876 research outputs found

    Distinguishing environmental effects on binary black hole gravitational waveforms

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    Future gravitational wave interferometers such as the Laser Interferometer Space Antenna, Taiji, DECi-hertz Interferometer Gravitational wave Observatory and TianQin will enable precision studies of the environment surrounding black holes. These detectors will probe the millihertz frequency range, as yet unexplored by current gravitational wave detectors. Furthermore, sources will remain in band for durations of up to years, meaning that the inspiral phase of the gravitational wave signal, which can be affected by the environment, will be observable. In this paper, we study intermediate and extreme mass ratio binary black hole inspirals, and consider three possible environments surrounding the primary black hole: accretion disks, dark matter spikes and clouds of ultra-light scalar fields, also known as gravitational atoms. We present a Bayesian analysis of the detectability and measurability of these three environments. Focusing for concreteness on the case of a detection with LISA, we show that the characteristic imprint they leave on the gravitational waveform would allow us to identify the environment that generated the signal and to accurately reconstruct its model parameters.</p

    Accurate Profiling of Microbial Communities from Massively Parallel Sequencing using Convex Optimization

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    We describe the Microbial Community Reconstruction ({\bf MCR}) Problem, which is fundamental for microbiome analysis. In this problem, the goal is to reconstruct the identity and frequency of species comprising a microbial community, using short sequence reads from Massively Parallel Sequencing (MPS) data obtained for specified genomic regions. We formulate the problem mathematically as a convex optimization problem and provide sufficient conditions for identifiability, namely the ability to reconstruct species identity and frequency correctly when the data size (number of reads) grows to infinity. We discuss different metrics for assessing the quality of the reconstructed solution, including a novel phylogenetically-aware metric based on the Mahalanobis distance, and give upper-bounds on the reconstruction error for a finite number of reads under different metrics. We propose a scalable divide-and-conquer algorithm for the problem using convex optimization, which enables us to handle large problems (with ∌106\sim10^6 species). We show using numerical simulations that for realistic scenarios, where the microbial communities are sparse, our algorithm gives solutions with high accuracy, both in terms of obtaining accurate frequency, and in terms of species phylogenetic resolution.Comment: To appear in SPIRE 1

    Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens.

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    Human CD8+ cytotoxic T lymphocytes (CTLs) are known to play an important role in tumor control. In order to carry out this function, the cell surface-expressed T-cell receptor (TCR) must functionally recognize human leukocyte antigen (HLA)-restricted tumor-derived peptides (pHLA). However, we and others have shown that most TCRs bind sub-optimally to tumor antigens. Uncovering the molecular mechanisms that define this poor recognition could aid in the development of new targeted therapies that circumnavigate these shortcomings. Indeed, present therapies that lack this molecular understanding have not been universally effective. Here, we describe methods that we commonly employ in the laboratory to determine how the nature of the interaction between TCRs and pHLA governs T-cell functionality. These methods include the generation of soluble TCRs and pHLA and the use of these reagents for X-ray crystallography, biophysical analysis, and antigen-specific T-cell staining with pHLA multimers. Using these approaches and guided by structural analysis, it is possible to modify the interaction between TCRs and pHLA and to then test how these modifications impact T-cell antigen recognition. These findings have already helped to clarify the mechanism of T-cell recognition of a number of cancer antigens and could direct the development of altered peptides and modified TCRs for new cancer therapies

    A Deterministic Metaheuristic Approach using "Logistic Ants" for Combinatorial Optimization.

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    International audienceAnt algorithms are usually derived from a stochastic modeling based on some specific probability laws. We consider in this paper a full deterministic model of “logistic ants” which uses chaotic maps to govern the behavior of the artificial ants. We illustrate and test this approach on a TSP instance, and compare the results with the original Ant System algorithm. This change of paradigm —deterministic versus stochastic— implies a novel view of the internal mechanisms involved during the searching and optimizing process of ants

    Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children

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    Vitamin D is well known for its role in promoting skeletal health. Vitamin D status is determined conventionally by circulating 25-dihydroxyvitamin D (25OHD) concentration. There is evidence indicating that circulating 25OHD concentration is affected by variation in Gc, the gene encoding the vitamin D binding protein (DBP). The composite genotype of two single nucleotide polymorphisms (rs7041 and rs4588) results in different DBP isotypes (Gc1f, Gc1s and Gc2). The protein configurational differences among DBP isotypes affect DBP substrate binding affinity. The aims of this study were to determine 1) Gc variant frequencies in a population from an isolated rural region of The Gambia, West Africa (n=3129) with year-round opportunity for cutaneous vitamin D synthesis and 2) the effects of Gc variants on 25OHD concentration (n=237) in a genetically representative sub-group of children (mean (SD) age: 11.9 (4.8) years). The distribution of Gc variants was Gc1f: 0.86, Gc1s: 0.11 and Gc2: 0.03. The mean (SD) concentration of 25OHD was 59.6 (12.9) nmol/L and was significantly higher in those homozygous for Gc1f compared to other Gc variants (60.7 (13.1) vs. 56.6 (12.1) nmol/L, P=0.03). Plasma 25OHD and 1,25(OH)2D concentration was significantly associated with parathyroid hormone in Gc1f-1f but not in the other Gc variants combined. This study demonstrates that different Gc variants are associated with different 25OHD concentrations in a rural Gambian population. Gc1f-1f, thought to have the highest affinity for 25OHD, had the highest 25OHD concentration compared with lower affinity Gc variants. The considerable difference in Gc1f frequency observed in Gambians compared with other non-West African populations and associated differences in plasma 25OHD concentration, may have implications for the way in which vitamin D status should be interpreted across different ancestral groups

    A Full PFPF Shell Model Study of a~=~48 Nuclei

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    Exact diagonalizations with a minimally modified realistic force lead to detailed agreement with measured level schemes and electromagnetic transitions in 48^{48}Ca, 48^{48}Sc, 48^{48}Ti, 48^{48}V, 48^{48}Cr and 48^{48}Mn. Gamow-Teller strength functions are systematically calculated and reproduce the data to within the standard quenching factor. Their fine structure indicates that fragmentation makes much strength unobservable. As a by-product, the calculations suggest a microscopic description of the onset of rotational motion. The spectroscopic quality of the results provides strong arguments in favour of the general validity of monopole corrected realistic forces, which is discussed.Comment: 30 pages, LaTeX with epsf.sty, 14 Postscript figures included and compressed using uufiles. Completely new version of previous preprint nucl-th/9307001. FTUAM-93/01, CRN/PT 93-3

    Toward an internally consistent astronomical distance scale

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    Accurate astronomical distance determination is crucial for all fields in astrophysics, from Galactic to cosmological scales. Despite, or perhaps because of, significant efforts to determine accurate distances, using a wide range of methods, tracers, and techniques, an internally consistent astronomical distance framework has not yet been established. We review current efforts to homogenize the Local Group's distance framework, with particular emphasis on the potential of RR Lyrae stars as distance indicators, and attempt to extend this in an internally consistent manner to cosmological distances. Calibration based on Type Ia supernovae and distance determinations based on gravitational lensing represent particularly promising approaches. We provide a positive outlook to improvements to the status quo expected from future surveys, missions, and facilities. Astronomical distance determination has clearly reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press (chapter 8 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

    A single-cell Arabidopsis root atlas reveals developmental trajectories in wild-type and cell identity mutants

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    In all multicellular organisms, transcriptional networks orchestrate organ development. The Arabidopsis root, with its simple structure and indeterminate growth, is an ideal model for investigating the spatiotemporal transcriptional signatures underlying developmental trajectories. To map gene expression dynamics across root cell types and developmental time, we built a comprehensive, organ-scale atlas at single-cell resolution. In addition to estimating developmental progressions in pseudotime, we employed the mathematical concept of optimal transport to infer developmental trajectories and identify their underlying regulators. To demonstrate the utility of the atlas to interpret new datasets, we profiled mutants for two key transcriptional regulators at single-cell resolution, shortroot and scarecrow. We report transcriptomic and in vivo evidence for tissue trans-differentiation underlying a mixed cell identity phenotype in scarecrow. Our results support the atlas as a rich community resource for unraveling the transcriptional programs that specify and maintain cell identity to regulate spatiotemporal organ development

    Predictors of Virologic Failure in HIV/AIDS Patients Treated with Highly Active Antiretroviral Therapy in Brasília, Brazil During 2002–2008

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    Little data exists concerning the efficacy of the antiretroviral therapy in the Federal District in Brazil, therefore in order to improve HIV/AIDS patients’ therapy and to pinpoint hot spots in the treatment, this research work was conducted. Of 139 HIV/AIDS patients submitted to the highly active antiretroviral therapy, 12.2% failed virologically. The significant associated factors related to unresponsiveness to the lentiviral treatment were: patients’ place of origin (OR = 3.28; IC95% = 1.0–9.73; P = 0.032) and Mycobacterium tuberculosis infection (RR = 2.90; IC95% = 1.19–7.02; P = 0.019). In the logistic regression analysis, the remaining variables in the model were: patients’ birthplace (OR = 3.28; IC95% = 1.10–9.73; P = 0.032) and tuberculosis comorbidity (OR = 3.82; IC95% = 1.19–12.22; P = 0.024). The patients enrolled in this survey had an 88.0% therapeutic success rate for the maximum period of one year of treatment, predicting that T CD4+ low values and elevated viral loads at pretreatment should be particularly considered in tuberculosis coinfection, besides the availability of new antiretroviral drugs displaying optimal activity both in viral suppression and immunological reconstitution
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