105 research outputs found
Static charged perfect fluid spheres in general relativity
Interior perfect fluid solutions for the Reissner-Nordstrom metric are
studied on the basis of a new classification scheme. General formulas are found
in many cases. Explicit new global solutions are given as illustrations. Known
solutions are briefly reviewed.Comment: 23 pages, Revtex (galley), journal version, to appear in Phys.Rev.
Triangleland. I. Classical dynamics with exchange of relative angular momentum
In Euclidean relational particle mechanics, only relative times, relative
angles and relative separations are meaningful. Barbour--Bertotti (1982) theory
is of this form and can be viewed as a recovery of (a portion of) Newtonian
mechanics from relational premises. This is of interest in the absolute versus
relative motion debate and also shares a number of features with the
geometrodynamical formulation of general relativity, making it suitable for
some modelling of the problem of time in quantum gravity. I also study
similarity relational particle mechanics (`dynamics of pure shape'), in which
only relative times, relative angles and {\sl ratios of} relative separations
are meaningful. This I consider firstly as it is simpler, particularly in 1 and
2 d, for which the configuration space geometry turns out to be well-known,
e.g. S^2 for the `triangleland' (3-particle) case that I consider in detail.
Secondly, the similarity model occurs as a sub-model within the Euclidean
model: that admits a shape--scale split. For harmonic oscillator like
potentials, similarity triangleland model turns out to have the same
mathematics as a family of rigid rotor problems, while the Euclidean case turns
out to have parallels with the Kepler--Coulomb problem in spherical and
parabolic coordinates. Previous work on relational mechanics covered cases
where the constituent subsystems do not exchange relative angular momentum,
which is a simplifying (but in some ways undesirable) feature paralleling
centrality in ordinary mechanics. In this paper I lift this restriction. In
each case I reduce the relational problem to a standard one, thus obtain
various exact, asymptotic and numerical solutions, and then recast these into
the original mechanical variables for physical interpretation.Comment: Journal Reference added, minor updates to References and Figure
Foundations of Relational Particle Dynamics
Relational particle dynamics include the dynamics of pure shape and cases in
which absolute scale or absolute rotation are additionally meaningful. These
are interesting as regards the absolute versus relative motion debate as well
as discussion of conceptual issues connected with the problem of time in
quantum gravity. In spatial dimension 1 and 2 the relative configuration spaces
of shapes are n-spheres and complex projective spaces, from which knowledge I
construct natural mechanics on these spaces. I also show that these coincide
with Barbour's indirectly-constructed relational dynamics by performing a full
reduction on the latter. Then the identification of the configuration spaces as
n-spheres and complex projective spaces, for which spaces much mathematics is
available, significantly advances the understanding of Barbour's relational
theory in spatial dimensions 1 and 2. I also provide the parallel study of a
new theory for which positon and scale are purely relative but orientation is
absolute. The configuration space for this is an n-sphere regardless of the
spatial dimension, which renders this theory a more tractable arena for
investigation of implications of scale invariance than Barbour's theory itself.Comment: Minor typos corrected; references update
The farther, the safer: a manifesto for securely navigating synthetic species away from the old living world
Biotechnology has empirically established that it is easier to construct and evaluate variant genes and proteins than to account for the emergence and function of wild-type macromolecules. Systematizing this constructive approach, synthetic biology now promises to infer and assemble entirely novel genomes, cells and ecosystems. It is argued here that the theoretical and computational tools needed for this endeavor are missing altogether. However, such tools may not be required for diversifying organisms at the basic level of their chemical constitution by adding, substituting or removing elements and molecular components through directed evolution under selection. Most importantly, chemical diversification of life forms could be designed to block metabolic cross-feed and genetic cross-talk between synthetic and wild species and hence protect natural habitats and human health through novel types of containment
Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients
Background
Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown.
Methods
Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding.
Results
A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55).
Conclusions
Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.
Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study
Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection
Functional Characterization of FLT3 Receptor Signaling Deregulation in Acute Myeloid Leukemia by Single Cell Network Profiling (SCNP)
Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD) and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative.Using single cell network profiling (SCNP), cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb) and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT) or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L), including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling deregulation and provide additional information for disease characterization and management.These studies show the feasibility of SCNP to assess modulated intracellular signaling pathways and characterize the biology of individual AML samples in the context of genetic alterations
The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance
The James Webb Space Telescope (JWST) is a large, infrared space telescope
that has recently started its science program which will enable breakthroughs
in astrophysics and planetary science. Notably, JWST will provide the very
first observations of the earliest luminous objects in the Universe and start a
new era of exoplanet atmospheric characterization. This transformative science
is enabled by a 6.6 m telescope that is passively cooled with a 5-layer
sunshield. The primary mirror is comprised of 18 controllable, low areal
density hexagonal segments, that were aligned and phased relative to each other
in orbit using innovative image-based wavefront sensing and control algorithms.
This revolutionary telescope took more than two decades to develop with a
widely distributed team across engineering disciplines. We present an overview
of the telescope requirements, architecture, development, superb on-orbit
performance, and lessons learned. JWST successfully demonstrates a segmented
aperture space telescope and establishes a path to building even larger space
telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25
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