rigorous research has been conducted to evaluate the impact of interventions designed to promote the successful transitions of young people exiting foster care. The current study builds on previous experimental evaluations of the My Life Model (MLM) for self-determination enhancement, which demonstrated effectiveness in improving educational and transition-to-adulthood outcomes for youth in foster care with disabilities, including those with mental health challenges. The model features one-on-one youth-directed coaching and near-peer mentoring to increase self-determination and goal achievement. The current study was the first to test the impact of the model with a diverse population-based cohort of youth aged 16.5-18.5 in foster care (N=293), including those with and without disabilities, on key model outcome indicators of self-determination and self-efficacy. This study also explored potential moderation by disability status, trauma symptoms, placement stability, and placement restrictiveness. Findings show that, compared to the randomized control group, the treatment group had greater post-intervention and one-year follow-up gains on several indicators of self-determination. Moderation analysis demonstrated no difference in intervention effectiveness for youth with or without disabilities, suggesting the universality of this approach. Findings also suggest that foster youth participants with low-to-average risks in terms of placement stability, placement restrictiveness, and traumatic stress levels seem to benefit most from the intervention, although youth who are at higher risk due to low placement stability, high placement restriction, and high traumatic stress still showed some benefit of participating in the intervention on some measures. My Life is one of only a few intervention models with experimental evidence of effectiveness with older youth in foster care. This validation study establishes that the approach has benefits for both youth with and without disabilities, as well as providing the first information available on the influence of critical barriers facing many youth in care.

2‐Mercapto Benzthiazole Coupled Benzyl Triazoles as New COX‐2 Inhibitors: Design, Synthesis, Biological Testing and Molecular Modeling Studies

AbstractA series of 2‐mercapto benzothiazole linked with triazoles (3 a‐u) were designed based on our previous experimental evaluation of benzothiazole allied oxadiazoles and synthesized in two step starting from the 2‐mercaptan precursor. The structure of the benzothiazoles were confirmed by infrared (IR), nuclear magnetic resonance (NMR) and mass (LC–MS) spectral data. The insilico binding mode interpretations in both COX‐1/COX‐2 was investigated, their probable binding energies were predicted and ADMET properties were calculated. The molecular level interactions of the designed library indicated, the aryl ring united with triazole was occupying as mefenamic acid in COX‐2 active site. All the benzothiazoles 3 a‐u were evaluated for their COX inhibitory activities as per the standard protocol reported elsewhere. 2‐(((1‐(2‐chlorobenzyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)benzo[d]thiazole 3 i, 4‐((4‐((benzo[d]thiazol‐2‐ylthio)methyl)‐1H‐1,2,3‐triazol‐1‐yl)methyl)benzoic acid 3 t and 4‐((4‐((benzo[d]thiazol‐2‐ylthio)methyl)‐1H‐1,2,3‐triazol‐1‐yl)methyl)benzamide 3 u based benzthiazoles showed the most significant COX‐2 inhibitory activity with an IC50 of 4.1, 4.3 and 5.4 μM respectively. The time dependant increase in inhibition of inflammation of above COX‐2 inhibitors in invivo anti‐inflammatory evaluation was noticed. Additionally, 2‐(((1‐(3‐fluorobenzyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)benzo[d]thiazole 3 g expressed the significant DPPH scavenging activity with 80.45 percent inhibition at 100 μM and an IC50 of 27.8 μM. Furthermore, the 50 ns molecular dynamic simulations of 2‐(((1‐(2‐chlorobenzyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)benzo[d]thiazole 3 i to interpret the constant residue interactions might liable for the COX selectivity was presented. Later, they also have been tested for cancer lines at NCI and obtained data were provided.

Engineering Methods for Differentially Private Histograms: Efficiency Beyond Utility

Publishing histograms with $\epsilon$ - differential privacy has been studied extensively in the literature. Existing schemes aim at maximizing the utility of the published data, while previous experimental evaluations analyze the privacy/utility trade-off. In this paper, we provide the first experimental evaluation of differentially private methods that goes beyond utility, emphasizing also on another important aspect, namely efficiency . Towards this end, we first observe that all existing schemes are comprised of a small set of common blocks. We then optimize and choose the best implementation for each block, determine the combinations of blocks that capture the entire literature, and propose novel block combinations. We qualitatively assess the quality of the schemes based on the skyline of efficiency and utility, i.e., based on whether a method is dominated on both aspects or not. Using exhaustive experiments on four real datasets with different characteristics, we conclude that there are always trade-offs in terms of utility and efficiency. We demonstrate that the schemes derived from our novel block combinations provide the best trade-offs for time critical applications. Our work can serve as a guide to help practitioners engineer a differentially private histogram scheme depending on their application requirements.

A Wire-Bondless Packaging Platform for Silicon Carbide Power Semiconductor Devices

As silicon carbide (SiC) power semiconductor devices continue to mature for market adoption, innovative power electronics packaging designs and materials are needed. Wire-bonding loop is one of the limiting factors in traditional module packaging methods. Wire-bondless packaging methods have been demonstrated with low losses and to allow integration of gate drive circuit. In this paper, a wire-bondless packaging platform, referred to as power overlay kiloWatt (POL-kW), for SiC devices is presented. The packaging platform is intended for motor drives and power conversion in automotive, aerospace, and renewable power applications. POL-kW module's electrical and thermal performances are first summarized from previous experimental evaluations and numerical simulations. Although some of the evaluations were made using Si and Si–SiC hybrid modules, the results are applicable to SiC modules. Compared with aluminum wire-bonds, the utilization of polyimide-based Cu via interconnections resulted in much reduced parasitic inductance, contributing to significantly lower switching loss and less voltage overshoot. The POL-kW module with integrated heat sinks showed low thermal resistance, which was further reduced by double-sided cooling. Recent reliability results are presented, including high-temperature storage, temperature cycling, and power cycling.

Optimization of rapid acquisition with relaxation enhancement (RARE) pulse sequence parameters for ¹⁹F-MRI studies.

To optimize signal-to-noise ratio (SNR) in fast spin echo (rapid acquisition with relaxation enhancement [RARE]) sequences and to improve sensitivity in ¹⁹F magnetic resonance imaging (MRI) on a 7T preclinical MRI system, based on a previous experimental evaluation of T₁ and T₂ actual relaxation times. Relative SNR changes were theoretically calculated at given relaxation times (T₁, T₂) and mapped in RARE parameter space (TR, number of echoes, flip back pulse), at fixed acquisition times. T₁ and T₂ of KPF₆ phantom samples (solution, agar mixtures, ex vivo perfused brain) were measured and experimental SNR values were compared with simulations, at optimal and suboptimal RARE parameter values. The optimized setting largely depended on T₁, T₂ times and the use of flip back pulse improved SNR up to 30% in case of low T₁/T₂ ratios. Relaxation times in different conditions showed negligible changes in T₁ (below 14%) and more evident changes in T₂ (-95% from water solution to ex vivo brain). Experimental data confirmed theoretical forecasts, within an error margin always below 4.1% at SNR losses of ~20% and below 8.8% at SNR losses of ~40%. The optimized settings permitted a detection threshold at a concentration of 0.5 mM, corresponding to 6.22 × 10¹⁶ fluorine atoms per voxel. Optimal settings according to measured relaxation times can significantly improve the sensitivity threshold in ¹⁹F MRI studies. They were provided in a wide range of (T₁, T₂) values and experimentally validated showing good agreement.

Voxel-wise information theoretic EEG-fMRI feature integration

We have recently proposed the evaluation of a set of information theoretic quantities (ITQs) for the integration of simultaneously acquired EEG-fMRI data (Ostwald, D., Porcaro, C., Bagshaw, A.P., 2010. An information theoretic approach to EEG-fMRI integration of visually evoked responses. Neuroimage. 49, 498–516). In our previous experimental evaluation of the information theoretic framework, we defined the data subsets from which to calculate the ITQs using a priori constraints. In the case of EEG, this meant that data were extracted from a single electrode, while for fMRI the analysed data came from voxels contained within a sphere surrounding the most responsive voxel of visual cortex. While this approach was a natural starting point for the evaluation of the framework in the application to combined EEG–fMRI data sets, a more principled approach to data selection is desirable. Here, we propose to combine standard fMRI data pre-processing and low-resolution electromagnetic tomography (LORETA) for the evaluation of ITQs across the entire three-dimensional brain space. We apply the proposed method to a simultaneous EEG–fMRI data set acquired during checkerboard stimulation and assess the topographical informativeness of EEG (time and frequency domain) and fMRI features with respect to the stimulus and each other. The resulting information theoretic effect size maps are supplemented with a statistical evaluation based on Gaussian null model simulations using a false-discovery rate procedure. Given the contamination of EEG recordings by artefacts induced by the MR scanning environment we further assessed the influence of different advanced EEG pre-processing methods (independent component analysis and functional source separation) on the information topography. The results of this analysis provide evidence for the topographically focussed informativeness of both EEG and fMRI features with respect to the stimulus, but for the current feature selection do not detect EEG–fMRI activity dependence. More advanced EEG data pre-processing rendered the feature distributions more stimulus-informative, but did not alter the EEG–fMRI activity and conditional dependencies.

Do invasive cane toads (Chaunus marinus) compete with Australian frogs (Cyclorana australis)?

Abstract  Despite widespread concern about the ecological impacts of invasive species, mechanisms of impact remain poorly understood. Cane toads (Chaunus [Bufo] marinus) were introduced to Queensland in 1935, and have now spread across much of tropical Australia. One plausible impact of toad invasion concerns competition between toads and native frogs, but there has been no previous experimental evaluation of this possibility. We examined interactions between toads and a morphologically similar species of native frog (Cyclorana australis) by manipulating toad and frog densities within large outdoor enclosures beside a floodplain in the wet‐dry tropics of the Northern Territory. Toads differed from frogs significantly in dietary composition and feeding rates, even in comparisons controlling for body‐size differences between these two taxa. Perhaps reflecting the abundant insect biomass, manipulating anuran densities or the presence of the putatively competing species did not influence food intake or dietary composition. However, the presence of toads suppressed activity levels of native frogs. The degree to which the invasion of cane toads influences attributes such as the activity levels, food intake and dietary composition of native frogs warrants further study, but our study suggests that competitive effects are likely to be minor compared with other pathways (such as direct poisoning during ingestion attempts) by which toads can affect frog populations.

Community Programs to Promote Youth Development

Children, Youth and Environments Vol. 15 No. 2 (2005) ISSN: 1546-2250 Community Programs to Promote Youth Development Eccles, Jacquelynne and Gootman, Jennifer Appleton (2002). National Academy Press; 441 pages. $49.95. ISBN 0309072751. This book was written as the culminating work of the U.S.based National Research Council’s (NRC) and the Institute of Medicine’s (IOM) Committee on Community-Level Programs for Youth. The NRC and IOM Committee includes some of the best social scientists in the fields of adolescent development from such disciplines as: anthropology, education, human development and family studies, medicine, psychology, and sociology. It was published by the premier scientific publisher in the United States, the National Academy Press, and delineates what the United States social scientific community knows about youth development and contexts that foster the positive development of adolescents. The information it presents is useful for anyone who works with, studies, or advocates on behalf of youth, including practitioners and social scientists. 452 This book has importance for validating the youth development field. First, the involvement of two of the most prestigious research and scientific organizations in the United States, namely NRC and IOM, emphasizes the importance of youth development and community-based programming. Second, the multi-disciplinary nature of the committee which assisted Eccles and Gootman in synthesizing the research about effective practice and programming for youth development assured that the information is the most current and the best of what is known from a cluster of related fields. Third, the information is a concrete example of how science and practice are intertwined, informing each other through an iterative process. Thus, the information in this book is drawn from scientifically respected and historically significant research about adolescence and presented through the lens of practical application in order to improve practice within the youth work field. Community Programs to Promote Youth Development addresses five major points. First, it captures what social scientists know about adolescent development. Second, it elaborates the defining features of contexts (e.g., neighborhood, school, community-based program) that promote positive development in adolescence. Third, this book comprehensively identifies the varied landscape of communitybased youth programs. Fourth, it highlights lessons from experimental evaluations, directions for future evaluations, and potential new social indicator data. Finally, it concludes with clear recommendations for scientists, practitioners, funders, advocates, and policy-makers. The book is comprised of four sections. The first is a comprehensive literature review about adolescent development and positive developmental settings. The second section examines what is known about community programs for youth from research and evaluation studies. The third section provides information about directions for new research, including examination of potential existing data sources and the development of positive indicators. The fourth and final 453 chapter addresses the intersection of practice, research, and policy. Community Programs to Promote Youth Development summarizes what personal and social assets youth need to succeed. These assets are not directly associated with Search Institute’s 40 developmental assets (see Benson 1997). These assets fall into four broad developmental domains: physical, intellectual, psychological and emotional, and social. The assets were identified through a comprehensive scan of the literature on factors that increase the healthy development and well-being of youth in adolescence and as they transition into adulthood. The book discusses the interactions between and cumulative nature of these assets. For a practitioner, the book’s identification of specific features of positive developmental settings represents a road map to best practices in programming. These features include: physical and psychological safety; appropriate structure; supportive relationships; opportunities to belong; positive social norms; support for efficacy and mattering (opportunity to be useful and to make a difference); opportunities for skillbuilding (e.g., leadership skills, decision-making skills, cultural competence, communication skills, problem-solving skills, and civic responsibility); active learning; opportunities for recognition; and the integration of family, school, and community efforts. The book provides detailed explanations of these features as well as programmatic examples. The chapter on lessons drawn from previous experimental evaluations actually includes information from quasiexperimental designs as well because of the dearth of experimental studies available. One major recommendation by the book’s authors is that community-based programs should begin conducting experimental—or at least quasiexperimental...

Tandem repeat copy-number variation in protein-coding regions of human genes

Tandem repeat polymorphisms in human proteins were characterized using the UniGene dataset. This analysis suggests that 1 in 20 proteins are likely to contain tandem repeat copy-number polymorphisms within coding regions; these were prevalent among protein-binding proteins.

Evaluation of the Electrostatic Field Strength at the Site of Exocytosis in Adrenal Chromaffin Cells

Exocytosis in secretory cells consists of release from intracellular storage granules directly into the extracellular space via fusion of the granule membrane with the plasma membrane of the cell. It is considered here as comprising two distinct processes. One is the close apposition of granule and plasma membranes. The other arises from interactions between the two membranes during the process of apposition, leading to the formation of a fusion pore. In the following it is shown for the case of the adrenal medullary chromaffin cell that the fusion pore can be ascribed to electroporation of the granule membrane, triggered by the strong electric field existing at the site of exocytosis. Based on an electric surface charge model of the cytoplasmic side of the plasma membrane, resulting from the negatively charged phosphatidylserine groups, it is found that the electrostatic field strength at the site of exocytosis reaches values on the order of 10 8 V/m at small intermembrane distances of 3 nm and lower. The field strength increases with the size of the disc-shaped plasma membrane region generating the electric field, reaching an approximate limit for a radius of 10 nm, at a surface charge density of 5.4 × 10 −2 C/m 2. According to previous experimental evaluations of threshold field strength, this field is sufficiently strong to cause membrane electroporation. This step is a precondition for the subsequent membrane fusion during the ongoing process of apposition, leading to secretion.

A Review of Convective Loss Data From Solar Central Receivers

A summary of previous experimental evaluations to determine convective losses from solar central receivers is given. In this review studies performed directly on actual central receivers or simulations that closely approximate central receiver geometries are considered. Because of the diversity of the previous studies, there are a number of classifications of the studies that can be made. From one perspective, two types of evaluations have been carried out: either those using performance data (often called efficiency tests), or those configuring the receiver so that losses can be more directly inferred (loss tests). In addition to classifying the experimental configurations according to geometry type (either external or cavity forms), it is also beneficial to distinguish between evaluations that take place when normal solar flux levels are incident upon the receiver (flux-on tests) and those made with no flux present (flux-off evaluations). Previous tests are categorized according to the method of testing used. Special attention is given to the range of the physical parameters represented by the experiments, particularly the Grashof number. Too often sufficient information to characterize forced convection contributions is not available, but it is shown that the total convective loss sometimes is lower than the predictions for natural convection alone. It is shown that performance-based data does not correspond well with loss-based data. The effects of directional effects of forced convection and general aspects of mixed (natural and forced) convection are not well established in the existing data. There have been some flux-on techniques recommended recently that may overcome some of the previously established concerns about the accuracy of flux-on data.

Oscillatory Flow Birefringence of Polymer Molecules in Dilute Solutions

A theory for the behavior of dilute solutions of polymer molecules in oscillatory shear has been given by Zimm. Two variable parameters are contained in the theory, these being the number of statistical chain segments which are joined by bead joints and the degree of hydrodynamic interaction between the beads of the chain model. While previous experimental evaluations of the theory as applied to viscoelasticity have been restricted to the case of an infinite number of segments, the results obtained from oscillatory flow birefringence measurements show that a finite number of segments is essential to describing the behavior of the polymer. The analysis of birefringence measurements in terms of the Zimm theory yields values for the longest relaxation time τ1, the number of segments N, the reduction function aT, and the optical factor q′ characteristic of the subchain as well as the temperature dependence of the friction factor. Both oscillatory and steady-flow birefringence measurements for polystyrene S111 in Aroclor 1248 are compared with the theory for frequency and temperature dependence. For the solution tested, N lies between 40 and 100, τ1 is 0.00187 sec and the temperature dependence of the friction factor is approximately that of the solvent viscosity.