275 research outputs found
Preprocessing 2D data for fast convex hull computations
No full text© 2019 Cadenas, Megson. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This paper presents a method to reduce a set of n 2D points to a smaller set of s 2D points with the property that the convex hull on the smaller set is the same as the convex hull of the original bigger set. The paper shows, experimentally, that such reduction accelerates computations; the time it takes to reduce from n down to s points plus the time of computing the convex hull on the s points is less than the time to compute the convex hull on the original set of n points. The method accepts 2D points expressed as real numbers and thus extends our previous method that required points as integers. The method achieves a percentage of reduction of points of over 90% in a collections of four datasets. This amount of reduction provides speedup factors of at least two for various common convex hull algorithms. Theoretically, the reduction method executes in time within O(n) and thus is suitable for preprocessing 2D data before computing the convex hull by any known algorithm
Macrophage phagocytosis of apoptotic neutrophils is critically regulated by the opposing actions of pro-inflammatory and anti-inflammatory agents: key role for tnf-α
No full textDevelopment of chronic inflammation or autoimmunity may be related
to deregulated mechanisms orchestrating successful resolution of inflammation,
especially apoptosis of inflammatory cells and their subsequent clearance by
macrophages (Mφ). Chronically inflamed sites are characterised by an excess of
the key pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and
importantly, TNF-α inhibitors, widely used in the clinical setting for the treatment
of rheumatoid arthritis (RA), inflammatory bowel disease and psoriasis,
significantly delay disease progression. TNF-α therefore may affect processes
implicated in resolution of inflammation. Although TNF-α and pro-inflammatory
bacterial products such as lipopolysaccharide (LPS) influence rates of
inflammatory cell apoptosis, little is known about their effects on Mφ
phagocytosis of apoptotic cells (efferocytosis). In this PhD thesis, the effects of
several pro-inflammatory agents (i.e., LPS, lipoteichoic acid (LTA),
peptidoglycan (PGN) and TNF-α) on efferocytosis by human blood monocytederived
Mφ (MDMφ) have been investigated. LPS, LTA and PGN all inhibited
MDMφ efferocytosis in a concentration- and time-dependent manner; however,
LPS did not inhibit the uptake of immunoglobulin-G (IgG)-opsonized
erythrocytes. Moreover, although TNF-α did inhibit efferocytosis, phagocytosis
of IgG-opsonized erythrocytes was not inhibited. Furthermore, the LPS effect
was attenuated by dimeric soluble human recombinant TNF receptor-1 (sTNFR1/
Fc), indicating a critical role of TNF-α. Concomitant treatments with
monomeric soluble human recombinant TNF receptor-1 (sTNF-R1) or the TNF-α
Converting Enzyme (TACE) inhibitor, TOPI-0, only partially reversed the
inhibitory effect of LPS.
Even though TNF-α release takes place within the first few hours
following LPS stimulation, the LPS-induced inhibitory effect occurred only if
treatment was performed for 96 hours or longer. Analysis of supernatants
obtained from LPS-treated MDMφ revealed that there appears to be interplay
between concentrations of TNF-α and interleukin-10 (IL-10) and that these
cytokines exert opposing actions on efferocytosis. IL-10 per se increased MDMφ
efferocytosis and addition of exogenous IL-10 to LPS-treated samples rescued phagocytosis. The latter effect was associated with the IL-10-induced,
concentration-dependent inhibition of TNF-α release. Interestingly, when IL-10
was added to TNF-α-treated MDMφ, only slight augmentation of phagocytosis
was observed. Furthermore, when IL-10-mediated effects were blocked by
concomitant treatment with anti-human IL-10 receptor 1 antibody (anti-IL-10-
R1Ab), the LPS inhibitory effect on phagocytosis was much greater and occurred
at 24 hours after treatment. The role of IL-10 on efferocytosis was also
investigated using IL-10 deficient murine bone marrow-derived Mφ (BMDMφ).
IL-10 deficient BMDMφ, when compared to wild-type, were characterised by a
much lower ability to phagocytose apoptotic neutrophils and this effect was
independent of culture conditions (control samples and LPS or TNF-α
treatments). Finally, effects of the synthetic steroid (dexamethasone) and nonsteroidal
anti-inflammatory drugs (NSAID) on MDMφ phagocytosis were
examined. Dexamethasone, like IL-10, augmented MDMφ efferocytosis, reversed
the inhibitory effects of both LPS and TNF-α, and suppressed LPS-induced
production of TNF-α. In contrast NSAID did not increase MDMφ efferocytosis
per se. However, preliminary data suggest that aspirin blocks the inhibitory effect
of TNF-α on phagocytosis.
In summary, it has been determined that prolonged treatment with proinflammatory
agents such as LPS, LTA and PGN inhibits MDMφ efferocytosis
which may potentially postpone the resolution of inflammation in vivo. I have
shown that TNF-α is a key mediator in this process and that IL-10 exerts an
important regulatory effect on TNF-α production and consequently on
efferocytosis. Furthermore, several approaches have been unveiled to
successfully reverse LPS-mediated inhibition of efferocytosis by decreasing
either TNF-α production or its inhibitory effect with sTNF-RI/Fc, exogenous IL-
10 or dexamethasone. These findings indicate that TNF-α and other agents which
influence efferocytosis may have significance in the resolution phase of
inflammation. In addition, presented findings provide important mechanistic
information into the potential mode of action of anti-TNF-α agents and steroids
and may help to explain their clinical success in the treatment of chronic
inflammatory diseases
A new class of NO-donor pro-drugs triggered by γ-glutamyl transpeptidase with potential for reno-selective vasodilatation
No full textThe authors are grateful to the Wellcome Trust (Catalyst Biomedica Development Award 063729/Z/01/Z) for financial support.This communication describes the synthesis of a new class of N-hydroxyguanidine (NHG) pro-drugs which release nitric oxide (NO), triggered by the action of gamma-glutamyl transpeptidase (gamma-GT), and have potential for the treatment of acute renal injury/failure (ARI/ARF).Peer reviewe
Screening for Intellectual Disability in Children: A Review of the Literature
No full textBACKGROUND: Early identification of possible intellectual disability can help children and families access appropriate services and support more quickly. There has been an increasing interest in the use of screening tools for this purpose. This study reviews the literature in relation to such tools.
METHODS: A literature search was carried out for English language articles from 1990 to 2009 using a range of databases. Secondary searches were carried out from references of relevant articles.
RESULTS: Only one article was identified which examined the ability of an assessment to specifically identify children with a potential intellectual disability; however, no information was provided about sensitivity, specificity or cut-off points.
CONCLUSIONS: There is not, as yet, a screening tool that can reliably identify children with a probable intellectual disability. Further research in this area is needed
Assessment of Polycyclic Aromatic Hydrocarbons in an Urban Soil Dataset
No full textWe compare a suite of Polycyclic Aromatic Hydrocarbons (Parent PAHs) in soils and air across an urban area (Belfast UK). Isomeric PAH ratios suggest that soil PAHs are mainly from a combustion source. Fugacity modelling across a range of soil temperatures predicts that four ring and larger PAHs from pyrene to indeno[1,2,3–cd]pyrene all partition strongly (>98%) to the soil compartment. This modelling also implies that these PAHs do not experience losses through partitioning to other phases (air, water) due to soil temperature effects. Such modelling may help in understanding the overall contaminantdistribution in soils. The air and soil data together with modelling suggests that care must be taken when considering isomeric ratios of compounds with mass lighter than 178 (i.e. phenanthrene and anthracene) in the soil phase. Comparison of duplicate and replicate samples suggest that field sampling of duplicates dominates uncertainty and validated methodologies for selection of field duplicates and lab splitting are required. As the urban soil four ring PAHs are at equilibrium in the soil phase, and have characteristic ratios that are dominated by a combustion source that is a single controlling factor over spatial distribution, methods that calculate background concentrations can be compared
Transputer implementation of systolic arrays for model reduction
No full textIn control theory the dynamics representing a physical system to be controlled is analyzed in terms of a model built up from a mathematical description of the system components. Unfortunately the resulting model can have high or infinite dimensional state equations, so it is often necessary from a practical and computational viewpoint to find a reduced model of the system which mimics closely the behaviour of the high order system. The technique for producing these simplified descriptions is termed model reduction and a number of methods are known. The author is interested in applying computational parallelism to the generation of reduced models to provide an acceleration mechanism for use in a CAD environment. In the paper the author develops systolic algorithms for simple single input-output control problems and implements them on a network of transputers. The performance of this network is then evaluated with respect to a sequential algorithm for the same problems. Finally, the author points out that systolic arrays are normally considered as special purpose methods geared towards exploiting VLSI techniques
Mapping a class of run-time dependencies onto regular arrays
No full textThe production of regular computations using algorithmic engineering techniques is beginning to play an important role in the synthesis of massively parallel and VLSI processor arrays. The author widens the class of algorithms that can be formally synthesized by introducing a mapping theorem for a class of algorithms with run-time dependencies. The technique is illustrated by deriving uniform recurrences for the so-called knapsack problem, the resulting systolic array is known to be optimal
Transputer Implementation of Systolic Arrays for Model Reduction
No full textIn the paper the author develops a unified bidirectional linear systolic array for performing model reduction of a feedback control system using continued fractions. The array is capable of computing the 1st, 2nd and 3rd Cauer forms of the fraction and their associated inverses as well as the Routh stability criterion. Timing graphs are presented to indicate the speed-up obtained on five transputers for common problem ranges
Antiinflammatory, gastrosparing and antiplatelet properties of new NO-donor esters of aspirin
No full textTransputer implementation of systolic arrays for model reduction
No full textThe author develops a unified bidirectional linear systolic array for performing model reduction of a feedback control system using continued fractions. The array is capable of computing the 1st, 2nd and 3rd Cauer forms of the fraction and their associated inverses as well as the Routh stability criterion. Timing graphs are presented to indicate the speed-up obtained on five transputers for common problem ranges
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