805 research outputs found
Mechanical testing of Additive Manufactured polymer components using Materials Extrusion Technology
Findings of the International Subarachnoid Aneurysm Trial and the National Study of Subarachnoid Haemorrhage in context.
Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding
The Shapes of Cooperatively Rearranging Regions in Glass Forming Liquids
The shapes of cooperatively rearranging regions in glassy liquids change from
being compact at low temperatures to fractal or ``stringy'' as the dynamical
crossover temperature from activated to collisional transport is approached
from below. We present a quantitative microscopic treatment of this change of
morphology within the framework of the random first order transition theory of
glasses. We predict a correlation of the ratio of the dynamical crossover
temperature to the laboratory glass transition temperature, and the heat
capacity discontinuity at the glass transition, Delta C_p. The predicted
correlation agrees with experimental results for the 21 materials compiled by
Novikov and Sokolov.Comment: 9 pages, 6 figure
Common sequence motifs of nascent chains engage the ribosome surface and trigger factor
In the cell, the conformations of nascent polypeptide chains during translation are modulated by both the ribosome and its associated molecular chaperone, trigger factor. The specific interactions that underlie these modulations, however, are still not known in detail. Here, we combine protein engineering, in-cell and in vitro NMR spectroscopy, and molecular dynamics simulations to explore how proteins interact with the ribosome during their biosynthesis before folding occurs. Our observations of α-synuclein nascent chains in living Escherichia coli cells reveal that ribosome surface interactions dictate the dynamics of emerging disordered polypeptides in the crowded cytosol. We show that specific basic and aromatic motifs drive such interactions and directly compete with trigger factor binding while biasing the direction of the nascent chain during its exit out of the tunnel. These results reveal a structural basis for the functional role of the ribosome as a scaffold with holdase characteristics and explain how handover of the nascent chain to specific auxiliary proteins occurs among a host of other factors in the cytosol
Identifying component modules
A computer-based system for modelling component dependencies and identifying component modules is presented. A variation of the Dependency Structure Matrix (DSM) representation was used to model component dependencies. The system utilises a two-stage approach towards facilitating the identification of a hierarchical modular structure. The first stage calculates a value for a clustering criterion that may be used to group component dependencies together. A Genetic Algorithm is described to optimise the order of the components within the DSM with the focus of minimising the value of the clustering criterion to identify the most significant component groupings (modules) within the product structure. The second stage utilises a 'Module Strength Indicator' (MSI) function to determine a value representative of the degree of modularity of the component groupings. The application of this function to the DSM produces a 'Module Structure Matrix' (MSM) depicting the relative modularity of available component groupings within it. The approach enabled the identification of hierarchical modularity in the product structure without the requirement for any additional domain specific knowledge within the system. The system supports design by providing mechanisms to explicitly represent and utilise component and dependency knowledge to facilitate the nontrivial task of determining near-optimal component modules and representing product modularity
Interpolating the Sherrington-Kirkpatrick replica trick
The interpolation techniques have become, in the past decades, a powerful
approach to lighten several properties of spin glasses within a simple
mathematical framework. Intrinsically, for their construction, these schemes
were naturally implemented into the cavity field technique, or its variants as
the stochastic stability or the random overlap structures. However the first
and most famous approach to mean field statistical mechanics with quenched
disorder is the replica trick. Among the models where these methods have been
used (namely, dealing with frustration and complexity), probably the best known
is the Sherrington-Kirkpatrick spin glass: In this paper we are pleased to
apply the interpolation scheme to the replica trick framework and test it
directly to the cited paradigmatic model: interestingly this allows to obtain
easily the replica-symmetric control and, synergically with the broken replica
bounds, a description of the full RSB scenario, both coupled with several minor
theorems. Furthermore, by treating the amount of replicas as an
interpolating parameter (far from its original interpretation) this can be
though of as a quenching temperature close to the one introduce in
off-equilibrium approaches and, within this viewpoint, the proof of the
attended commutativity of the zero replica and the infinite volume limits can
be obtained.Comment: This article is dedicated to David Sherrington on the occasion of his
seventieth birthda
Severe traumatic injury during long duration spaceflight: Light years beyond ATLS
Traumatic injury strikes unexpectedly among the healthiest members of the human population, and has been an inevitable companion of exploration throughout history. In space flight beyond the Earth's orbit, NASA considers trauma to be the highest level of concern regarding the probable incidence versus impact on mission and health. Because of limited resources, medical care will have to focus on the conditions most likely to occur, as well as those with the most significant impact on the crew and mission. Although the relative risk of disabling injuries is significantly higher than traumatic deaths on earth, either issue would have catastrophic implications during space flight. As a result this review focuses on serious life-threatening injuries during space flight as determined by a NASA consensus conference attended by experts in all aspects of injury and space flight
CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial
Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure
to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched,
with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted
treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need
to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.
Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in
the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336
patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be
recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to
epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min
intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab
increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free
survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed
according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and
for other time-to-event endpoints).
Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab
in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely
to become the new standard of care in the UK
Detection of hidden structures for arbitrary scales in complex physical systems
Recent decades have experienced the discovery of numerous complex materials. At the root of the complexity underlying many of these materials lies a large number of contending atomic- and largerscale configurations. In order to obtain a more detailed understanding of such systems, we need tools that enable the detection of pertinent structures on all spatial and temporal scales. Towards this end, we suggest a new method that applies to both static and dynamic systems which invokes ideas from network analysis and information theory. Our approach efficiently identifies basic unit cells, topological defects, and candidate natural structures. The method is particularly useful where a clear definition of order is lacking, and the identified features may constitute a natural point of departure for further analysis
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