1,595 research outputs found
Introductory Remarks
On April 24, 1985, the Association of the Bar of the Cirty of New York sponsored a Symposium addressing the use and impact of the amended verstion of Rule 11 of the Federal Rules of Civil Procedure. What follows is a transcript of those proceedings
Intrinsic Decoherence Dynamics in Smooth Hamiltonian Systems: Quantum-classical Correspondence
A direct classical analog of the quantum dynamics of intrinsic decoherence in
Hamiltonian systems, characterized by the time dependence of the linear entropy
of the reduced density operator, is introduced. The similarities and
differences between the classical and quantum decoherence dynamics of an
initial quantum state are exposed using both analytical and computational
results. In particular, the classicality of early-time intrinsic decoherence
dynamics is explored analytically using a second-order perturbative treatment,
and an interesting connection between decoherence rates and the stability
nature of classical trajectories is revealed in a simple approximate classical
theory of intrinsic decoherence dynamics. The results offer new insights into
decoherence, dynamics of quantum entanglement, and quantum chaos.Comment: 12 pages, 7 figures, to appear in Physical Review
Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase
Aspartate transcarbamoylase catalyzes the second step of de-novo pyrimidine biosynthesis. As malarial parasites lack pyrimidine salvage machinery and rely on de-novo production for growth and proliferation, this pathway is a target for drug discovery. Previously, an apo crystal structure of aspartate transcarbamoylase from Plasmodium falciparum (PfATC) in its T-state has been reported. Here we present crystal structures of PfATC in the liganded R-state as well as in complex with the novel inhibitor, 2,3-napthalenediol, identified by high-throughput screening. Our data shows that 2,3-napthalediol binds in close proximity to the active site, implying an allosteric mechanism of inhibition. Furthermore, we report biophysical characterization of 2,3-napthalenediol. These data provide a promising starting point for structure based drug design targeting PfATC and malarial de-novo pyrimidine biosynthesis
Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases
Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, is a mitochondrial enzyme which catalyzes the transfer of sulfur in several molecular pathways. After its initial identification as a cyanide detoxification enzyme, it was found that its functions also include sulfur metabolism, modification of iron-sulfur clusters and the reduction of antioxidants glutathione and thioredoxin. TST deficiency was shown to be strongly related to the pathophysiology of metabolic diseases including diabetes and obesity. This review summarizes research related to the enzymatic properties and functions of TST, to then explore the association between the effects of TST on mitochondria and development of diseases such as diabetes and obesity
Probing the role of the divalent metal ion in uteroferrin using metal ion replacement and a comparison to isostructural biomimetics
Purple acid phosphatases (PAPs) are a group of
heterovalent binuclear metalloenzymes that catalyze the
hydrolysis of phosphomonoesters at acidic to neutral pH.
While the metal ions are essential for catalysis, their precise
roles are not fully understood. Here, the Fe(III)Ni(II)
derivative of pig PAP (uteroferrin) was generated and its
properties were compared with those of the native
Fe(III)Fe(II) enzyme. The kcat of the Fe(III)Ni(II) derivative
(approximately 60 s–1) is approximately 20% of that of
native uteroferrin, and the Ni(II) uptake is considerably
faster than the reconstitution of full enzymatic activity,
suggesting a slow conformational change is required to
attain optimal reactivity. An analysis of the pH dependence
of the catalytic properties of Fe(III)Ni(II) uteroferrin indicates
that the l-hydroxide is the likely nucleophile. Thus,
the Ni(II) derivative employs a mechanism similar to that
proposed for the Ga(III)Zn(II) derivative of uteroferrin, but
different from that of the native enzyme, which uses a
terminal Fe(III)-bound nucleophile to initiate catalysis.
Binuclear Fe(III)Ni(II) biomimetics with coordination
environments similar to the coordination environment of
uteroferrin were generated to provide both experimental
benchmarks (structural and spectroscopic) and further
insight into the catalytic mechanism of hydrolysis. The
data are consistent with a reaction mechanism employing
an Fe(III)-bound terminal hydroxide as a nucleophile,
similar to that proposed for native uteroferrin and various
related isostructural biomimetics. Thus, only in the uteroferrin-
catalyzed reaction are the precise details of the
catalytic mechanism sensitive to the metal ion composition,
illustrating the significance of the dynamic ligand
environment in the protein active site for the optimization
of the catalytic efficiency
Thiosulfate sulfurtransferase prevents hyperglycemic damage to the zebrafish pronephros in an experimental model for diabetes
Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, was initially discovered as a cyanide detoxification enzyme. However, it was recently also found to be a genetic predictor of resistance to obesity-related type 2 diabetes. Diabetes type 2 is characterized by progressive loss of adequate β-cell insulin secretion and onset of insulin resistance with increased insulin demand, which contributes to the development of hyperglycemia. Diabetic complications have been replicated in adult hyperglycemic zebrafish, including retinopathy, nephropathy, impaired wound healing, metabolic memory, and sensory axonal degeneration. Pancreatic and duodenal homeobox 1 (Pdx1) is a key component in pancreas development and mature beta cell function and survival. Pdx1 knockdown or knockout in zebrafish induces hyperglycemia and is accompanied by organ alterations similar to clinical diabetic retinopathy and diabetic nephropathy. Here we show that pdx1-knockdown zebrafish embryos and larvae survived after incubation with thiosulfate and no obvious morphological alterations were observed. Importantly, incubation with hTST and thiosulfate rescued the hyperglycemic phenotype in pdx1-knockdown zebrafish pronephros. Activation of the mitochondrial TST pathway might be a promising option for therapeutic intervention in diabetes and its organ complications
A Planetary Microlensing Event with an Unusually Red Source Star: MOA-2011-BLG-291
We present the analysis of planetary microlensing event MOA-2011-BLG-291,
which has a mass ratio of and a source star that
is redder (or brighter) than the bulge main sequence. This event is located at
a low Galactic latitude in the survey area that is currently planned for NASA's
WFIRST exoplanet microlensing survey. This unusual color for a microlensed
source star implies that we cannot assume that the source star is in the
Galactic bulge. The favored interpretation is that the source star is a lower
main sequence star at a distance of kpc in the Galactic disk.
However, the source could also be a turn-off star on the far side of the bulge
or a sub-giant in the far side of the Galactic disk if it experiences
significantly more reddening than the bulge red clump stars. However, these
possibilities have only a small effect on our mass estimates for the host star
and planet. We find host star and planet masses of and from a Bayesian
analysis with a standard Galactic model under the assumption that the planet
hosting probability does not depend on the host mass or distance. However, if
we attempt to measure the host and planet masses with host star brightness
measurements from high angular resolution follow-up imaging, the implied masses
will be sensitive to the host star distance. The WFIRST exoplanet microlensing
survey is expected to use this method to determine the masses for many of the
planetary systems that it discovers, so this issue has important design
implications for the WFIRST exoplanet microlensing survey
Search for patterns by combining cosmic-ray energy and arrival directions at the Pierre Auger Observatory
Energy-dependent patterns in the arrival directions of cosmic rays are searched for using data of the Pierre Auger Observatory. We investigate local regions around the highest-energy cosmic rays with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}\end{document}E≥6×1019 eV by analyzing cosmic rays with energies above \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}\end{document}E≥5×1018 eV arriving within an angular separation of approximately 15\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}\end{document}∘. We characterize the energy distributions inside these regions by two independent methods, one searching for angular dependence of energy-energy correlations and one searching for collimation of energy along the local system of principal axes of the energy distribution. No significant patterns are found with this analysis. The comparison of these measurements with astrophysical scenarios can therefore be used to obtain constraints on related model parameters such as strength of cosmic-ray deflection and density of point sources
Prime Focus Spectrograph - Subaru's future -
The Prime Focus Spectrograph (PFS) of the Subaru Measurement of Images and
Redshifts (SuMIRe) project has been endorsed by Japanese community as one of
the main future instruments of the Subaru 8.2-meter telescope at Mauna Kea,
Hawaii. This optical/near-infrared multi-fiber spectrograph targets cosmology
with galaxy surveys, Galactic archaeology, and studies of galaxy/AGN evolution.
Taking advantage of Subaru's wide field of view, which is further extended with
the recently completed Wide Field Corrector, PFS will enable us to carry out
multi-fiber spectroscopy of 2400 targets within 1.3 degree diameter. A
microlens is attached at each fiber entrance for F-ratio transformation into a
larger one so that difficulties of spectrograph design are eased. Fibers are
accurately placed onto target positions by positioners, each of which consists
of two stages of piezo-electric rotary motors, through iterations by using
back-illuminated fiber position measurements with a wide-field metrology
camera. Fibers then carry light to a set of four identical fast-Schmidt
spectrographs with three color arms each: the wavelength ranges from 0.38
{\mu}m to 1.3 {\mu}m will be simultaneously observed with an average resolving
power of 3000. Before and during the era of extremely large telescopes, PFS
will provide the unique capability of obtaining spectra of 2400
cosmological/astrophysical targets simultaneously with an 8-10 meter class
telescope. The PFS collaboration, led by IPMU, consists of USP/LNA in Brazil,
Caltech/JPL, Princeton, & JHU in USA, LAM in France, ASIAA in Taiwan, and
NAOJ/Subaru.Comment: 13 pages, 11 figures, submitted to "Ground-based and Airborne
Instrumentation for Astronomy IV, Ian S. McLean, Suzanne K. Ramsay, Hideki
Takami, Editors, Proc. SPIE 8446 (2012)
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