482 research outputs found
Variational Methods for Biomolecular Modeling
Structure, function and dynamics of many biomolecular systems can be
characterized by the energetic variational principle and the corresponding
systems of partial differential equations (PDEs). This principle allows us to
focus on the identification of essential energetic components, the optimal
parametrization of energies, and the efficient computational implementation of
energy variation or minimization. Given the fact that complex biomolecular
systems are structurally non-uniform and their interactions occur through
contact interfaces, their free energies are associated with various interfaces
as well, such as solute-solvent interface, molecular binding interface, lipid
domain interface, and membrane surfaces. This fact motivates the inclusion of
interface geometry, particular its curvatures, to the parametrization of free
energies. Applications of such interface geometry based energetic variational
principles are illustrated through three concrete topics: the multiscale
modeling of biomolecular electrostatics and solvation that includes the
curvature energy of the molecular surface, the formation of microdomains on
lipid membrane due to the geometric and molecular mechanics at the lipid
interface, and the mean curvature driven protein localization on membrane
surfaces. By further implicitly representing the interface using a phase field
function over the entire domain, one can simulate the dynamics of the interface
and the corresponding energy variation by evolving the phase field function,
achieving significant reduction of the number of degrees of freedom and
computational complexity. Strategies for improving the efficiency of
computational implementations and for extending applications to coarse-graining
or multiscale molecular simulations are outlined.Comment: 36 page
Foundations of Black Hole Accretion Disk Theory
This review covers the main aspects of black hole accretion disk theory. We
begin with the view that one of the main goals of the theory is to better
understand the nature of black holes themselves. In this light we discuss how
accretion disks might reveal some of the unique signatures of strong gravity:
the event horizon, the innermost stable circular orbit, and the ergosphere. We
then review, from a first-principles perspective, the physical processes at
play in accretion disks. This leads us to the four primary accretion disk
models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin)
disks, slim disks, and advection-dominated accretion flows (ADAFs). After
presenting the models we discuss issues of stability, oscillations, and jets.
Following our review of the analytic work, we take a parallel approach in
reviewing numerical studies of black hole accretion disks. We finish with a few
select applications that highlight particular astrophysical applications:
measurements of black hole mass and spin, black hole vs. neutron star accretion
disks, black hole accretion disk spectral states, and quasi-periodic
oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at
http://www.livingreviews.org/lrr-2013-
The Formation of the First Massive Black Holes
Supermassive black holes (SMBHs) are common in local galactic nuclei, and
SMBHs as massive as several billion solar masses already exist at redshift z=6.
These earliest SMBHs may grow by the combination of radiation-pressure-limited
accretion and mergers of stellar-mass seed BHs, left behind by the first
generation of metal-free stars, or may be formed by more rapid direct collapse
of gas in rare special environments where dense gas can accumulate without
first fragmenting into stars. This chapter offers a review of these two
competing scenarios, as well as some more exotic alternative ideas. It also
briefly discusses how the different models may be distinguished in the future
by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First
Galaxies - Theoretical Predictions and Observational Clues", Springer
Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B.
Mobasher, in pres
Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)
This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0βD*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4ββfb-1 collected at the Ξ₯(4S) resonance during 1999β2000, we have reconstructed 38 candidate signal events in the mode B0βD*+D*- with an estimated background of 6.2Β±0.5 events. From these events, we determine the branching fraction to be B(B0βD*+D*-)=[8.3Β±1.6(stat)Β±1.2(syst)]Γ10-4. The measured CP-odd fraction of the final state is 0.22Β±0.18(stat)Β±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation
Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at βs=10.6 GeV
This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qqΜ
continuum events near the Ξ₯(4S) resonance are presented. Using 20.8 fb-1 of data on the Ξ₯(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(BβDs+X)=(10.93Β±0.19Β±0.58Β±2.73)% and B(BβDs*+X)=(7.9Β±0.8Β±0.7Β±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+βΟΟ+ branching fraction uncertainty. The production cross sections Ο(e+e-βDs+X)ΓB(Ds+βΟΟ+)=7.55Β±0.20Β±0.34pb and Ο(e+e-βDs*Β±X)ΓB(Ds+βΟΟ+)=5.8Β±0.7Β±0.5pb are measured at center-of-mass energies about 40 MeV below the Ξ₯(4S) mass. The branching fractions Ξ£B(BβDs(*)+D(*))=(5.07Β±0.14Β±0.30Β±1.27)% and Ξ£B(BβDs*+D(*))=(4.1Β±0.2Β±0.4Β±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4Β±0.1Β±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation
Search for rare quark-annihilation decays, B --> Ds(*) Phi
We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context
of the Standard Model, these decays are expected to be highly suppressed since
they proceed through annihilation of the b and u-bar quarks in the B- meson.
Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected
with the BABAR detector at SLAC. We find no evidence for these decays, and we
set Bayesian 90% confidence level upper limits on the branching fractions BF(B-
--> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results
are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid
Communications
HIV-1 Tat Co-Operates with IFN-Ξ³ and TNF-Ξ± to Increase CXCL10 in Human Astrocytes
HIV-associated neurological disorders (HAND) are estimated to affect 60% of the HIV infected population. HIV-encephalitis (HIVE), the pathological correlate of the most severe form of HAND is often characterized by glial activation, cytokine/chemokine dysregulation, and neuronal damage and loss. However, the severity of HIVE correlates better with glial activation rather than viral load. One of the characteristic features of HIVE is the increased amount of the neurotoxic chemokine, CXCL10. This chemokine can be released from astroglia activated with the pro-inflammatory cytokines IFN-Ξ³ and TNF-Ξ±, in conjunction with HIV-1 Tat, all of which are elevated in HIVE. In an effort to understand the pathogenesis of HAND, this study was aimed at exploring the regulation of CXCL10 by cellular and viral factors during astrocyte activation. Specifically, the data herein demonstrate that the combined actions of HIV-1 Tat and the pro-inflammatory cytokines, IFN-Ξ³ and TNF-Ξ±, result in the induction of CXCL10 at both the RNA and protein level. Furthermore, CXCL10 induction was found to be regulated transcriptionally by the activation of the p38, Jnk, and Akt signaling pathways and their downstream transcription factors, NF-ΞΊB and STAT-1Ξ±. Since CXCL10 levels are linked to disease severity, understanding its regulation could aid in the development of therapeutic intervention strategies for HAND
Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice
Background Recent in vivo and in vitro studies in non-neuronal and neuronal tissues have shown that different pathways of macrophage activation result in cells with different properties. Interleukin (IL)-6 triggers the classically activated inflammatory macrophages (M1 phenotype), whereas the alternatively activated macrophages (M2 phenotype) are anti-inflammatory. The objective of this study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL-6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on macrophage activation and the inflammatory response in the acute phase after spinal cord injury (SCI) in mice. Methods MR16-1 antibodies versus isotype control antibodies or saline alone were administered immediately after thoracic SCI in mice. SC tissue repair was compared between the two groups by Luxol fast blue (LFB) staining for myelination and immunoreactivity for the neuronal markers growth-associated protein (GAP)-43 and neurofilament heavy 200 kDa (NF-H) and for locomotor function. The expression of T helper (Th)1 cytokines (interferon (IFN)-? and tumor necrosis factor-a) and Th2 cytokines (IL-4, IL-13) was determined by immunoblot analysis. The presence of M1 (inducible nitric oxide synthase (iNOS)-positive, CD16/32-positive) and M2 (arginase 1-positive, CD206-positive) macrophages was determined by immunohistology. Using flow cytometry, we also quantified IFN-? and IL-4 levels in neutrophils, microglia, and macrophages, and Mac-2 (macrophage antigen-2) and Mac-3 in M2 macrophages and microglia. Results LFB-positive spared myelin was increased in the MR16-1-treated group compared with the controls, and this increase correlated with enhanced positivity for GAP-43 or NF-H, and improved locomotor Basso Mouse Scale scores. Immunoblot analysis of the MR16-1-treated samples identified downregulation of Th1 and upregulation of Th2 cytokines. Whereas iNOS-positive, CD16/32-positive M1 macrophages were the predominant phenotype in the injured SC of non-treated control mice, MR16-1 treatment promoted arginase 1-positive, CD206-positive M2 macrophages, with preferential localization of these cells at the injury site. MR16-1 treatment suppressed the number of IFN-?-positive neutrophils, and increased the number of microglia present and their positivity for IL-4. Among the arginase 1-positive M2 macrophages, MR16-1 treatment increased positivity for Mac-2 and Mac-3, suggestive of increased phagocytic behavior. Conclusion The results suggest that temporal blockade of IL-6 signaling after SCI abrogates damaging inflammatory activity and promotes functional recovery by promoting the formation of alternatively activated M2 macrophages
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