1,255 research outputs found

    Entanglement and Timing-Based Mechanisms in the Coherent Control of Scattering Processes

    Full text link
    The coherent control of scattering processes is considered, with electron impact dissociation of H2+_2^+ used as an example. The physical mechanism underlying coherently controlled stationary state scattering is exposed by analyzing a control scenario that relies on previously established entanglement requirements between the scattering partners. Specifically, initial state entanglement assures that all collisions in the scattering volume yield the desirable scattering configuration. Scattering is controlled by preparing the particular internal state wave function that leads to the favored collisional configuration in the collision volume. This insight allows coherent control to be extended to the case of time-dependent scattering. Specifically, we identify reactive scattering scenarios using incident wave packets of translational motion where coherent control is operational and initial state entanglement is unnecessary. Both the stationary and time-dependent scenarios incorporate extended coherence features, making them physically distinct. From a theoretical point of view, this work represents a large step forward in the qualitative understanding of coherently controlled reactive scattering. From an experimental viewpoint, it offers an alternative to entanglement-based control schemes. However, both methods present significant challenges to existing experimental technologies

    DNA methylation and differential gene regulation in photoreceptor cell death

    Get PDF
    Retinitis pigmentosa (RP) defines a group of inherited degenerative retinal diseases causing progressive loss of photoreceptors. To this day, RP is still untreatable and rational treatment development will require a thorough understanding of the underlying cell death mechanisms. Methylation of the DNA base cytosine by DNA methyltransferases (DNMTs) is an important epigenetic factor regulating gene expression, cell differentiation, cell death, and survival. Previous studies suggested an involvement of epigenetic mechanisms in RP, and in this study, increased cytosine methylation was detected in dying photoreceptors in the rd1, rd2, P23H, and S334ter rodent models for RP. Ultrastructural analysis of photoreceptor nuclear morphology in the rd1 mouse model for RP revealed a severely altered chromatin structure during retinal degeneration that coincided with an increased expression of the DNMT isozyme DNMT3a. To identify disease-specific differentially methylated DNA regions (DMRs) on a genomic level, we immunoprecipitated methylated DNA fragments and subsequently analyzed them with a targeted microarray. Genome-wide comparison of DMRs between rd1 and wild-type retina revealed hypermethylation of genes involved in cell death and survival as well as cell morphology and nervous system development. When correlating DMRs with gene expression data, we found that hypermethylation occurred alongside transcriptional repression. Consistently, motif analysis showed that binding sites of several important transcription factors for retinal physiology were hypermethylated in the mutant model, which also correlated with transcriptional silencing of their respective target genes. Finally, inhibition of DNMTs in rd1 organotypic retinal explants using decitabine resulted in a substantial reduction of photoreceptor cell death, suggesting inhibition of DNA methylation as a potential novel treatment in RP

    Climate variability and human impact in South America during the last 2000 years: synthesis and perspectives from pollen records

    Get PDF
    An improved understanding of present-day climate variability and change relies on high-quality data sets from the past 2 millennia. Global efforts to model regional climate modes are in the process of being validated against, and integrated with, records of past vegetation change. For South America, however, the full potential of vegetation records for evaluating and improving climate models has hitherto not been sufficiently acknowledged due to an absence of information on the spatial and temporal coverage of study sites. This paper therefore serves as a guide to high-quality pollen records that capture environmental variability during the last 2 millennia. We identify 60 vegetation (pollen) records from across South America which satisfy geochronological requirements set out for climate modelling, and we discuss their sensitivity to the spatial signature of climate modes throughout the continent. Diverse patterns of vegetation response to climate change are observed, with more similar patterns of change in the lowlands and varying intensity and direction of responses in the highlands. Pollen records display local-scale responses to climate modes; thus, it is necessary to understand how vegetation–climate interactions might diverge under variable settings. We provide a qualitative translation from pollen metrics to climate variables. Additionally, pollen is an excellent indicator of human impact through time. We discuss evidence for human land use in pollen records and provide an overview considered useful for archaeological hypothesis testing and important in distinguishing natural from anthropogenically driven vegetation change. We stress the need for the palynological community to be more familiar with climate variability patterns to correctly attribute the potential causes of observed vegetation dynamics. This manuscript forms part of the wider LOng-Term multi-proxy climate REconstructions and Dynamics in South America – 2k initiative that provides the ideal framework for the integration of the various palaeoclimatic subdisciplines and palaeo-science, thereby jump-starting and fostering multidisciplinary research into environmental change on centennial and millennial timescales

    Bayesian hierarchical clustering for studying cancer gene expression data with unknown statistics

    Get PDF
    Clustering analysis is an important tool in studying gene expression data. The Bayesian hierarchical clustering (BHC) algorithm can automatically infer the number of clusters and uses Bayesian model selection to improve clustering quality. In this paper, we present an extension of the BHC algorithm. Our Gaussian BHC (GBHC) algorithm represents data as a mixture of Gaussian distributions. It uses normal-gamma distribution as a conjugate prior on the mean and precision of each of the Gaussian components. We tested GBHC over 11 cancer and 3 synthetic datasets. The results on cancer datasets show that in sample clustering, GBHC on average produces a clustering partition that is more concordant with the ground truth than those obtained from other commonly used algorithms. Furthermore, GBHC frequently infers the number of clusters that is often close to the ground truth. In gene clustering, GBHC also produces a clustering partition that is more biologically plausible than several other state-of-the-art methods. This suggests GBHC as an alternative tool for studying gene expression data. The implementation of GBHC is available at https://sites. google.com/site/gaussianbhc

    Impact of coronavirus syndromes on physical and mental health of health care workers: Systematic review and meta-analysis

    Get PDF
    Background: Health care workers (HCW) are at high risk of developing physical/mental health outcomes related to coronavirus syndromes. Nature and frequency of these outcomes are undetermined. Methods: PRISMA/MOOSE-compliant (PROSPERO-CRD42020180205) systematic review of Web of Science/grey literature until 15th April 2020, to identify studies reporting physical/mental health outcomes in HCW infected/exposed to Severe Acute Respiratory Syndrome -SARS-, Middle East Respiratory Syndrome -MERS-, Novel coronavirus -COVID-19-. Proportion random effect meta-analyses, I2 statistic, quality assessment and sensitivity analysis. Results: 115 articles were included (n=60,458 HCW, age 36.1Β±7.1, 77.1% female). Physical health outcomes: 75.9% HCW infected by SARS/MERS/COVID-19 reported fever (95%CI=65.9–83.7%, k=12, n=949), 47.9% cough (95%CI=39.2–56.8%, k=14, n=970), 43.6% myalgias (95%CI=31.9–56.0%, k=13, n=898), 42.3% chills (95%CI=20.2–67.9%, k=7, n=716), 41.2% fatigue (95%CI=18.2–68.8%, k=6, n=386), 34.6% headaches (95%CI=23.1–48.2%, k=11, n=893), 31.2% dyspnoea (95%CI=23.2–40.5%, k=12, n=1003), 25.3% sore throat (95%CI=18.8–33.2%, k=8, n=747), 22.2% nausea/vomiting (95%CI=14.9–31.8%, k=6, n=662), 18.8% diarrhoea (95%CI=11.9–28.4%, k=9, n=824). Mental health outcomes: 62.5% HCW exposed to SARS/MERS/COVID-19 reported general health concerns (95%CI=57.0–67,8%, k=2, n=2254), 43.7% fear (95%CI=33.9–54.0%, k=4, n=584), 37.9% insomnia (95%CI=30.9–45.5%, k=6, n=5067), 37.8% psychological distress (95%CI=28.4–48.2%, k=15, n=24,346), 34.4% burnout (95%CI=19.3–53.5%, k=3, n=1337), 29.0% anxiety features (95%CI=14.2–50.3%, k=6, n=9191), 26.3% depressive symptoms (95%CI=12.5–47.1%, k=8, n=9893), 20.7% post-traumatic stress disorder features (95%CI=13.2–31%, k=11, n=3826), 16.1% somatisation (95%CI=0.2–96.0%, k=2, n=2184), 14.0% stigmatisation feelings (95%CI=6.4–28.1%, k=2, n=411). Limitations: Limited amount of evidence for some outcomes and suboptimal design in several studies included. Conclusions: SARS/MERS/COVID-19 have a substantial impact on the physical and mental health of HCW, which should become a priority for public health strategies

    Using Genetic Diversity in Deep Root Systems of Perennial Forage Grasses and Rice to Capture Carbon in Tropical Soils

    Get PDF
    Agricultural soils have the potential not only to be sinks of carbon dioxide (CO2) but also to mitigate the emissions of this gas to the atmosphere, thus, alleviating global warming. Perennial tropical grasses and rice upland and lowland varieties exhibit a large untapped genetic diversity in their root systems (e.g., deep rooting ability, exudation rates and chemical composition) that, if unlocked, could contribute to increased food production in crop-livestock systems while enhancing soil organic carbon (SOC) in tropical regions. Naturebased solutions that improve crop adaptation and SOC storage in tropical soils could help to remove CO2 from the atmosphere and thereby benefit the global climate system. With the launch of Future Seeds, one of the world’s largest repositories of tropical crop varieties, the Bezos Earth Fund (BEF) granted a major project within the Program of Future of Food. The focus of this BEF funded project is to: (i) develop novel high-throughput phenotyping methods to evaluate genetic diversity of root systems of tropical grasses and rice; (ii) unravel the potential of root systems in crop-livestock systems to replenish soil organic carbon (SOC) in human-intervened areas in tropical soils; (iii) identify and target hotspots/agroecological niches for SOC storage in tropical soils; and (iv) build capacity in conducting research on root systems and SOC storage towards carbon farming in tropical regions. Implementation of land-based SOC storage practices/projects (through carbon markets) based on deep rooting ability of perennial tropical forage grasses and rice cultivars in crop-pasture rotational systems could significantly reduce net emissions from tropical soils

    Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells

    Get PDF
    The platinum compound oxaliplatin has been shown to be an effective chemotherapeutic agent for the treatment of colorectal cancer. In this study, we investigate the molecular mechanisms of action of oxaliplatin to identify means of predicting response to this agent. Exposure of colon cancer cells to oxaliplatin resulted in G2/M arrest and apoptosis. Immunofluorescent staining demonstrated that the apoptotic cascade initiated by oxaliplatin is characterised by translocation of Bax to the mitochondria and cytochrome c release into the cytosol. Oxaliplatin treatment resulted in caspase 3 activation and oxaliplatin-induced apoptosis was abrogated by inhibition of caspase activity with z-VAD-fmk, but was independent of Fas/FasL association. Targeted inactivation of Bax or p53 in HCT116 cells resulted in significantly increased resistance to oxaliplatin. However, the mutational status of p53 was unable to predict response to oxaliplatin in a panel of 30 different colorectal cancer cell lines. In contrast, the expression profile of these 30 cell lines, assessed using a 9216-sequence cDNA microarray, successfully predicted the apoptotic response to oxaliplatin. A leave-one-out cross-validation approach was used to demonstrate a significant correlation between experimentally observed and expression profile predicted apoptosis in response to clinically achievable doses of oxaliplatin (R=0.53; P=0.002). In addition, these microarray experiments identified several genes involved in control of apoptosis and DNA damage repair that were significantly correlated with response to oxaliplatin

    Strategic Transformations in the Media

    Get PDF
    Digital technologies have transformed the way many media organisations have conducted their business over the past two decades. This transformational context raises a number of important questions for media management researchers. Firstly, how have media firms adapted their strategies, resources and capabilities in response to the challenges presented by an increasingly digital environment? Secondly, how have these adaptive practices affected their corporate financial performance? This paper advances our theoretical understanding of media firm transformation by using a multi-disciplinary approach that draws on knowledge from corporate strategy, dynamic capabilities and firm performance. This integrated approach provides a more holistic view of strategic business transformation by understanding the strategic arguments that compel firm’s to reconfigure their resources and capabilities in a dynamic business environment

    c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis

    Get PDF
    The proto-oncogene c-Myc is overexpressed in 70% of colorectal tumours and can modulate proliferation and apoptosis after cytotoxic insult. Using an isogenic cell system, we demonstrate that c-Myc overexpression in colon carcinoma LoVo cells resulted in sensitisation to camptothecin-induced apoptosis, thus identifying c-Myc as a potential marker predicting response of colorectal tumour cells to camptothecin. Both camptothecin exposure and c-Myc overexpression in LoVo cells resulted in elevation of p53 protein levels, suggesting a role of p53 in the c-Myc-imposed sensitisation to the apoptotic effects of camptothecin. This was confirmed by the ability of PFT-alpha, a specific inhibitor of p53, to attenuate camptothecin-induced apoptosis. p53 can induce the expression of p21(Waf1/Cip1), an antiproliferative protein that can facilitate DNA repair and drug resistance. Importantly, although camptothecin treatment markedly increased p21(Waf1/Cip1) levels in parental LoVo cells, this effect was abrogated in c-Myc-overexpressing derivatives. Targeted inactivation of p21(Waf1/Cip1) in HCT116 colon cancer cells resulted in significantly increased levels of apoptosis following treatment with camptothecin, demonstrating the importance of p21(Waf1/Cip1) in the response to this agent. Finally, cDNA microarray analysis was used to identify genes that are modulated in expression by c-Myc upregulation that could serve as additional markers predicting response to camptothecin. Thirty-four sequences were altered in expression over four-fold in two isogenic c-Myc-overexpressing clones compared to parental LoVo cells. Moreover, the expression of 10 of these genes was confirmed to be significantly correlated with response to camptothecin in a panel of 30 colorectal cancer cell lines
    • …
    corecore