3,986 research outputs found
Advances in precision medicine: tailoring individualised therapies
The traditional bench-to-bedside pipeline involves using model systems and patient samples to provide insights into pathways deregulated in cancer. This discovery reveals new biomarkers and therapeutic targets, ultimately stratifying patients and informing cohort-based treatment options. Precision medicine (molecular profiling of individual tumors combined with established clinical-pathological parameters) reveals, in real-time, individual patient's diagnostic and prognostic risk profile, informing tailored and tumor-specific treatment plans. Here we discuss advances in precision medicine presented at the Irish Association for Cancer Research Annual Meeting, highlighting examples where personalized medicine approaches have led to precision discovery in individual tumors, informing customized treatment programs
Local field enhancement: comparing self-similar and dimer nanoantennas
We study the local field enhancement properties of self-similar nanolenses
and compare the obtained results with the performance of standard dimer
nanoantennas. We report that, despite the additional structural complexity,
self-similar nanolenses are unable to provide significant improvements over the
field enhancement performance of standard plasmonic dimers
Protein folding in high-dimensional spaces:hypergutters and the role of non-native interactions
We explore the consequences of very high dimensionality in the dynamical
landscape of protein folding. Consideration of both typical range of
stabilising interactions, and folding rates themselves, leads to a model of the
energy hypersurface that is characterised by the structure of diffusive
"hypergutters" as well as the familiar "funnels". Several general predictions
result: (1) intermediate subspaces of configurations will always be visited;
(2) specific but non-native interactions are important in stabilising these
low-dimensional diffusive searches on the folding pathway; (3) sequential
barriers will commonly be found, even in "two-state"proteins; (4) very early
times will show charactreristic departures from single-exponential kinetics;
(5) contributions of non-native interactions to phi-values are calculable, and
may be significant. The example of a three-helix bundle is treated in more
detail as an illustration. The model also shows that high-dimensional
structures provide conceptual relations between the "folding funnel",
"diffusion-collision", "nucleation-condensation" and "topomer search" models of
protein folding. It suggests that kinetic strategies for fast folding may be
encoded rather generally in non-native, rather than native interactions. The
predictions are related to very recent findings in experiment and simulation.Comment: Submitted to Biophys.
Unfolding dynamics of proteins under applied force
Understanding the mechanisms of protein folding is a major challenge that is being addressed effectively by collaboration between researchers in the physical and life sciences. Recently, it has become possible to mechanically unfold proteins by pulling on their two termini using local force probes such as the atomic force microscope. Here, we present data from experiments in which synthetic protein polymers designed to mimic naturally occurring polyproteins have been mechanically unfolded. For many years protein folding dynamics have been studied using chemical denaturation, and we therefore firstly discuss our mechanical unfolding data in the context of such experiments and show that the two unfolding mechanisms are not the same, at least for the proteins studied here. We also report unexpected observations that indicate a history effect in the observed unfolding forces of polymeric proteins and explain this in terms of the changing number of domains remaining to unfold and the increasing compliance of the lengthening unstructured polypeptide chain produced each time a domain unfolds
Exploring multiple viewshed analysis using terrain features and optimisation techniques
The calculation of viewsheds is a routine operation in geographic information systems and is used in a wide range of applications. Many of these involve the siting of features, such as radio masts, which are part of a network and yet the selection of sites is normally done separately for each feature. The selection of a series of locations which collectively maximise the visual coverage of an area is a combinatorial problem and as such cannot be directly solved except for trivial cases. In this paper, two strategies for tackling this problem are explored. The first is to restrict the search to key topographic points in the landscape such as peaks, pits and passes. The second is to use heuristics which have been applied to other maximal coverage spatial problems such as location-allocation. The results show that the use of these two strategies results in a reduction of the computing time necessary by two orders of magnitude, but at the cost of a loss of 10% in the area viewed. Three different heuristics were used, of which Simulated Annealing produced the best results. However the improvement over a much simpler fast-descent swap heuristic was very slight, but at the cost of greatly increased running times. © 2004 Elsevier Ltd. All rights reserved
A network approach for managing and processing big cancer data in clouds
Translational cancer research requires integrative analysis of multiple levels of big cancer data to identify and treat cancer. In order to address the issues that data is decentralised, growing and continually being updated, and the content living or archiving on different information sources partially overlaps creating redundancies as well as contradictions and inconsistencies, we develop a data network model and technology for constructing and managing big cancer data. To support our data network approach for data process and analysis, we employ a semantic content network approach and adopt the CELAR cloud platform. The prototype implementation shows that the CELAR cloud can satisfy the on-demanding needs of various data resources for management and process of big cancer data
EIF1AX c.338-2A>T splice site mutation in a patient with trabecular adenoma and cytological indeterminate lesion
SUMMARY The EIF1AX gene mutations have been recently associated with papillary thyroid carcinoma and anaplastic thyroid cancer. According with these reports, the gene as been considered as a drive gene for thyroid cancer development. However, the occurrence of these alterations in benign thyroid lesions is not known and is still under investigation. Some authors have already reported the presence of EIF1AX variants in follicular adenomas and hyperplastic nodules. Here, we describe for the first time a case of a man with the EIF1AX c.338-2A>T splice site mutation in an indeterminate FNA lesion with trabecular adenoma at final histology in the absence of other pathogenetic mutations, demonstrating that further studies are required to better understand EIF1AX role in the tumorigenesis of thyroid carcinoma
State-of-the-art in aerodynamic shape optimisation methods
Aerodynamic optimisation has become an indispensable component for any aerodynamic design over the past 60 years, with applications to aircraft, cars, trains, bridges, wind turbines, internal pipe flows, and cavities, among others, and is thus relevant in many facets of technology. With advancements in computational power, automated design optimisation procedures have become more competent, however, there is an ambiguity and bias throughout the literature with regards to relative performance of optimisation architectures and employed algorithms. This paper provides a well-balanced critical review of the dominant optimisation approaches that have been integrated with aerodynamic theory for the purpose of shape optimisation. A total of 229 papers, published in more than 120 journals and conference proceedings, have been classified into 6 different optimisation algorithm approaches. The material cited includes some of the most well-established authors and publications in the field of aerodynamic optimisation. This paper aims to eliminate bias toward certain algorithms by analysing the limitations, drawbacks, and the benefits of the most utilised optimisation approaches. This review provides comprehensive but straightforward insight for non-specialists and reference detailing the current state for specialist practitioners
The Interplay between Chemistry and Mechanics in the Transduction of a Mechanical Signal into a Biochemical Function
There are many processes in biology in which mechanical forces are generated.
Force-bearing networks can transduce locally developed mechanical signals very
extensively over different parts of the cell or tissues. In this article we
conduct an overview of this kind of mechanical transduction, focusing in
particular on the multiple layers of complexity displayed by the mechanisms
that control and trigger the conversion of a mechanical signal into a
biochemical function. Single molecule methodologies, through their capability
to introduce the force in studies of biological processes in which mechanical
stresses are developed, are unveiling subtle intertwining mechanisms between
chemistry and mechanics and in particular are revealing how chemistry can
control mechanics. The possibility that chemistry interplays with mechanics
should be always considered in biochemical studies.Comment: 50 pages, 18 figure
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