Processes controlling the seasonal variations of 210Pb and 7Be at the Mt. Cimone WMO-GAW global station, Italy: A model analysis

We apply the Global Modeling Initiative (GMI) chemistry and transport model 14 driven by the NASA\u2019s MERRA assimilated meteorological data to simulate the seasonal variations of two radionuclide aerosol tracers (terrigenous 210Pb and cosmogenic 7 15 Be) at the 16 WMO-GAW station of Mt. Cimone (44\ub012\u2019 N, 10\ub042\u2019 E, 2165 m asl, Italy), which is 17 representative of free-tropospheric conditions most of the year, during 2005 with an aim to 18 understand the roles of transport and precipitation scavenging processes in controlling their 19 seasonality. The total precipitation field in the MERRA data set is evaluated with the Global 20 Precipitation Climatology project (GPCP) observations, and a generally good agreement is found. The model reproduces reasonably the observed seasonal pattern of 210 21 Pb concentrations, characterized by a wintertime minimum due to lower 222 22 Rn emissions and weaker uplift from the boundary layer and summertime maxima resulting from strong convection over the continent. The observed seasonal behavior of 7Be concentrations shows a winter minimum, a summer maximum, and a secondary spring maximum. The model captures the observed 7Be 4 pattern in winter-spring, which is linked to the larger stratospheric influence during spring. However, the model tends to underestimate the observed 7Be concentrations in summer, 6 partially due to the sensitivity to spatial sampling in the model. Model sensitivity experiments 7 indicate a dominant role of precipitation scavenging (versus dry deposition and convection) in controlling the seasonality of 210Pb and 7 Be concentrations at Mt. Cimone

Sensitivity of Northern Hemisphere Cyclone Detection and Tracking Results to Fine Spatial and Temporal Resolution Using ERA5

Lagrangian detection and tracking algorithms are frequently used to study the development, distribution, and trends of extratropical cyclones. Past research shows that results from these algorithms are sensitive to both spatial and temporal resolution of the gridded input fields, with coarser resolutions typically underestimating cyclone frequency by failing to capture weak, small, and short-lived systems. The fifth-generation atmospheric reanalysis from the European Centre for Medium-Range Weather Forecasts (ERA5) offers finer resolution, and therefore more precise information regarding storm locations and development than previous global reanalyses. However, our sensitivity tests show that using ERA5 sea-level pressure fields at their finest possible resolution does not necessarily lead to better cyclone detection and tracking. If a common number of nearest neighbors is used when detecting minima in sea-level pressure (like past studies), finer spatial resolution leads to noisier fields that unrealistically break up multi-center cyclones. Using a common search distance instead (with more neighbors at finer resolution) resolves the issue without smoothing inputs. Doing this also makes cyclone frequency, lifespan, and average depth insensitive to refining spatial resolution beyond 100 km. Results using 6-h and 3-h temporal resolutions have only minor differences, but using 1-h temporal resolution with a maximum allowed propagation speed of 150 km h-1 leads to unrealistic track splitting. This can be counteracted by increasing the maximum propagation speed, but modest sensitivity to temporal resolution persists for several cyclone characteristics. Therefore, we recommend caution if applying existing algorithms to temporal resolutions finer than 3-h and careful evaluation of algorithm settings

The argument of the broken pane: Suffragette consumerism and newspapers

Within the cut-throat world of newspaper advertising the newspapers of Britain's Women's Social and Political Union (WSPU) Votes for Women and the Suffragette managed to achieve a balance that has often proved to be an impossible challenge for social movement press—namely the maintenance of a highly political stance whilst simultaneously exploiting the market system with advertising and merchandising. When the militant papers advocated window smashing of West End stores in 1912–1913, the companies who were the target still took advertisements. Why? What was the relationship between news values, militant violence and advertising income? ‘Do-it-yourself’ journalism operated within a context of ethical consumerism and promotionally orientated militancy. This resulted in newspaper connections between politics, commerce and a distinct market profile, evident in the customisation of advertising, retailer dialogue with militants and longer-term loyalty—symptomatic of a wider trend towards newspaper commercialism during this period

Cigarette brands with flavour capsules in the filter: Trends in use and brand perceptions among smokers in the USA, Mexico and Australia, 2012-2014

Objective To describe trends, correlates of use and consumer perceptions related to the product design innovation of flavour capsules in cigarette filters.  Methods Quarterly surveys from 2012 to 2014 were analysed from an online consumer panel of adult smokers aged 18–64, living in the USA (n=6865 observations; 4154 individuals); Mexico (n=5723 observations; 3366 individuals); and Australia (n=5864 observations; 2710 individuals). Preferred brand varieties were classified by price (ie, premium; discount) and flavour (ie, regular; flavoured without capsule; flavoured with capsule). Participants reported their preferred brand variety's appeal (ie, satisfaction; stylishness), taste (ie, smoothness, intensity), and harm relative to other brands and varieties. GEE models were used to determine time trends and correlates of flavour capsule use, as well as associations between preferred brand characteristics (ie, price stratum, flavour) and perceptions of relative appeal, taste and harm.  Results Preference for flavour capsules increased significantly in Mexico (6% to 14%) and Australia (1% to 3%), but not in the USA (4% to 5%). 18–24 year olds were most likely to prefer capsules in the USA (10%) and Australia (4%), but not Mexico. When compared to smokers who preferred regular brands, smokers who preferred brands with capsules viewed their variety of cigarettes as having more positive appeal (all countries), better taste (all countries), and lesser risk (Mexico, USA) than other brand varieties.  Conclusions Results indicate that use of cigarettes with flavour capsules is growing, is associated with misperceptions of relative harm, and differentiates brands in ways that justify regulatory action

The SRG Rat, a Sprague-Dawley Rag2/Il2rg Double-Knockout Validated for Human Tumor Oncology Studies

We have created the immunodeficient SRG rat, a Sprague-Dawley Rag2/Il2rg double knockout that lacks mature B cells, T cells, and circulating NK cells. This model has been tested and validated for use in oncology (SRG OncoRat®). The SRG rat demonstrates efficient tumor take rates and growth kinetics with different human cancer cell lines and PDXs. Although multiple immunodeficient rodent strains are available, some important human cancer cell lines exhibit poor tumor growth and high variability in those models. The VCaP prostate cancer model is one such cell line that engrafts unreliably and grows irregularly in existing models but displays over 90% engraftment rate in the SRG rat with uniform growth kinetics. Since rats can support much larger tumors than mice, the SRG rat is an attractive host for PDX establishment. Surgically resected NSCLC tissue from nine patients were implanted in SRG rats, seven of which engrafted and grew for an overall success rate of 78%. These developed into a large tumor volume, over 20,000 mm3 in the first passage, which would provide an ample source of tissue for characterization and/or subsequent passage into NSG mice for drug efficacy studies. Molecular characterization and histological analyses were performed for three PDX lines and showed high concordance between passages 1, 2 and 3 (P1, P2, P3), and the original patient sample. Our data suggest the SRG OncoRat is a valuable tool for establishing PDX banks and thus serves as an alternative to current PDX mouse models hindered by low engraftment rates, slow tumor growth kinetics, and multiple passages to develop adequate tissue banks

Fine-scale variability in coral bleaching and mortality during a marine heatwave

Coral bleaching and mortality can show significant spatial and taxonomic heterogeneity at local scales, highlighting the need to understand the fine-scale drivers and impacts of thermal stress. In this study, we used structure-from-motion photogrammetry to track coral bleaching, mortality, and changes in community composition during the 2019 marine heatwave in Kāneʻohe Bay, Hawaiʻi. We surveyed 30 shallow reef patches every 3 weeks for the duration of the bleaching event (August-December) and one year after, resulting in a total of 210 large-area, high-resolution photomosaics that enabled us to follow the fate of thousands of coral colonies through time. We also measured environmental variables such as temperature, sedimentation, depth, and wave velocity at each of these sites, and extracted estimates of habitat complexity (rugosity R and fractal dimension D) from digital elevation models to better understand their effects on patterns of bleaching and mortality. We found that up to 80% of corals experienced moderate to severe bleaching in this period, with peak bleaching occurring in October when heat stress (Degree Heating Weeks) reached its maximum. Mortality continued to accumulate as bleaching levels dropped, driving large declines in more heat-susceptible species (77% loss of Pocillopora cover) and moderate declines in heat-tolerant species (19% and 23% for Porites compressa and Montipora capitata, respectively). Declines in live coral were accompanied by a rapid increase in algal cover across the survey sites. Spatial differences in bleaching were significantly linked to habitat complexity and coral species composition, with reefs that were dominated by Pocillopora experiencing the most severe bleaching. Mortality was also influenced by species composition, fractal dimension, and site-level differences in thermal stress. Our results show that spatial heterogeneity in the impacts of bleaching are driven by a mix of environmental variation, habitat complexity, and differences in assemblage composition

Deletion of the thrombin cleavage domain of osteopontin mediates breast cancer cell adhesion, proteolytic activity, tumorgenicity, and metastasis

<p>Abstract</p> <p>Background</p> <p>Osteopontin (OPN) is a secreted phosphoprotein often overexpressed at high levels in the blood and primary tumors of breast cancer patients. OPN contains two integrin-binding sites and a thrombin cleavage domain located in close proximity to each other.</p> <p>Methods</p> <p>To study the role of the thrombin cleavage site of OPN, MDA-MB-468 human breast cancer cells were stably transfected with either wildtype OPN (468-OPN), mutant OPN lacking the thrombin cleavage domain (468-ΔTC) or an empty vector (468-CON) and assessed for <it>in vitro </it>and <it>in vivo </it>functional differences in malignant/metastatic behavior.</p> <p>Results</p> <p>All three cell lines were found to equivalently express thrombin, tissue factor, CD44, αvβ5 integrin and β1 integrin. Relative to 468-OPN and 468-CON cells, 468-ΔTC cells expressing OPN with a deleted thrombin cleavage domain demonstrated decreased cell adhesion (p < 0.001), decreased mRNA expression of MCAM, maspin and TRAIL (p < 0.01), and increased uPA expression and activity (p < 0.01) <it>in vitro</it>. Furthermore, injection of 468-ΔTC cells into the mammary fat pad of nude mice resulted in decreased primary tumor latency time (p < 0.01) and increased primary tumor growth and lymph node metastatic burden (p < 0.001) compared to 468-OPN and 468-CON cells.</p> <p>Conclusions</p> <p>The results presented here suggest that expression of thrombin-uncleavable OPN imparts an early tumor formation advantage as well as a metastatic advantage for breast cancer cells, possibly due to increased proteolytic activity and decreased adhesion and apoptosis. Clarification of the mechanisms responsible for these observations and the translation of this knowledge into the clinic could ultimately provide new therapeutic opportunities for combating breast cancer.</p

The accessible chromatin landscape of the human genome

DNaseI hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers, and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ~2.9 million DHSs that encompass virtually all known experimentally-validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation, and regulatory factor occupancy patterns. We connect ~580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is choreographed with dozens to hundreds of co-activated elements, and the trans-cellular DNaseI sensitivity pattern at a given region can predict cell type-specific functional behaviors. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation

Beringian Standstill and Spread of Native American Founders

Native Americans derive from a small number of Asian founders who likely arrived to the Americas via Beringia. However, additional details about the intial colonization of the Americas remain unclear. To investigate the pioneering phase in the Americas we analyzed a total of 623 complete mtDNAs from the Americas and Asia, including 20 new complete mtDNAs from the Americas and seven from Asia. This sequence data was used to direct high-resolution genotyping from 20 American and 26 Asian populations. Here we describe more genetic diversity within the founder population than was previously reported. The newly resolved phylogenetic structure suggests that ancestors of Native Americans paused when they reached Beringia, during which time New World founder lineages differentiated from their Asian sister-clades. This pause in movement was followed by a swift migration southward that distributed the founder types all the way to South America. The data also suggest more recent bi-directional gene flow between Siberia and the North American Arctic

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe