519 research outputs found

    Foundation Payout Increase Policy

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    The endowment payout rate of private foundations for charitable purposes has been 5% since last established in the Economic Recovery Tax Act of 1981. Despite other tax policies having been reassessed in that time, this portion of the tax code has been untouched for almost 30 years, during which the needs of the nonprofit sector have changed drastically. A small number of private foundations have increased their payout rate to give more immediate funding to the organizations that they support, but the vast majority give at or near the minimum 5% required. This policy recommends increasing the private foundation payout rate from 5% to 8% to account for higher indirect costs at nonprofits and the immediacy of many societal issues. While this policy is modest in scope, for the nonprofit field, having a 3% increase in available annual charitable giving could have significant and lasting positive impact on the field

    Crater population and resurfacing of the Martian north polar layered deposits

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    Present-day accumulation in the north polar layered deposits (NPLD) is thought to occur via deposition on the north polar residual cap. Understanding current mass balance in relation to current climate would provide insight into the climatic record of the NPLD. To constrain processes and rates of NPLD resurfacing, a search for craters was conducted using images from the Mars Reconnaissance Orbiter Context Camera. One hundred thirty craters have been identified on the NPLD, 95 of which are located within a region defined to represent recent accumulation. High Resolution Imaging Science Experiment images of craters in this region reveal a morphological sequence of crater degradation that provides a qualitative understanding of processes involved in crater removal. A classification system for these craters was developed based on the amount of apparent degradation and infilling and where possible depth/diameter ratios were determined. The temporal and spatial distribution of crater degradation is interpreted to be close to uniform. Through comparison of the size-frequency distribution of these craters with the expected production function, the craters are interpreted to be an equilibrium population with a crater of diameter D meters having a lifetime of ~30.75D^(1.14) years. Accumulation rates within these craters are estimated at 7.2D^(−0.14) mm/yr, which corresponds to values of ~3–4 mm/yr and are much higher than rates thought to apply to the surrounding flat terrain. The current crater population is estimated to have accumulated in the last ~20 kyr or less

    Lowest eigenvalues of the Dirac operator for two color QCD at nonzero chemical potential

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    We investigate the eigenvalue spectrum of the staggered Dirac matrix in SU(3) and U(1) gauge theory as well as in full QCD with two colors and finite chemical potential. Along the strong-coupling axis up to the phase transition, the low-lying Dirac spectrum of these quantum field theories is well described by random matrix theory and exhibits universal behavior. Related results for gauge theories with minimal coupling are discussed in the chirally symmetric phase and no universality is seen for the microscopic spectral densities.Comment: Lattice2001(hightemp), 3 pages, 9 figure

    Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay.

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    Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes (EGFR, ERBB2 and MET)). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration (TP53). Ninety patients with non-brain tumors had a discernible aberration (65% of 138 patients; in 70% of non-brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent

    Systematic analysis of the DNA damage response network in telomere defective budding yeast

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    Functional telomeres are critically important to eukaryotic genetic stability. Scores of proteins and pathways are known to affect telomere function. Here, we report a series of related genome-wide genetic interaction screens performed on budding yeast cells with acute or chronic telomere defects. Genetic interactions were examined in cells defective in Cdc13 and Stn1, affecting two components of CST, a single stranded DNA (ssDNA) binding complex that binds telomeric DNA. For comparison, genetic interactions were also examined in cells with defects in Rfa3, affecting the major ssDNA binding protein, RPA, which has overlapping functions with CST at telomeres. In more complex experiments, genetic interactions were measured in cells lacking EXO1 or RAD9, affecting different aspects of the DNA damage response, and containing a cdc13-1 induced telomere defect. Comparing fitness profiles across these data sets helps build a picture of the specific responses to different types of dysfunctional telomeres. The experiments show that each context reveals different genetic interactions, consistent with the idea that each genetic defect causes distinct molecular defects. To help others engage with the large volumes of data, the data are made available via two interactive web-based tools: Profilyzer and DIXY. One particularly striking genetic interaction observed was that the chk1∆ mutation improved fitness of cdc13-1 exo1∆ cells more than other checkpoint mutations (ddc1∆, rad9∆, rad17∆, and rad24∆), whereas, in cdc13-1 cells, the effects of all checkpoint mutations were similar. We show that this can be explained by Chk1 stimulating resection—a new function for Chk1 in the eukaryotic DNA damage response network

    The effect of opioid therapy on sleep quality in patients with chronic non-malignant pain : a systematic review and exploratory meta-analysis

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    Current guidelines recommend opioid therapy to chronic non-malignant pain (CNP) patients when the benefits for pain and function outweigh risks. This systematic review examined the effects of opioid therapy on sleep – a valued functional outcome– in CNP. Electronic and hand searches of relevant studies up through July 2017 identified 18 eligible studies providing data from 3,746 CNP patients for analysis. Twelve of these studies were randomised controlled trials (RCTs) of up to 12-month in duration. Low-medium dosed oxycodone and transdermal fentanyl were the most tested therapies (n=4 each). Only two studies used objective sleep measure in addition to self-report ratings, questionnaires or sleep diary. Whilst calmer sleep with less body/leg movements and fewer awakenings could be achieved following opioid therapy, these might occur with increased sleep-disordered breathing and a much-shortened rapid eye movement (REM) sleep latency. Both the narrative synthesis and exploratory meta-analysis suggest that opioid therapy in CNP is associated with improved self-reported sleep quality. However, the effect is inconsistent, small (Standardised Mean Difference = 0.36), and may be accompanied by excessive daytime sleepiness. As a Cochrane-recommended assessment revealed “unclear” or “high” overall risk of bias for all studies, future opioid trials of stronger methodology and better reporting are needed to confirm and elucidate the effect

    Neanderthal Extinction by Competitive Exclusion

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    International audienceBackground: Despite a long history of investigation, considerable debate revolves around whether Neanderthals became extinct because of climate change or competition with anatomically modern humans (AMH). Methodology/Principal Findings: We apply a new methodology integrating archaeological and chronological data with high-resolution paleoclimatic simulations to define eco-cultural niches associated with Neanderthal and AMH adaptive systems during alternating cold and mild phases of Marine Isotope Stage 3. Our results indicate that Neanderthals and AMH exploited similar niches, and may have continued to do so in the absence of contact. Conclusions/Significance: The southerly contraction of Neanderthal range in southwestern Europe during Greenland Interstadial 8 was not due to climate change or a change in adaptation, but rather concurrent AMH geographic expansion appears to have produced competition that led to Neanderthal extinction
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