592 research outputs found
Tensor Perturbations in Quantum Cosmological Backgrounds
In the description of the dynamics of tensor perturbations on a homogeneous
and isotropic background cosmological model, it is well known that a simple
Hamiltonian can be obtained if one assumes that the background metric satisfies
Einstein classical field equations. This makes it possible to analyze the
quantum evolution of the perturbations since their dynamics depends only on
this classical background. In this paper, we show that this simple Hamiltonian
can also be obtained from the Einstein-Hilbert lagrangian without making use of
any assumption about the dynamics of the background metric. In particular, it
can be used in situations where the background metric is also quantized, hence
providing a substantial simplification over the direct approach originally
developed by Halliwell and Hawking.Comment: 24 pages, JHEP forma
The ELAV RNA-stability factor HuR binds the 5′-untranslated region of the human IGF-IR transcript and differentially represses cap-dependent and IRES-mediated translation
The type I insulin-like growth factor receptor (IGF-IR) is an integral component in the control of cell proliferation, differentiation and apoptosis. The IGF-IR mRNA contains an extraordinarily long (1038 nt) 5′-untranslated region (5′-UTR), and we have characterized a diverse series of proteins interacting with this RNA sequence which may provide for intricate regulation of IGF-IR gene expression at the translational level. Here, we report the purification and identification of one of these IGF-IR 5′-UTR-binding proteins as HuR, using a novel RNA crosslinking/RNase elution strategy. Because HuR has been predominantly characterized as a 3′-UTR-binding protein, enhancing mRNA stability and generally increasing gene expression, we sought to determine whether HuR might serve a different function in the context of its binding the IGF-IR 5′-UTR. We found that HuR consistently repressed translation initiation through the IGF-IR 5′-UTR. The inhibition of translation by HuR was concentration dependent, and could be reversed in trans by addition of a fragment of the IGF-IR 5′-UTR containing the HuR binding sites as a specific competitor, or abrogated by deletion of the third RNA recognition motif of HuR. We determined that HuR repressed translation initiation through the IGF-IR 5′-UTR in cells as well, and that siRNA knockdown of HuR markedly increased IGF-IR protein levels. Interestingly, we also found that HuR potently inhibited IGF-IR translation mediated through internal ribosome entry. Kinetic assays were performed to investigate the mechanism of translation repression by HuR and the dynamic interplay between HuR and the translation apparatus. We found that HuR, occupying a cap-distal position, significantly delayed translation initiation mediated by cap-dependent scanning, but was eventually displaced from its binding site, directly or indirectly, as a consequence of ribosomal scanning. However, HuR perpetually blocked the activity of the IGF-IR IRES, apparently arresting the IRES-associated translation pre-initiation complex in an inactive state. This function of HuR as a 5′-UTR-binding protein and dual-purpose translation repressor may be critical for the precise regulation of IGF-IR expression essential to normal cellular homeostasis
Looking Ahead: Addressing Ethical Challenges in Public Health Practice
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75478/1/j.1748-720X.2007.00188.x.pd
Pruning the regulatory tree
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62897/1/457534a.pd
I-BEAT: New ultrasonic method for single bunch measurement of ion energy distribution
The shape of a wave carries all information about the spatial and temporal
structure of its source, given that the medium and its properties are known.
Most modern imaging methods seek to utilize this nature of waves originating
from Huygens' principle. We discuss the retrieval of the complete kinetic
energy distribution from the acoustic trace that is recorded when a short ion
bunch deposits its energy in water. This novel method, which we refer to as
Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a generalization of the
ionoacoustic approach. Featuring compactness, simple operation,
indestructibility and high dynamic ranges in energy and intensity, I-BEAT is a
promising approach to meet the needs of petawatt-class laser-based ion
accelerators. With its capability of completely monitoring a single, focused
proton bunch with prompt readout it, is expected to have particular impact for
experiments and applications using ultrashort ion bunches in high flux regimes.
We demonstrate its functionality using it with two laser-driven ion sources for
quantitative determination of the kinetic energy distribution of single,
focused proton bunches.Comment: Paper: 17 Pages, 3 figures Supplementary Material 16 pages, 7 figure
Dynamical mean-field theory for bosons
We discuss the recently developed bosonic dynamical mean-field (B-DMFT)
framework, which maps a bosonic lattice model onto the selfconsistent solution
of a bosonic impurity model with coupling to a reservoir of normal and
condensed bosons. The effective impurity action is derived in several ways: (i)
as an approximation to the kinetic energy functional of the lattice problem,
(ii) using a cavity approach, and (iii) by using an effective medium approach
based on adding a one-loop correction to the selfconsistently defined
condensate. To solve the impurity problem, we use a continuous-time Monte Carlo
algorithm based on a sampling of a perturbation expansion in the hybridization
functions and the condensate wave function. As applications of the formalism we
present finite temperature B-DMFT phase diagrams for the bosonic Hubbard model
on a 3d cubic and 2d square lattice, the condensate order parameter as a
function of chemical potential, critical exponents for the condensate, the
approach to the weakly interacting Bose gas regime for weak repulsions, and the
kinetic energy as a function of temperature.Comment: 26 pages, 19 figure
Addressing conflicts of interest in Public Private Partnerships
<p>Abstract</p> <p>Background</p> <p>Many articles have been written on conflicts of interests (COIs) in fields such as medicine, business, politics, public service and education. With the growing abundance of Public Private Partnerships (PPPs), often involving complex relationships among the partners, it is important to understand how COIs can be mitigated and managed in PPPs.</p> <p>Discussion</p> <p>We wanted to study PPPs, particularly in the areas of global health and agriculture, but discovered no single source of information available to identify and compare various approaches for avoiding and managing COIs in PPPs. This is a significant gap, especially for those wishing to study, compare and strengthen existing COI policies related to PPPs. In order to bridge this gap, we reviewed how PPPs currently address COIs and highlight what might be considered good practice in developing COI policies. We reviewed the online COI policies of 10 PPPs in global health and agriculture, and interviewed two global health PPP chief executives.</p> <p>Summary</p> <p>Based on our review of policies and interviews, we conclude that there exists a range of good practices including attention to accountability and governance, acknowledgement and disclosure, abstention and withdrawal, reporting and transparency, and independent monitoring. There appears to be a need for PPPs to interact closely and learn from each other on these parameters and to also place more emphasis on independent external monitoring of COIs as a means of strengthening their major social objectives on which their activities are largely predicated. We also recommend the establishment of a web based database, which would serve as a forum to discuss COI issues and how they can be resolved.</p
Evaluation of Handheld Assays for the Detection of Ricin and Staphylococcal Enterotoxin B in Disinfected Waters
Development of a rapid field test is needed capable of determining if field supplies of water are safe to drink by the warfighter during a military operation. The present study sought to assess the effectiveness of handheld assays (HHAs) in detecting ricin and Staphylococcal Enterotoxin B (SEB) in water. Performance of HHAs was evaluated in formulated tap water with and without chlorine, reverse osmosis water (RO) with chlorine, and RO with bromine. Each matrix was prepared, spiked with ricin or SEB at multiple concentrations, and then loaded onto HHAs. HHAs were allowed to develop and then read visually. Limits of detection (LOD) were determined for all HHAs in each water type. Both ricin and SEB were detected by HHAs in formulated tap water at or below the suggested health effect levels of 455 ng/mL and 4.55 ng/mL, respectively. However, in brominated or chlorinated waters, LODs for SEB increased to approximately 2,500 ng/mL. LODs for ricin increased in chlorinated water, but still remained below the suggested health effect level. In brominated water, the LOD for ricin increased to approximately 2,500 ng/mL. In conclusion, the HHAs tested were less effective at detecting ricin and SEB in disinfected water, as currently configured
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