Inverse Bremsstrahlung Stabilization of Noise in the Generation of Ultra-short Intense Pulses by Backward Raman Amplification

Inverse bremsstrahlung absorption of the pump laser beam in a backward Raman amplifier over the round-trip light transit time through the sub-critical density plasma can more than double the electron temperature of the plasma and produce time-varying axial temperature gradients. The resulting increased Landau damping of the plasma wave and detuning of the resonance can act to stabilize the pump against unwanted amplification of Langmuir noise without disrupting nonlinear amplification of the femtosecond seed pulse. Because the heating rate increases with the charge state Z, only low-Z plasmas (hydrogen, helium, or helium-hydrogen mixtures) will maintain a low enough temperature for efficient operation

Regional and global forcing of glacier retreat during the last deglaciation

The ongoing retreat of glaciers globally is one of the clearest manifestations of recent global warming associated with rising greenhouse gas concentrations. By comparison, the importance of greenhouse gases in driving glacier retreat during the most recent deglaciation, the last major interval of global warming, is unclear due to uncertainties in the timing of retreat around the world. Here we use recently improved cosmogenic-nuclide production-rate calibrations to recalculate the ages of 1,116 glacial boulders from 195 moraines that provide broad coverage of retreat in mid-to-low-latitude regions. This revised history, in conjunction with transient climate model simulations, suggests that while several regional-scale forcings, including insolation, ice sheets and ocean circulation, modulated glacier responses regionally, they are unable to account for global-scale retreat, which is most likely related to increasing greenhouse gas concentrations.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at: http://www.nature.com/ncomms/2015/150821/ncomms9059/full/ncomms9059.htm

Relative Effectiveness of Mating Success and Sperm Competition at Eliminating Deleterious Mutations in Drosophila melanogaster

Condition-dependence theory predicts that sexual selection will facilitate adaptation by selecting against deleterious mutations that affect the expression of sexually selected traits indirectly via condition. Recent empirical studies have provided support for this prediction; however, their results do not elucidate the relative effects of pre- and postcopulatory sexual selection on deleterious mutations. We used the Drosophila melanogaster model system to discern the relative contributions of pre- and postcopulatory processes to selection against deleterious mutations. To assess second-male ejaculate competition success (P2; measured as the proportion of offspring attributable to the experimental male) and mating success, mutant and wild-type male D. melanogaster were given the opportunity to mate with females that were previously mated to a standard competitor male. This process was repeated for males subjected to a diet quality manipulation to test for effects of environmentally-manipulated condition on P2 and mating success. While none of the tested mutations affected P2, there was a clear effect of condition. Conversely, several of the mutations affected mating success, while condition showed no effect. Our results suggest that precopulatory selection may be more effective than postcopulatory selection at removing deleterious mutations. The opposite result obtained for our diet manipulation points to an interesting discrepancy between environmental and genetic manipulations of condition, which may be explained by the multidimensionality of condition. Establishing whether the various stages of sexual selection affect deleterious mutations differently, and to what extent, remains an important issue to resolve

A Randomized Placebo-Controlled Trial of \u3cem\u3eN\u3c/em\u3e-Acetylcysteine for Cannabis Use Disorder in Adults

Background—Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. Methods—In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. Results—There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio = 1.00, 95% confidence interval 0.63 – 1.59; p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. Conclusions—In contrast with prior findings in adolescents, there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors

Spatiotemporal Patterns in Nest Box Occupancy by Tree Swallows Across North America

Data from the North American Breeding Bird Survey (BBS) suggest that populations of aerial insectivorous birds are declining, particularly in northeastern regions of the continent, and particularly since the mid-1980s. Species that use nest boxes, such as Tree Swallows (Tachycineta bicolor), may provide researchers with large data sets that better reveal finer-scale geographical patterns in population trends. We analyzed trends in occupancy rates for ca. 40,000 Tree Swallow nest-box-years from 16 sites across North America. The earliest site has been studied intensively since 1969 and the latest site since 2004. Nest box occupancy rates declined significantly at five of six (83%) sites east of -78° W longitude, whereas occupancy rates increased significantly at four of ten sites (40%) west of -78° W longitude. Decreasing box occupancy trends from the northeast were broadly consistent with aspects of a previous analysis of BBS data for Tree Swallows, but our finding of instances of increases in other parts of the continent are novel. Several questions remain, particularly with respect to causes of these broad-scale geographic changes in population densities of Tree Swallows. The broad geographic patterns are consistent with a hypothesis of widespread changes in climate on wintering, migratory, or breeding areas that in turn may differentially affect populations of aerial insects, but other explanations are possible. It is also unclear whether these changes in occupancy rates reflect an increase or decrease in overall populations of Tree Swallows. Regardless, important conservation steps will be to unravel causes of changing populations of aerial insectivores in North America

The Combination of BH3-Mimetic ABT-737 with the Alkylating Agent Temozolomide Induces Strong Synergistic Killing of Melanoma Cells Independent of p53

Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ) is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2 family members, has been found to enhance the efficacy of many conventional chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT-737 induced strong synergistic apoptosis in multiple human melanoma cell lines. When the drugs were used in combination in a mouse xenograft model, they drastically reduced tumor growth at concentrations where each individual drug had no significant effect. We found that TMZ treatment elevated p53 levels, and that the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells. Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT-737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer, demonstrated that p53 induction was sufficient for synergistic cell death with ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT-737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737 together induce Noxa in a p53-independent fashion. These results demonstrate that targeting anti-apoptotic Bcl-2 members is a promising method for treating metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are warranted

Coevolution of Interacting Fertilization Proteins

Reproductive proteins are among the fastest evolving in the proteome, often due to the consequences of positive selection, and their rapid evolution is frequently attributed to a coevolutionary process between interacting female and male proteins. Such a process could leave characteristic signatures at coevolving genes. One signature of coevolution, predicted by sexual selection theory, is an association of alleles between the two genes. Another predicted signature is a correlation of evolutionary rates during divergence due to compensatory evolution. We studied female–male coevolution in the abalone by resequencing sperm lysin and its interacting egg coat protein, VERL, in populations of two species. As predicted, we found intergenic linkage disequilibrium between lysin and VERL, despite our demonstration that they are not physically linked. This finding supports a central prediction of sexual selection using actual genotypes, that of an association between a male trait and its female preference locus. We also created a novel likelihood method to show that lysin and VERL have experienced correlated rates of evolution. These two signatures of coevolution can provide statistical rigor to hypotheses of coevolution and could be exploited for identifying coevolving proteins a priori. We also present polymorphism-based evidence for positive selection and implicate recent selective events at the specific structural regions of lysin and VERL responsible for their species-specific interaction. Finally, we observed deep subdivision between VERL alleles in one species, which matches a theoretical prediction of sexual conflict. Thus, abalone fertilization proteins illustrate how coevolution can lead to reproductive barriers and potentially drive speciation

Genome modeling system: A knowledge management platform for genomics

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms

Calpains Mediate Integrin Attachment Complex Maintenance of Adult Muscle in Caenorhabditis elegans

Two components of integrin containing attachment complexes, UNC-97/PINCH and UNC-112/MIG-2/Kindlin-2, were recently identified as negative regulators of muscle protein degradation and as having decreased mRNA levels in response to spaceflight. Integrin complexes transmit force between the inside and outside of muscle cells and signal changes in muscle size in response to force and, perhaps, disuse. We therefore investigated the effects of acute decreases in expression of the genes encoding these multi-protein complexes. We find that in fully developed adult Caenorhabditis elegans muscle, RNAi against genes encoding core, and peripheral, members of these complexes induces protein degradation, myofibrillar and mitochondrial dystrophies, and a movement defect. Genetic disruption of Z-line– or M-line–specific complex members is sufficient to induce these defects. We confirmed that defects occur in temperature-sensitive mutants for two of the genes: unc-52, which encodes the extra-cellular ligand Perlecan, and unc-112, which encodes the intracellular component Kindlin-2. These results demonstrate that integrin containing attachment complexes, as a whole, are required for proper maintenance of adult muscle. These defects, and collapse of arrayed attachment complexes into ball like structures, are blocked when DIM-1 levels are reduced. Degradation is also blocked by RNAi or drugs targeting calpains, implying that disruption of integrin containing complexes results in calpain activation. In wild-type animals, either during development or in adults, RNAi against calpain genes results in integrin muscle attachment disruptions and consequent sub-cellular defects. These results demonstrate that calpains are required for proper assembly and maintenance of integrin attachment complexes. Taken together our data provide in vivo evidence that a calpain-based molecular repair mechanism exists for dealing with attachment complex disruption in adult muscle. Since C. elegans lacks satellite cells, this mechanism is intrinsic to the muscles and raises the question if such a mechanism also exists in higher metazoans

SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States

This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe