134 research outputs found
PathCase-SB architecture and database design
<p>Abstract</p> <p>Background</p> <p>Integration of metabolic pathways resources and regulatory metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation in metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks.</p> <p>Description</p> <p>PathCase Systems Biology (PathCase-SB) is built and released. The PathCase-SB database provides data and API for multiple user interfaces and software tools. The current PathCase-SB system provides a database-enabled framework and web-based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate data of selected biological data sources on the web (currently, BioModels database and KEGG), and to provide more powerful and/or new capabilities via the new web-based integrative framework. This paper describes architecture and database design issues encountered in PathCase-SB's design and implementation, and presents the current design of PathCase-SB's architecture and database.</p> <p>Conclusions</p> <p>PathCase-SB architecture and database provide a highly extensible and scalable environment with easy and fast (real-time) access to the data in the database. PathCase-SB itself is already being used by researchers across the world.</p
Area Invariance of Apparent Horizons under Arbitrary Boosts
It is a well known analytic result in general relativity that the
2-dimensional area of the apparent horizon of a black hole remains invariant
regardless of the motion of the observer, and in fact is independent of the slice, which can be quite arbitrary in general relativity.
Nonetheless the explicit computation of horizon area is often substantially
more difficult in some frames (complicated by the coordinate form of the
metric), than in other frames. Here we give an explicit demonstration for very
restricted metric forms of (Schwarzschild and Kerr) vacuum black holes. In the
Kerr-Schild coordinate expression for these spacetimes they have an explicit
Lorentz-invariant form. We consider {\it boosted} versions with the black hole
moving through the coordinate system. Since these are stationary black hole
spacetimes, the apparent horizons are two dimensional cross sections of their
event horizons, so we compute the areas of apparent horizons in the boosted
space with (boosted) , and obtain the same result as in the
unboosted case. Note that while the invariance of area is generic, we deal only
with black holes in the Kerr-Schild form, and consider only one particularly
simple change of slicing which amounts to a boost. Even with these restrictions
we find that the results illuminate the physics of the horizon as a null
surface and provide a useful pedagogical tool. As far as we can determine, this
is the first explicit calculation of this type demonstrating the area
invariance of horizons. Further, these calculations are directly relevant to
transformations that arise in computational representation of moving black
holes. We present an application of this result to initial data for boosted
black holes.Comment: 19 pages, 3 figures. Added a new section and 2 plots along with a
coautho
Spin–orbit precession for eccentric black hole binaries at first order in the mass ratio
We consider spin–orbit ('geodetic') precession for a compact binary in strong-field gravity. Specifically, we compute ψ, the ratio of the accumulated spin-precession and orbital angles over one radial period, for a spinning compact body of mass m 1 and spin s 1, with , orbiting a non-rotating black hole. We show that ψ can be computed for eccentric orbits in both the gravitational self-force and post-Newtonian frameworks, and that the results appear to be consistent. We present a post-Newtonian expansion for ψ at next-to-next-to-leading order, and a Lorenz-gauge gravitational self-force calculation for ψ at first order in the mass ratio. The latter provides new numerical data in the strong-field regime to inform the effective one-body model of the gravitational two-body problem. We conclude that ψ complements the Detweiler redshift z as a key invariant quantity characterizing eccentric orbits in the gravitational two-body problem
Lot quality survey: an appealing method for rapid evaluation of vaccine coverage in developing countries – experience in Turkey
<p>Abstract</p> <p>Background</p> <p>Vaccine-preventable diseases cause significant morbidity and mortality worldwide and in developing countries in particular. Information on coverage and reasons for non-vaccination is vital to enhance overall vaccination activities. Of the several survey techniques available for investigating vaccination coverage in a given setting, the Lot Quality Technique (LQT) remains appealing and could be used in developing countries by local health personnel of district or rural health authorities to evaluate their performance in vaccination and many other health-related programs. This study aimed to evaluate vaccination coverage using LQT in a selected semi-urban setting in Turkey.</p> <p>Methods</p> <p>A LQT-based cross-sectional study was conducted in Kecioren District on a representative sample of residents aged 12–23 months in order to evaluate coverage for routine childhood vaccines, to identify health units with coverage below 75%, and to investigate reasons for non-vaccination.</p> <p>Results</p> <p>Based on self-reports, coverage for BCG, diphtheria-pertussis-tetanus (DPT-3), oral polio-3, hepatitis-3, and measles vaccines ranged between 94–99%. Coverage for measles was below 75% in five lots. The relatively high educational and socioeconomic status of parents in the study group alone could not minimize the "considerable" risk of vaccine-preventable diseases in the District and dictates a continuity of efforts for improving vaccination rates, with special emphasis on measles. We believe that administrative methods should be backed up by household surveys to strengthen vaccination monitoring and that families should be trained and motivated to have their children fully vaccinated according to the recommended schedule and in a timely manner.</p> <p>Conclusion</p> <p>This study identified vaccine coverage for seven routine vaccines completed before the age of 24 months as well as the areas requiring special attention in vaccination services. The LQT, years after its introduction to health-related research, remains an appealing technique for rapid evaluation of the extent of a variety of local health concerns in developing countries, in rural areas in particular, and is very efficient in determining performance of individual subunits in a given service area. Training of local health personnel on use of the LQT could expedite response to local health problems and could even motivate them in conducting their own surveys tailored to their professional interests.</p
Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study
Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection
Analysis of in vitro bioactivity data extracted from drug discovery literature and patents: Ranking 1654 human protein targets by assayed compounds and molecular scaffolds
<p>Abstract</p> <p>Background</p> <p>Since the classic Hopkins and Groom druggable genome review in 2002, there have been a number of publications updating both the hypothetical and successful human drug target statistics. However, listings of research targets that define the area between these two extremes are sparse because of the challenges of collating published information at the necessary scale. We have addressed this by interrogating databases, populated by expert curation, of bioactivity data extracted from patents and journal papers over the last 30 years.</p> <p>Results</p> <p>From a subset of just over 27,000 documents we have extracted a set of compound-to-target relationships for biochemical <it>in vitro </it>binding-type assay data for 1,736 human proteins and 1,654 gene identifiers. These are linked to 1,671,951 compound records derived from 823,179 unique chemical structures. The distribution showed a compounds-per-target average of 964 with a maximum of 42,869 (Factor Xa). The list includes non-targets, failed targets and cross-screening targets. The top-278 most actively pursued targets cover 90% of the compounds. We further investigated target ranking by determining the number of molecular frameworks and scaffolds. These were compared to the compound counts as alternative measures of chemical diversity on a per-target basis.</p> <p>Conclusions</p> <p>The compounds-per-protein listing generated in this work (provided as a supplementary file) represents the major proportion of the human drug target landscape defined by published data. We supplemented the simple ranking by the number of compounds assayed with additional rankings by molecular topology. These showed significant differences and provide complementary assessments of chemical tractability.</p
Pain, depression and sleep disorders in patients with diabetic and nondiabetic carpal tunnel syndrome: a vicious cycle
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