803 research outputs found

    Improving School Accountability in California

    Get PDF
    Proposes a value-added model for assessing schools that measures contributions to student learning based on whether average test scores are higher or lower than expected, given prior achievement and other characteristics. Outlines implementation issues

    Analytical Investigation of the Reentry Behavior of the ''flying Wind Tunnel'' Test Vehicle, with Some Effects of Threshold and Torque Level of a Roll-rate Control System

    Get PDF
    Analytical investigation of reentry behavior of flying wind tunnel test vehicle with some effects of threshold and torque level of roll-rate control syste

    Fractal-like structures in colloid science

    Get PDF
    The present work aims at reviewing our current understanding of fractal structures in the frame of colloid aggregation as well as the possibility they offer to produce novel structured materials. In particular, the existing techniques to measure and compute the fractal dimension df are critically discussed based on the cases of organic/inorganic particles and proteins. Then the aggregation conditions affecting df are thoroughly analyzed, pointing out the most recent literature findings and the limitations of our current understanding. Finally, the importance of the fractal dimension in applications is discussed along with possible directions for the production of new structured materials

    The action of physiological and synthetic steroids on the calcium channel CatSper in human sperm

    Get PDF
    The sperm-specific channel CatSper (cation channel of sperm) controls the intracellular Ca2+ concentration ([Ca2+]i) and plays an essential role in sperm function. It is mainly activated by the steroid progesterone (P4) but is also promiscuously activated by a wide range of synthetic and physiological compounds. These compounds include diverse steroids whose action on the channel is so far still controversial. To investigate the effect of these compounds on CatSper and sperm function, we developed a high-throughput screening (HTS) assay to measure changes in [Ca2+]i in human sperm and screened 1,280 approved and off-patent drugs including 90 steroids from the Prestwick chemical library. More than half of the steroids tested (53%) induced an increase in [Ca2+]i and reduced the P4-induced Ca2+ influx in human sperm in a dose-dependent manner. Ten of the most potent steroids (activating and P4-inhibiting) were selected for a detailed analysis of their action on CatSper and their ability to act on sperm acrosome reaction (AR) and penetration in viscous media. We found that these steroids show an inhibitory effect on P4 but not on prostaglandin E1-induced CatSper activation, suggesting that they compete for the same binding site as P4. Pregnenolone, dydrogesterone, epiandrosterone, nandrolone, and dehydroepiandrosterone acetate (DHEA) were found to activate CatSper at physiologically relevant concentrations within the nanomolar range. Like P4, most tested steroids did not significantly affect the AR while stanozolol and estropipate slightly increased sperm penetration into viscous medium. Furthermore, using a hybrid approach integrating pharmacophore analysis and statistical modelling, we were able to screen in silico for steroids that can activate the channel and define the physicochemical and structural properties required for a steroid to exhibit agonist activity against CatSper. Overall, our results indicate that not only physiological but also synthetic steroids can modulate the activity of CatSper with varying potency and if bound to CatSper prior to P4, could impair the timely CatSper activation necessary for proper fertilization to occur

    Global regulatory architecture of human, mouse and rat tissue transcriptomes

    Get PDF
    Background Predicting molecular responses in human by extrapolating results from model organisms requires a precise understanding of the architecture and regulation of biological mechanisms across species. Results Here, we present a large-scale comparative analysis of organ and tissue transcriptomes involving the three mammalian species human, mouse and rat. To this end, we created a unique, highly standardized compendium of tissue expression. Representative tissue specific datasets were aggregated from more than 33,900 Affymetrix expression microarrays. For each organism, we created two expression datasets covering over 55 distinct tissue types with curated data from two independent microarray platforms. Principal component analysis (PCA) revealed that the tissue-specific architecture of transcriptomes is highly conserved between human, mouse and rat. Moreover, tissues with related biological function clustered tightly together, even if the underlying data originated from different labs and experimental settings. Overall, the expression variance caused by tissue type was approximately 10 times higher than the variance caused by perturbations or diseases, except for a subset of cancers and chemicals. Pairs of gene orthologs exhibited higher expression correlation between mouse and rat than with human. Finally, we show evidence that tissue expression profiles, if combined with sequence similarity, can improve the correct assignment of functionally related homologs across species. Conclusion The results demonstrate that tissue-specific regulation is the main determinant of transcriptome composition and is highly conserved across mammalian species
    • …
    corecore