922 research outputs found

    Quenched QCD at finite density

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    Simulations of quenched QCDQCD at relatively small but {\it nonzero} chemical potential μ\mu on 32×16332 \times 16^3 lattices indicate that the nucleon screening mass decreases linearly as μ\mu increases predicting a critical chemical potential of one third the nucleon mass, mN/3m_N/3, by extrapolation. The meson spectrum does not change as μ\mu increases over the same range, from zero to mπ/2m_\pi/2. Past studies of quenched lattice QCD have suggested that there is phase transition at μ=mπ/2\mu = m_\pi/2. We provide alternative explanations for these results, and find a number of technical reasons why standard lattice simulation techniques suffer from greatly enhanced fluctuations and finite size effects for μ\mu ranging from mπ/2m_\pi/2 to mN/3m_N/3. We find evidence for such problems in our simulations, and suggest that they can be surmounted by improved measurement techniques.Comment: 23 pages, Revte

    Adaptive mesh refinement approach to construction of initial data for black hole collisions

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    The initial data for black hole collisions is constructed using a conformal-imaging approach and a new adaptive mesh refinement technique, a fully threaded tree (FTT). We developed a second-order accurate approach to the solution of the constraint equations on a non-uniformly refined high resolution Cartesian mesh including second-order accurate treatment of boundary conditions at the black hole throats. Results of test computations show convergence of the solution as the numerical resolution is increased. FTT-based mesh refinement reduces the required memory and computer time by several orders of magnitude compared to a uniform grid. This opens up the possibility of using Cartesian meshes for very high resolution simulations of black hole collisions.Comment: 13 pages, 11 figure

    Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

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    Abstract Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be involved in AMD pathogenesis. Conclusions We discovered new global biomarkers and gene expression signatures of AMD. These results are consistent with a model whereby cell-based inflammatory responses represent a central feature of AMD etiology, and depending on genetics, environment, or stochastic factors, may give rise to the advanced AMD phenotypes characterized by angiogenesis and/or cell death. Genes regulating these immunological activities, along with numerous other genes identified here, represent promising new targets for AMD-directed therapeutics and diagnostics. Please see related commentary: http://www.biomedcentral.com/1741-7015/10/21/abstrac

    Beyond freeze-drying of biologics: vacuum-foam drying and spray freeze-drying

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    [EN] The complexity of biotherapeutics in development continues to increase as our capability in discovery and recombinant technology improves. While safety and efficacy remain the two critical aspects of all therapeutics, ensuring adequate stability is a challenge. Freeze-drying is a commonly-used processing technique to enhance the stability of biotherapeutic products, although the lengthy process time and low energy efficiency have led to the search for, and evaluation of, next-generation drying technologies, including spray freeze-drying and vaccum-foam drying. Both processes result in dosage forms that vary considerably from those produced by lyophilization and possess physical properties that may be deemed superior for their intended applications.Langford, A.; Balthazor, B.; Bhatnagar, B.; Tchessalov, S.; Hageman, M.; Lukas, A.; Plitzko, M.... (2018). Beyond freeze-drying of biologics: vacuum-foam drying and spray freeze-drying. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 41-48. https://doi.org/10.4995/IDS2018.2018.7855OCS414

    'Once there is life, there is hope' Ebola survivors' experiences, behaviours and attitudes in Sierra Leone, 2015.

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    BACKGROUND: In Sierra Leone, over 4000 individuals survived Ebola since the outbreak began in 2014. Because Ebola survivorship was largely unprecedented prior to this outbreak, little is known about survivor experiences during and post illness. METHODS: To assess survivors' experiences and attitudes related to Ebola, 28 in-depth interviews and short quantitative surveys with survivors from all four geographic regions of Sierra Leone were conducted in May 2015. RESULTS: Survivor experiences, emotions and attitudes changed over time as they moved from disease onset to treatment, discharge and life post-discharge. Survivors mentioned experiencing acute fear and depression when they fell ill. Only half reported positive experiences in holding centres but nearly all were positive about their treatment centre experiences. Survivor euphoria on discharge was followed by concerns about their financial situation and future. While all reported supportive attitudes from family members, about a third described discrimination and stigma from their communities. Over a third became unemployed, especially those previously engaged in petty trade. Survivor knowledge about sexual transmission risk reflected counselling messages. Many expressed altruistic motivations for abstinence or condom use. In addition, survivors were strongly motivated to help end Ebola and to improve the healthcare system. Key recommendations from survivors included improved counselling in holding centres and long-term government support for survivors, including opportunities for participation in Ebola response efforts. CONCLUSIONS: Survivors face myriad economic, social and health challenges. Addressing survivor concerns, including the discrimination they face, could facilitate their reintegration into communities and their contributions to future Ebola responses

    Simplivariate Models: Ideas and First Examples

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    One of the new expanding areas in functional genomics is metabolomics: measuring the metabolome of an organism. Data being generated in metabolomics studies are very diverse in nature depending on the design underlying the experiment. Traditionally, variation in measurements is conceptually broken down in systematic variation and noise where the latter contains, e.g. technical variation. There is increasing evidence that this distinction does not hold (or is too simple) for metabolomics data. A more useful distinction is in terms of informative and non-informative variation where informative relates to the problem being studied. In most common methods for analyzing metabolomics (or any other high-dimensional x-omics) data this distinction is ignored thereby severely hampering the results of the analysis. This leads to poorly interpretable models and may even obscure the relevant biological information. We developed a framework from first data analysis principles by explicitly formulating the problem of analyzing metabolomics data in terms of informative and non-informative parts. This framework allows for flexible interactions with the biologists involved in formulating prior knowledge of underlying structures. The basic idea is that the informative parts of the complex metabolomics data are approximated by simple components with a biological meaning, e.g. in terms of metabolic pathways or their regulation. Hence, we termed the framework ‘simplivariate models’ which constitutes a new way of looking at metabolomics data. The framework is given in its full generality and exemplified with two methods, IDR analysis and plaid modeling, that fit into the framework. Using this strategy of ‘divide and conquer’, we show that meaningful simplivariate models can be obtained using a real-life microbial metabolomics data set. For instance, one of the simple components contained all the measured intermediates of the Krebs cycle of E. coli. Moreover, these simplivariate models were able to uncover regulatory mechanisms present in the phenylalanine biosynthesis route of E. coli

    Visualizing the Anthropocene dialectically: Jessica Woodworth and Peter Brosens’ eco-crisis trilogy

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    The ambition of this article is to propose a way of visualizing the Anthropocene dialectically. As suggested by the Dutch atmospheric chemist Paul Crutzen and the professor of biology Eugene F. Stoermer, the term Anthropocene refers to a historical period in which humankind has turned into a geological force that transforms the natural environment in such a way that it is hard to distinguish between the human and the natural world. Crutzen and Stoermer explain that the Anthropocene has begun after the Holocene, the geological epoch that followed the last ice age and lasted until the industrial revolution. Drawing on a number of figures such as the “tenfold” increase in urbanisation, the extreme transformation of land surface by human action, the use of more than 50% of all accessible fresh water by humans, and the massive increase in greenhouse emissions, Crutzen and Stoermer conclude that the term Anthropocene describes aptly mankind's influence on ecological and geological cycles (Crutzen & Stoermer, 2000, p.17). The wager of this article is that we need to identify ways to visualize the Anthropocene dialectically and I proceed to do so using as a case study Jessica Woodworth's and Peter Brosen's trilogy on the conflict between humans and nature, which consists of Khadak (2006), Altiplano (2009), and The Fifth Season (La Cinquième Saison, 2012)

    A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice

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    © 2020, The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0
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