947 research outputs found
A pragmatic approach to semantic repositories benchmarking
The aim of this paper is to benchmark various semantic repositories in order to evaluate their deployment in a commercial image retrieval and browsing application. We adopt a two-phase approach for evaluating the target semantic repositories: analytical parameters such as query language and reasoning support are used to select the pool of the target repositories, and practical parameters such as load and query response times are used to select the best match to application requirements. In addition to utilising a widely accepted benchmark for OWL repositories (UOBM), we also use a real-life dataset from the target application, which provides us with the opportunity of consolidating our findings. A distinctive advantage of this benchmarking study is that the essential requirements for the target system such as the semantic expressivity and data scalability are clearly defined, which allows us to claim contribution to the benchmarking methodology for this class of applications
Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates
The presence of oligomeric aggregates, which is often observed during the
process of amyloid formation, has recently attracted much attention since it
has been associated with neurodegenerative conditions such as Alzheimer's and
Parkinson's diseases. We provide a description of a sequence-indepedent
mechanism by which polypeptide chains aggregate by forming metastable
oligomeric intermediate states prior to converting into fibrillar structures.
Our results illustrate how the formation of ordered arrays of hydrogen bonds
drives the formation of beta-sheets within the disordered oligomeric aggregates
that form early under the effect of hydrophobic forces. Initially individual
beta-sheets form with random orientations, which subsequently tend to align
into protofilaments as their lengths increases. Our results suggest that
amyloid aggregation represents an example of the Ostwald step rule of first
order phase transitions by showing that ordered cross-beta structures emerge
preferentially from disordered compact dynamical intermediate assemblies.Comment: 14 pages, 4 figure
Recognizing and Drawing IC-planar Graphs
IC-planar graphs are those graphs that admit a drawing where no two crossed
edges share an end-vertex and each edge is crossed at most once. They are a
proper subfamily of the 1-planar graphs. Given an embedded IC-planar graph
with vertices, we present an -time algorithm that computes a
straight-line drawing of in quadratic area, and an -time algorithm
that computes a straight-line drawing of with right-angle crossings in
exponential area. Both these area requirements are worst-case optimal. We also
show that it is NP-complete to test IC-planarity both in the general case and
in the case in which a rotation system is fixed for the input graph.
Furthermore, we describe a polynomial-time algorithm to test whether a set of
matching edges can be added to a triangulated planar graph such that the
resulting graph is IC-planar
Fibril elongation mechanisms of HET-s prion-forming domain: Topological evidence for growth polarity
The prion-forming C-terminal domain of the fungal prion HET-s forms
infectious amyloid fibrils at physiological pH. The conformational switch from
the non-prion soluble form to the prion fibrillar form is believed to have a
functional role, since HET-s in its prion form participates in a recognition
process of different fungal strains. Based on the knowledge of the
high-resolution structure of HET-s(218-289) (the prion forming-domain) in its
fibrillar form, we here present a numerical simulation of the fibril growth
process which emphasizes the role of the topological properties of the
fibrillar structure. An accurate thermodynamic analysis of the way an
intervening HET-s chain is recruited to the tip of the growing fibril suggests
that elongation proceeds through a dock and lock mechanism. First, the chain
docks onto the fibril by forming the longest -strands. Then, the
re-arrangement in the fibrillar form of all the rest of molecule takes place.
Interestingly, we predict also that one side of the HET-s fibril is more
suitable for substaining its growth with respect to the other. The resulting
strong polarity of fibril growth is a consequence of the complex topology of
HET-s fibrillar structure, since the central loop of the intervening chain
plays a crucially different role in favouring or not the attachment of the
C-terminus tail to the fibril, depending on the growth side.Comment: 16 pages, 10 figure
A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation
Nanoparticles introduced in living cells are capable of strongly promoting
the aggregation of peptides and proteins. We use here molecular dynamics
simulations to characterise in detail the process by which nanoparticle
surfaces catalyse the self- assembly of peptides into fibrillar structures. The
simulation of a system of hundreds of peptides over the millisecond timescale
enables us to show that the mechanism of aggregation involves a first phase in
which small structurally disordered oligomers assemble onto the nanoparticle
and a second phase in which they evolve into highly ordered beta-sheets as
their size increases
Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells
Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes
Post-coital intra-cerebral venous hemorrhage in a 78-year-old man with jugular valve incompetence: a case report
<p>Abstract</p> <p>Introduction</p> <p>Spontaneous intra-cerebral hemorrhage can occur in patients with venous disease due to obstructed venous outflow.</p> <p>Case presentation</p> <p>We report the case of a 78-year-old Caucasian man with jugular valve incompetence who experienced an intra-cerebral temporo-occipital hemorrhage following sexual intercourse. He had no other risk factors for an intra-cerebral hemorrhage.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first case of intra-cerebral hemorrhage due to jugular valve incompetence in association with the physical exertion associated with sexual intercourse.</p
Minimally invasive surgery treatment for the patients with spontaneous supratentorial intracerebral hemorrhage (MISTICH): protocol of a multi-center randomized controlled trial
The Effect of Diagnostic Delays on the Drop-Out Rate and the Total Delay to Diagnosis of Tuberculosis
Background: Numerous patient and healthcare system-related delays contribute to the overall delay experienced by patients from onset of TB symptoms to diagnosis and treatment. Such delays are critical as infected individuals remain untreated in the community, providing more opportunities for transmission of the disease and adversely affecting the epidemic. Methodology/Principal Findings: We present an analysis of the factors that contribute to the overall delay in TB diagnosis and treatment, in a resource-poor setting. Impact on the distribution of diagnostic delay times was assessed for various factors, the sensitivity of the diagnostic method being found to be the most significant. A linear relationship was found between the sensitivity of the test and the predicted mean delay time, with an increase in test sensitivity resulting in a reduced mean delay time and a reduction in the drop-out rate. Conclusions/Significance: The results show that in a developing country a number of delay factors, particularly the low sensitivity of the initial sputum smear microscopy test, potentially increase total diagnostic delay times experienced by TB patients significantly. The results reinforce the urgent need for novel diagnostic methods, both for smear positive an
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