4,714 research outputs found
Structure and function of proteins and nucleic acid Progress report, 1 Jul. - 31 Dec. 1967
Conformation of pyridine nucleotide coenzymes by rotary dispersion and dichrois
A Fluorescent Probe at the Active Site of Alpha Chymotrypsin
Spectrofluorimetric analysis of mobility and polarity of active sites of alpha chymotrypsi
Assessing the impact of England's National Health Service R&D Health Technology Assessment program using the "payback" approach
Copyright © Cambridge University Press 2009Objectives: This study assesses the impact of the English National Health Service (NHS) Health Technology Assessment (HTA) program using the "payback" framework.Methods: A survey of lead investigators of all research projects funded by the HTA program 1993-2003 supplemented by more detailed case studies of sixteen projects.Results: Of 204 eligible projects, replies were received from 133 or 65 percent. The mean number of peer-reviewed publications per project was 2.9. Seventy-three percent of projects claimed to have had had an impact on policy and 42 percent on behavior. Technology Assessment Reports for the National Institute for Health and Clinical Excellence (NICE) had fewer than average publications but greater impact on policy. Half of all projects went on to secure further funding. The case studies confirmed the survey findings and indicated factors associated with impact.Conclusions: The HTA program performed relatively well in terms of "payback." Facilitating factors included the program's emphasis on topics that matter to the NHS, rigorous methods and the existence of "policy customers" such as NICE
Mean field approaches to the totally asymmetric exclusion process with quenched disorder and large particles
The process of protein synthesis in biological systems resembles a one
dimensional driven lattice gas in which the particles (ribosomes) have spatial
extent, covering more than one lattice site. Realistic, nonuniform gene
sequences lead to quenched disorder in the particle hopping rates. We study the
totally asymmetric exclusion process with large particles and quenched disorder
via several mean field approaches and compare the mean field results with Monte
Carlo simulations. Mean field equations obtained from the literature are found
to be reasonably effective in describing this system. A numerical technique is
developed for computing the particle current rapidly. The mean field approach
is extended to include two-point correlations between adjacent sites. The
two-point results are found to match Monte Carlo simulations more closely
Structurally specific thermal fluctuations identify functional sites for DNA transcription
We report results showing that thermally-induced openings of double stranded
DNA coincide with the location of functionally relevant sites for
transcription. Investigating both viral and bacterial DNA gene promoter
segments, we found that the most probable opening occurs at the transcription
start site. Minor openings appear to be related to other regulatory sites. Our
results suggest that coherent thermal fluctuations play an important role in
the initiation of transcription. Essential elements of the dynamics, in
addition to sequence specificity, are nonlinearity and entropy, provided by
local base-pair constraints
Multi-site H-bridge breathers in a DNA--shaped double strand
We investigate the formation process of nonlinear vibrational modes
representing broad H-bridge multi--site breathers in a DNA--shaped double
strand.
Within a network model of the double helix we take individual motions of the
bases within the base pair plane into account. The resulting H-bridge
deformations may be asymmetric with respect to the helix axis. Furthermore the
covalent bonds may be deformed distinctly in the two backbone strands.
Unlike other authors that add different extra terms we limit the interaction
to the hydrogen bonds within each base pair and the covalent bonds along each
strand. In this way we intend to make apparent the effect of the characteristic
helicoidal structure of DNA. We study the energy exchange processes related
with the relaxation dynamics from a non-equilibrium conformation. It is
demonstrated that the twist-opening relaxation dynamics of a radially distorted
double helix attains an equilibrium regime characterized by a multi-site
H-bridge breather.Comment: 27 pages and 10 figure
Highly Designable Protein Structures and Inter Monomer Interactions
By exact computer enumeration and combinatorial methods, we have calculated
the designability of proteins in a simple lattice H-P model for the protein
folding problem.
We show that if the strength of the non-additive part of the interaction
potential becomes larger than a critical value, the degree of designability of
structures will depend on the parameters of potential. We also show that the
existence of a unique ground state is highly sensitive to mutation in certain
sites.Comment: 14 pages, Latex file, 3 latex and 6 eps figures are include
Imaging density disturbances in water with 41.3 attosecond time resolution
We show that the momentum flexibility of inelastic x-ray scattering may be
exploited to invert its loss function, alowing real time imaging of density
disturbances in a medium. We show the disturbance arising from a point source
in liquid water, with a resolution of 41.3 attoseconds (
sec) and 1.27 ( cm). This result is used to
determine the structure of the electron cloud around a photoexcited molecule in
solution, as well as the wake generated in water by a 9 MeV gold ion. We draw
an analogy with pump-probe techniques and suggest that energy-loss scattering
may be applied more generally to the study of attosecond phenomena.Comment: 4 pages, 4 color figure
Thermodynamic and Kinetic Analysis of Sensitivity Amplification in Biological Signal Transduction
Based on a thermodynamic analysis of the kinetic model for the protein
phosphorylation-dephosphorylation cycle, we study the ATP (or GTP) energy
utilization of this ubiquitous biological signal transduction process. It is
shown that the free energy from hydrolysis inside cells,
(phosphorylation potential), controls the amplification and sensitivity of the
switch-like cellular module; the response coefficient of the sensitivity
amplification approaches the optimal 1 and the Hill coefficient increases with
increasing . We discover that zero-order ultrasensitivity is
mathematically equivalent to allosteric cooperativity. Furthermore, we show
that the high amplification in ultrasensitivity is mechanistically related to
the proofreading kinetics for protein biosynthesis. Both utilize multiple
kinetic cycles in time to gain temporal cooperativity, in contrast to
allosteric cooperativity that utilizes multiple subunits in a protein.Comment: 19 pages, 7 figure
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