1,131 research outputs found
Anisotropic coarse-grained statistical potentials improve the ability to identify native-like protein structures
We present a new method to extract distance and orientation dependent
potentials between amino acid side chains using a database of protein
structures and the standard Boltzmann device. The importance of orientation
dependent interactions is first established by computing orientational order
parameters for proteins with alpha-helical and beta-sheet architecture.
Extraction of the anisotropic interactions requires defining local reference
frames for each amino acid that uniquely determine the coordinates of the
neighboring residues. Using the local reference frames and histograms of the
radial and angular correlation functions for a standard set of non-homologue
protein structures, we construct the anisotropic pair potentials. The
performance of the orientation dependent potentials was studied using a large
database of decoy proteins. The results demonstrate that the new distance and
orientation dependent residue-residue potentials present a significantly
improved ability to recognize native folds from a set of native and decoy
protein structures.Comment: Submitted to "The Journal of Chemical Physics
Blinking statistics of a molecular beacon triggered by end-denaturation of DNA
We use a master equation approach based on the Poland-Scheraga free energy
for DNA denaturation to investigate the (un)zipping dynamics of a denaturation
wedge in a stretch of DNA, that is clamped at one end. In particular, we
quantify the blinking dynamics of a fluorophore-quencher pair mounted within
the denaturation wedge. We also study the behavioural changes in the presence
of proteins, that selectively bind to single-stranded DNA. We show that such a
setup could be well-suited as an easy-to-implement nanodevice for sensing
environmental conditions in small volumes.Comment: 14 pages, 5 figures, LaTeX, IOP style. Accepted to J Phys Cond Mat
special issue on diffusio
Outcome of children with resistant and relapsed Hodgkin's disease.
During the period 1974-89, 169 children with Hodgkin's disease were treated in the Paediatric Oncology Units of the Royal Marsden and St Bartholomew's Hospitals. The overall actuarial survival for the whole group was 81% at 10 years. Thirty-five of the 169 children either did not achieve a complete remission or subsequently relapsed. The estimated actuarial survival from initial relapse or failure of primary treatment was 60% at 5 years and 45% at 10 years. Over half of the patients requiring salvage therapy had declared themselves within 2 years and only 3 relapses occurred more than 3 years from diagnosis. Very few patients remain disease free long term after failure of primary and initial salvage therapy. Patients relapsing within a year of diagnosis or not achieving a complete response to primary therapy and those with disseminated relapse had a poor response to salvage therapy. A significant subgroup of patients had prolonged survival despite multiple relapses. Neither initial histology nor stage affected survival from relapse although numbers in each subgroup were small
Observations and predictions at CesrTA, and outlook for ILC
In this paper, we will describe some of the recent experimental measurements
[1, 2, 3] performed at CESRTA [4], and the supporting simulations, which probe
the interaction of the electron cloud with the stored beam. These experiments
have been done over a wide range of beam energies, emittances, bunch currents,
and fill patterns, to gather sufficient information to be able to fully
characterize the beam-electron-cloud interaction and validate the simulation
programs. The range of beam conditions is chosen to be as close as possible to
those of the ILC damping ring, so that the validated simulation programs can be
used to predict the performance of these rings with regard to electroncloud-
related phenomena. Using the new simulation code Synrad3D to simulate the
synchrotron radiation environment, a vacuum chamber design has been developed
for the ILC damping ring which achieves the required level of photoelectron
suppression. To determine the expected electron cloud density in the ring, EC
buildup simulations have been done based on the simulated radiation environment
and on the expected performance of the ILC damping ring chamber mitigation
prescriptions. The expected density has been compared with analytical estimates
of the instability threshold, to verify that the ILC damping ring vacuum
chamber design is adequate to suppress the electron cloud single-bunch
head-tail instability.Comment: 11 pages, contribution to the Joint INFN-CERN-EuCARD-AccNet Workshop
on Electron-Cloud Effects: ECLOUD'12; 5-9 Jun 2012, La Biodola, Isola d'Elba,
Ital
Driven polymer translocation through a nanopore: a manifestation of anomalous diffusion
We study the translocation dynamics of a polymer chain threaded through a
nanopore by an external force. By means of diverse methods (scaling arguments,
fractional calculus and Monte Carlo simulation) we show that the relevant
dynamic variable, the translocated number of segments , displays an {\em
anomalous} diffusive behavior even in the {\em presence} of an external force.
The anomalous dynamics of the translocation process is governed by the same
universal exponent , where is the Flory
exponent and - the surface exponent, which was established recently
for the case of non-driven polymer chain threading through a nanopore. A closed
analytic expression for the probability distribution function , which
follows from the relevant {\em fractional} Fokker - Planck equation, is derived
in terms of the polymer chain length and the applied drag force . It is
found that the average translocation time scales as . Also the corresponding time dependent
statistical moments, and reveal unambiguously the anomalous nature of the translocation
dynamics and permit direct measurement of in experiments. These
findings are tested and found to be in perfect agreement with extensive Monte
Carlo (MC) simulations.Comment: 6 pages, 4 figures, accepted to Europhys. Lett; some references were
supplemented; typos were correcte
Directed motion emerging from two coupled random processes: Translocation of a chain through a membrane nanopore driven by binding proteins
We investigate the translocation of a stiff polymer consisting of M monomers
through a nanopore in a membrane, in the presence of binding particles
(chaperones) that bind onto the polymer, and partially prevent backsliding of
the polymer through the pore. The process is characterized by the rates: k for
the polymer to make a diffusive jump through the pore, q for unbinding of a
chaperone, and the rate q kappa for binding (with a binding strength kappa);
except for the case of no binding kappa=0 the presence of the chaperones give
rise to an effective force that drives the translocation process. Based on a
(2+1) variate master equation, we study in detail the coupled dynamics of
diffusive translocation and (partial) rectification by the binding proteins. In
particular, we calculate the mean translocation time as a function of the
various physical parameters.Comment: 22 pages, 5 figures, IOP styl
Advance care planning for patients with advanced illnesses attending hospital outpatient clinics study: A study protocol for a randomised controlled trial
© Author(s) (or their employer(s)) 2019. Introduction It is unclear whether advance care planning (ACP) undertaken with patients living in the community can improve patient care and avoid unwanted interventions and hospital admissions. We have designed a randomised controlled trial (RCT) to examine if ACP undertaken with patients with advanced illnesses attending hospital outpatient clinics can reduce unplanned hospital admissions and improve patient and caregiver well-being. Methods and analysis Pragmatic RCT involving patients from subspecialty outpatient clinics at five clinical sites in Sydney, Australia. Participants will be ≥18 years screened as potentially having palliative care needs and at risk of dying in 6-12 months. The patients will be randomised to intervention or control group. Intervention group will undertake ACP discussions facilitated by a trained health professional. The control group will receive written information on ACP, representing the current standard of care. The primary outcome is the number of unplanned hospital admissions at the 6-month follow-up. Secondary outcomes include: (i) patient's health-related quality-of-life and quality of chronic disease care; (ii) caregiver's health-related quality-of-life and caregiver burden and (iii) other health outcomes including ambulance usage, emergency department presentations, hospital admissions, resuscitation attempts, intensive care unit admissions, deaths, documentation of patient wishes in patient records and audit of ACP discussions and documents. The staff's self-reported attitudes and knowledge of ACP will also be measured. The data will be collected using self-report questionnaires, hospital records audit, audit of ACP documentation and data linkage analysis. Semistructured interviews and focus group discussions with patients, caregivers and healthcare professionals will explore the acceptability and feasibility of the intervention. Ethics and dissemination Approved by South-East Sydney Local Health District Human Research Ethics Committee and NSW Population and Health Services Research Ethics Committee. Results will be disseminated via conference presentations, journal publications, seminars and invited talks
Anomalous Dynamics of Translocation
We study the dynamics of the passage of a polymer through a membrane pore
(translocation), focusing on the scaling properties with the number of monomers
. The natural coordinate for translocation is the number of monomers on one
side of the hole at a given time. Commonly used models which assume Brownian
dynamics for this variable predict a mean (unforced) passage time that
scales as , even in the presence of an entropic barrier. However, the time
it takes for a free polymer to diffuse a distance of the order of its radius by
Rouse dynamics scales with an exponent larger than 2, and this should provide a
lower bound to the translocation time. To resolve this discrepancy, we perform
numerical simulations with Rouse dynamics for both phantom (in space dimensions
and 2), and self-avoiding (in ) chains. The results indicate that
for large , translocation times scale in the same manner as diffusion times,
but with a larger prefactor that depends on the size of the hole. Such scaling
implies anomalous dynamics for the translocation process. In particular, the
fluctuations in the monomer number at the hole are predicted to be
non-diffusive at short times, while the average pulling velocity of the polymer
in the presence of a chemical potential difference is predicted to depend on
.Comment: 9 pages, 9 figures. Submitted to Physical Review
SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale
Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role
- …