Showing papers by "Trinity College, Dublin published in 2004"
TL;DR: Lynch et al. as mentioned in this paper identified the cellular and molecu... cellular and memory cells in neuroscience is one of the most significant challenges in neuroscience and identified the most important genes for long-term potentiation and memory.
Abstract: Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecu...
1,683 citations
TL;DR: This review is intended to sum up the present understanding of the events following LPS binding to TLR4, and to create a model of the signalling pathways activated by LPS.
Abstract: An understanding of lipopolysaccharide (LPS) signal transduction is a key goal in the effort to provide a molecular basis for the lethal effect of LPS during septic shock and point the way to novel therapies. Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS - Toll-like receptor 4 (TLR4) - but also in a better appreciation of the complexity of the signalling pathways activated by LPS. Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD-2, was described. Intracellular events following the formation of this receptor complex depend on different sets of adapters. An early response, which is dependent on MyD88 and MyD88-like adapter (Mal), leads to the activation of nuclear factor-kappaB (NF-kappaB). A later response to LPS makes use of TIR-domain-containing adapter-inducing interferon-beta (TRIF) and TRIF-related adapter molecule (TRAM), and leads to the late activation of NF-kappaB and IRF3, and to the induction of cytokines, chemokines, and other transcription factors. As LPS signal transduction is an area of intense research and rapid progress, this review is intended to sum up our present understanding of the events following LPS binding to TLR4, and we also attempt to create a model of the signalling pathways activated by LPS.
1,171 citations
TL;DR: The unusual age profile of tandem gene duplications in Arabidopsis indicates that other scenarios, such as variation in the rate at which duplicated genes are deleted, must also be considered.
Abstract: It is often anticipated that many of today’s diploid plant species are in fact paleopolyploids. Given that an ancient large-scale duplication will result in an excess of relatively old duplicated genes with similar ages, we analyzed the timing of duplication of pairs of paralogous genes in 14 model plant species. Using EST contigs (unigenes), we identified pairs of paralogous genes in each species and used the level of synonymous nucleotide substitution to estimate the relative ages of gene duplication. For nine of the investigated species (wheat [Triticum aestivum], maize [Zea mays], tetraploid cotton [Gossypium hirsutum], diploid cotton [G. arboretum], tomato [Lycopersicon esculentum], potato [Solanum tuberosum], soybean [Glycine max], barrel medic [Medicago truncatula], and Arabidopsis thaliana), the age distributions of duplicated genes contain peaks corresponding to short evolutionary periods during which large numbers of duplicated genes were accumulated. Large-scale duplications (polyploidy or aneuploidy) are strongly suspected to be the cause of these temporal peaks of gene duplication. However, the unusual age profile of tandem gene duplications in Arabidopsis indicates that other scenarios, such as variation in the rate at which duplicated genes are deleted, must also be considered.
1,123 citations
TL;DR: Functional diversification of the surviving duplicated genes is a major feature of the long-term evolution of polyploidy, and the rate of protein sequence evolution has been significantly asymmetric in >20% of duplicate pairs.
Abstract: To study the evolutionary effects of polyploidy on plant gene functions, we analyzed functional genomics data for a large number of duplicated gene pairs formed by ancient polyploidy events in Arabidopsis thaliana. Genes retained in duplicate are not distributed evenly among Gene Ontology or Munich Information Center for Protein Sequences functional categories, which indicates a nonrandom process of gene loss. Genes involved in signal transduction and transcription have been preferentially retained, and those involved in DNA repair have been preferentially lost. Although the two members of each gene pair must originally have had identical transcription profiles, less than half of the pairs formed by the most recent polyploidy event still retain significantly correlated profiles. We identified several cases where groups of duplicated gene pairs have diverged in concert, forming two parallel networks, each containing one member of each gene pair. In these cases, the expression of each gene is strongly correlated with the other nonhomologous genes in its network but poorly correlated with its paralog in the other network. We also find that the rate of protein sequence evolution has been significantly asymmetric in >20% of duplicate pairs. Together, these results suggest that functional diversification of the surviving duplicated genes is a major feature of the long-term evolution of polyploids.
1,048 citations
TL;DR: It is shown that thin films of hafnium dioxide (HfO2), an insulating oxide better known as a dielectric layer for nanoscale electronic devices, can be ferromagnetic even without doping.
Abstract: It is generally accepted that magnetic order in an insulator requires the cation to have partially filled shells of d or f electrons. Here we show that thin films of hafnium dioxide (HfO2), an insulating oxide better known as a dielectric layer for nanoscale electronic devices, can be ferromagnetic even without doping. This discovery challenges our understanding of magnetism in insulators, because neither Hf4+ nor O2- are magnetic ions and the d and f shells of the Hf4+ ion are either empty or full.
1,046 citations
TL;DR: The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total Homocystinuria measurements as diagnostic or screening tests in several target populations.
Abstract: Background: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations. Methods: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years. Outcome: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.
1,001 citations
01 Jan 2004
TL;DR: This paper considers different types of concept drift, peculiarities of the problem, and gives a critical review of existing approaches to the problem.
Abstract: Alexey Tsymbal Department of Computer Science Trinity College Dublin, Ireland tsymbalo@tcd.ie April 29, 2004 Abstract In the real world concepts are often not stable but change with time. Typical examples of this are weather prediction rules and customers’ preferences. The underlying data distribution may change as well. Often these changes make the model built on old data inconsistent with the new data, and regular updating of the model is necessary. This problem, known as concept drift, complicates the task of learning a model from data and requires special approaches, different from commonly used techniques, which treat arriving instances as equally important contributors to the final concept. This paper considers different types of concept drift, peculiarities of the problem, and gives a critical review of existing approaches to the problem. 1. Definitions and peculiarities of the problem A difficult problem with learning in many real-world domains is that the concept of interest may depend on some hidden context, not given explicitly in the form of pre-dictive features. A typical example is weather prediction rules that may vary radically with the season. Another example is the patterns of customers’ buying preferences that may change with time, depending on the current day of the week, availability of alter-natives, inflation rate, etc. Often the cause of change is hidden, not known a priori, making the learning task more complicated. Changes in the hidden context can induce more or less radical changes in the target concept, which is generally known as con-cept drift (Widmer and Kubat, 1996). An effective learner should be able to track such changes and to quickly adapt to them. A difficult problem in handling concept drift is distinguishing between true concept drift and noise. Some algorithms may overreact to noise, erroneously interpreting it as concept drift, while others may be highly robust to noise, adjusting to the changes too slowly. An ideal learner should combine robustness to noise and sensitivity to concept drift (Widmer and Kubat, 1996). In many domains, hidden contexts may be expected to recur. Recurring contexts may be due to cyclic phenomena, such as seasons of the year or may be associated with irregular phenomena, such as inflation rates or market mood (Harries and Sam-mut, 1998). In such domains, in order to adapt more quickly to concept drift, concept
987 citations
TL;DR: Results are interpreted in terms of a spin-split donor impurity-band model, which can account for ferromagnetism in insulating or conducting high-k oxides with concentrations of magnetic ions that lie far below the percolation threshold.
Abstract: Room-temperature ferromagnetism is observed in (110) oriented ZnO films made from targets containing 5 at. % of Sc, Ti, V, Fe, Co, or Ni, but not Cr, Mn, or Cu ions. There are large moments, $2.6{\ensuremath{\mu}}_{B}$ and $0.5{\ensuremath{\mu}}_{B}/\mathrm{\text{dopant atom}}$ for Co- and Ti-containing oxides, respectively. There is also a moment of $0.3{\ensuremath{\mu}}_{B}/\mathrm{S}\mathrm{c}$. Magnetization is very anisotropic, with variations of up to a factor of 3 depending on the orientation of the applied field relative to the substrate. Results are interpreted in terms of a spin-split donor impurity-band model, which can account for ferromagnetism in insulating or conducting high-$k$ oxides with concentrations of magnetic ions that lie far below the percolation threshold. Magnetic moments are associated with two-electron defects in the films as well as unpaired electrons of the $3d$ ions.
979 citations
TL;DR: The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.
Abstract: Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the ≈2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive community-acquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: ≈6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC476), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.
950 citations
TL;DR: In this article, Ferromagnetic coupling of ferric ions via an electron trapped in a bridging oxygen vacancy (F center) is proposed to explain the high Curie temperature.
Abstract: Thin films grown by pulsed-laser deposition from targets of Sn0.95Fe0.05O2 are transparent ferromagnets with Curie temperature and spontaneous magnetization of 610 K and 2.2 A m2 kg−1, respectively. The 57Fe Mossbauer spectra show the iron is all high-spin Fe3+ but the films are magnetically inhomogeneous on an atomic scale, with only 23% of the iron ordering magnetically. The net ferromagnetic moment per ordered iron ion, 1.8 μB, is greater than for any simple iron oxide with superexchange interactions. Ferromagnetic coupling of ferric ions via an electron trapped in a bridging oxygen vacancy (F center) is proposed to explain the high Curie temperature.
868 citations
TL;DR: The possibility that regulatory T cells can be both beneficial to the host, through limiting the immunopathology associated with anti-pathogen immune responses, and beneficial toThe pathogen, through subversion of the protective immune responses of the host is explored.
Abstract: Homeostasis in the immune system depends on a balance between the responses that control infection and tumour growth and the reciprocal responses that prevent inflammation and autoimmune diseases. It is now recognized that regulatory T cells have a crucial role in suppressing immune responses to self-antigens and in preventing autoimmune diseases. Evidence is also emerging that regulatory T cells control immune responses to bacteria, viruses, parasites and fungi. This article explores the possibility that regulatory T cells can be both beneficial to the host, through limiting the immunopathology associated with anti-pathogen immune responses, and beneficial to the pathogen, through subversion of the protective immune responses of the host.
TL;DR: A random graph process in which vertices are added to the graph one at a time and joined to a fixed number m of earlier vertices, where each earlier vertex is chosen with probability proportional to its degree is considered.
Abstract: We consider a random graph process in which vertices are added to the graph one at a time and joined to a fixed number m of earlier vertices, where each earlier vertex is chosen with probability proportional to its degree. This process was introduced by Barabasi and Albert [3], as a simple model of the growth of real-world graphs such as the world-wide web. Computer experiments presented by Barabasi, Albert and Jeong [1,5] and heuristic arguments given by Newman, Strogatz and Watts [23] suggest that after n steps the resulting graph should have diameter approximately logn. We show that while this holds for m=1, for m≥2 the diameter is asymptotically log n/log logn.
TL;DR: The results reveal a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may play in prolonging abuse or predisposing users toward relapse.
Abstract: Using a GO-NOGO response inhibition task in which working memory (WM) demands can be varied, we demonstrate that the compromised abilities of cocaine users to exert control over strong prepotent urges are associated with reduced activity in anterior cingulate and right prefrontal cortices, two regions thought to be critical for implementing cognitive control. Furthermore, unlike drug-naive controls, and opposite to the anterior cingulate pattern, cocaine users showed an over-reliance on the left cerebellum, a compensatory pattern previously seen in alcohol addiction. The results indicate that cocaine users find it difficult to inhibit their own actions, particularly when WM demands, which have been shown previously to increase during cue-induced craving for the drug, are increased. The results reveal a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may play in prolonging abuse or predisposing users toward relapse.
TL;DR: In this paper, two types of polymer matrices, namely polyvinyl alcohol (PVA) and chlorinated polypropylene (COPP), were used to construct carbon nanotube composite films.
Abstract: Polymer–multiwalled carbon nanotube composite films were fabricated using two types of polymer matrices, namely poly(vinyl alcohol), (PVA) and chlorinated polypropylene. In the first case, the PVA was observed to form a crystalline coating around the nanotubes, maximising interfacial stress transfer. In the second case the interface was engineered by covalently attaching chlorinated polypropylene chains to the nanotubes, again resulting in large stress transfer. Increases in Young's modulus, tensile strength, and toughness of × 3.7, × 4.3, and × 1.7, respectively were observed for the PVA-based materials at less than 1 wt.-% nanotubes. Similarily for the polypropylene-based composites, increases in Young's modulus, tensile strength and toughness of × 3.1, × 3.9, and × 4.4, respectively, were observed at equivalent nanotube loading levels. In addition, a model to describe composite strength was derived. This model shows that the tensile strength increases in proportion to the thickness of the interface region. This suggests that composite strength can be optimized by maximising the thickness of the crystalline coating or the thickness of the interfacial volume partially occupied by functional groups.
01 Mar 2004
TL;DR: In this article, the problem of solving Langevin and Fokker-Planck Equations has been studied in the presence of an external potential with applications to Dielectric and Kerr Effect Relaxation in Fluids and Liquid Crystals.
Abstract: Historical Background and Introductory Concepts Methods for Solving Langevin and Fokker-Planck Equations Matrix Continued Fractions Escape Rate Theory Linear and Nonlinear Response Theory Brownian Motion of a Free Particle and a Harmonic Oscillator Rotational Brownian Motion about a Fixed Axis in a Periodic Potential Brownian Motion in a Tilted Periodic Potential: Application to the Josephson Tunnelling Junction and Ring Lasers Brownian Motion in a Double-Well Potential Isotropic and Anisotropic Rotational Brownian Motion in Space in the Presence of an External Potential with Applications to Dielectric and Kerr Effect Relaxation in Fluids and Liquid Crystals Brownian Motion of Classical Spins with Applications to Superparamagnetism Magnetic Stochastic Resonance Dynamic Hysteresis Switching Field Surfaces Inertial Langevin Equations with Applications to Orientational Relaxation in Liquids Itinerant Oscillator Model Anomalous Diffusion Continuous Time Random Walks Methods for the Solution of Fractional Fokker-Planck Equations.
TL;DR: It is shown that the membrane-bound form of ST2 negatively regulated type I interleukin 1 receptor (IL-1RI) and Toll-like receptor 4 (TLR4) but not TLR3 signaling by sequestrating the adaptors MyD88 and Mal.
Abstract: The Toll-interleukin 1 receptor (TIR) superfamily, defined by the presence of an intracellular TIR domain, initiates innate immunity through activation of the transcription factor NF-kappa B, leading to the production of proinflammatory cytokines. ST2 is a member of the TIR family that does not activate NF-kappa B and has been suggested as an important effector molecule of T helper type 2 (T(H)2) responses. We show here that the membrane-bound form of ST2 negatively regulated type I interleukin 1 receptor (IL-1RI) and Toll-like receptor 4 (TLR4) but not TLR3 signaling by sequestrating the adaptors MyD88 and Mal. In contrast to wild-type mice, ST2-deficient mice failed to develop endotoxin tolerance. Thus, these results provide a molecular explanation for the function of ST2 in T(H)2 responses, as inhibition of TLRs promotes a T(H)2 response, and also identify ST2 as a key regulator of endotoxin tolerance.
TL;DR: In this article, an analytic method of smearing link variables in lattice QCD is proposed and tested, and the differentiability of the smearing scheme with respect to the link variables permits the use of modern Monte Carlo updating methods based on molecular dynamics evolution for gauge-field actions constructed using such smeared links.
Abstract: An analytic method of smearing link variables in lattice QCD is proposed and tested. The differentiability of the smearing scheme with respect to the link variables permits the use of modern Monte Carlo updating methods based on molecular dynamics evolution for gauge-field actions constructed using such smeared links. In examining the smeared mean plaquette and the static quark-antiquark potential, no degradation in effectiveness is observed as compared to link smearing methods currently in use, although an increased sensitivity to the smearing parameter is found.
TL;DR: Data suggest that aureolysin production by S. aureus contributes to the resistance of this pathogen to the innate immune system of humans mediated by LL-37.
Abstract: Cathelicidin LL-37 is one of the few human bactericidal peptides with potent antistaphylococcal activity. In this study we examined the susceptibility of LL-37 to proteolytic degradation by two major proteinases produced by Staphylococcus aureus, a metalloproteinase (aureolysin) and a glutamylendopeptidase (V8 protease). We found that aureolysin cleaved and inactivated LL-37 in a time- and concentration-dependent manner. Analysis of the generated fragments by mass spectroscopy revealed that the initial cleavage of LL-37 by aureolysin occurred between the Arg19-Ile20, Arg23-Ile24, and Leu31-Val32 peptide bonds, instantly annihilating the antibacterial activity of LL-37. In contrast, the V8 proteinase hydrolyzed efficiently only the Glu16-Phe17 peptide bond, rendering the C-terminal fragment refractory to further degradation. This fragment (termed LL-17-37) displayed antibacterial activity against S. aureus at a molar level similar to that of the full-length LL-37 peptide, indicating that the antibacterial activity of LL-37 resides in the C-terminal region. In keeping with LL-37 degradation by aureolysin, S. aureus strains that produce significant amounts of this metalloprotease were found to be less susceptible to LL-17-37 than strains expressing no aureolysin activity. Taken together, these data suggest that aureolysin production by S. aureus contributes to the resistance of this pathogen to the innate immune system of humans mediated by LL-37.
TL;DR: In this paper, tensile tests were carried out on free-standing composite films of poly(vinyl alcohol) and six different types of carbon nanotubes for different nanotube loading levels.
Abstract: Tensile tests were carried out on free-standing composite films of poly(vinyl alcohol) and six different types of carbon nanotubes for different nanotube loading levels. Significant increases in Young's modulus by up to a factor of 2 were observed in all cases. Theories such as the rule-of-mixtures or the Halpin-Tsai-theory could not explain the relative differences between composites made from different tube types. However, it is possible to show that the reinforcement scales linearly with the total nanotube surface area in the films, indicating that low diameter multiwall nanotubes are the best tube type for reinforcement. In addition, in all cases crystalline coatings around the nanotubes were detected by calorimetry, suggesting comparible polymer−nanotube interfaces. Thus, the reinforcement appears to be critically dependent on the polymer−nanotube interfacial interaction as previously suggested.
TL;DR: Evidence is provided that the A β-mediated inhibition of LTP induction involves stimulation of the kinases JNK, Cdk5, and p38 MAPK after the activation of both the Aβ receptor(s) and mGluR5.
Abstract: The mechanisms of action of human synthetic and naturally secreted cell-derived amyloid β-peptide (Aβ)1–42 on the induction of long-term potentiation (LTP) were investigated in the medial perforant path to dentate granule cell synapses in hippocampal slices. Synthetic and cell-derived Aβ strongly inhibited high-frequency stimulation (HFS)-induced LTP at peak HFS and 1 hr after HFS. Cell-derived Aβ was much more potent than synthetic Aβ at inhibiting LTP induction, with threshold concentrations of ∼1 and 100–200 nm, respectively. The involvement of various kinases in Aβ-mediated inhibition of LTP induction was investigated by applying Aβ in the presence of inhibitors of these kinases. The c-Jun N-terminal kinase (JNK) inhibitor JNKI prevented the block of LTP induction by both synthetic and cell-derived Aβ. The block of LTP induced by synthetic Aβ was also prevented by the JNK inhibitor anthra[1,9-cd]pyrazol-6(2H)-one, the cyclin-dependent kinase 5 (Cdk5) inhibitors butyrolactone and roscovitine, and the p38 MAP kinase (MAPK) inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole but not by the p42–p44 MAP kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene. The group I–group II metabotropic glutamate receptor (mGluR) antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid and the mGluR5 antagonist methyl-6-(phenylethynyl)pyridine prevented the block of LTP induction by Aβ. However, theα7 nicotinic ACh receptor antagonist methylcaconatine did not prevent the inhibition of LTP induction by Aβ. These studies provide evidence that the Aβ-mediated inhibition of LTP induction involves stimulation of the kinases JNK, Cdk5, and p38 MAPK after the activation of both the Aβ receptor(s) and mGluR5.
TL;DR: Both the behavioural and fMRI data are consistent with the interpretation that those subjects with relatively higher intra-individual variability activate inhibitory regions to a greater extent, perhaps reflecting a greater requirement for top-down executive control in this group, a finding that may be relevant to disorders of executive/attentional control.
TL;DR: A nomogram is developed that predicts the probability that a patient will survive pancreatic cancer for 1, 2, and 3 years from the time of the initial resection, assuming that there is not death from an alternate cause.
Abstract: Background: Predictive nomograms are becoming increasingly used to define and predict outcome. They can be developed at presentation or following treatment and include variables not conventionally used in standard staging systems. Methods: We use a predictive nomogram based on prospectively collected data from 555 pancreatic resections for adenocarcinoma at a single institution. At last follow-up, 481 (87%) had died, defining a mature and comprehensive database. We used a 1-, 2-, and 3-year follow-up, as the number of patients alive beyond 3 years is sufficiently limited to provide insufficient events. Results: Based on a Cox model, we then developed a nomogram that predicts the probability that a patient will survive pancreatic cancer for 1, 2, and 3 years from the time of the initial resection, assuming that there is not death from an alternate cause. Calibration between observed and corrected is good, and variables not conventionally associated with standard staging systems improved the predictivity of the model. Conclusions: This nomogram can serve as a basis for investigating other potentially predictive variables that are proposed of prognostic importance for patients undergoing resection for adenocarcinoma of the pancreas. (Ann Surg 2004;240: 293‐298)
14 Mar 2004
TL;DR: A framework which significantly eases the development of mobile, context-aware applications by allowing developers to fuse data from disparate sensors, represent application context, and reason efficiently about context, without the need to write complex code.
Abstract: The emergence of truly ubiquitous computing, enabled by the availability of mobile, heterogenous devices that supply context information, is currently hampered by the lack of programming support for the design and development of context-aware applications. We have developed a framework which significantly eases the development of mobile, context-aware applications. The framework allows developers to fuse data from disparate sensors, represent application context, and reason efficiently about context, without the need to write complex code. An event based communication paradigm designed specifically for ad-hoc wireless environments is incorporated, which supports loose coupling between sensors, actuators and application components.
23 May 2004
TL;DR: The Theme approach is devised for viewing the relationships between behaviours in a requirements document, identifying and isolating aspects in the requirements, and modelling those aspects using a design language.
Abstract: Aspects are behaviours that are tangled and scattered across a system. In requirements documentation, aspects manifest themselves as descriptions of behaviours that are intertwined, and woven throughout. Some aspects may be obvious, as specifications of typical crosscutting behaviour. Others may be more subtle, making them hard to identify. In either case, it is difficult to analyse requirements to locate all points in the system where aspects should be applied. These issues lead to problems achieving traceability of aspects throughout the development lifecycle. To identify aspects early in the software lifecycle, and establish sufficient traceability, developers need support for aspect identification and analysis in requirements documentation. To address this, we have devised the Theme approach for viewing the relationships between behaviours in a requirements document, identifying and isolating aspects in the requirements, and modelling those aspects using a design language. This paper describes the approach, and illustrates it with a case study and analysis.
TL;DR: A new property of staphylokinase is reported, its ability to induce secretion of defensins, to complex bind them and to neutralize their bactericidal effect.
Abstract: Alpha-defensins are peptides secreted by polymorphonuclear cells and provide antimicrobial protection mediated by disruption of the integrity of bacterial cell walls. Staphylokinase is an exoprotein produced by Staphylococcus aureus, which activates host plasminogen. In this study, we analyzed the impact of interaction between alpha-defensins and staphylokinase on staphylococcal growth. We observed that staphylokinase induced extracellular release of alpha-defensins from polymorphonuclear cells. Moreover, a direct binding between alpha-defensins and staphylokinase was shown to result in a complex formation. The biological consequence of this interaction was an almost complete inhibition of the bactericidal effect of alpha-defensins. Notably, staphylokinase with blocked plasminogen binding site still retained its ability to neutralize the bactericidal effect of alpha-defensins. In contrast, a single mutation of a staphylokinase molecule at position 74, substituting lysine for alanine, resulted in a 50% reduction of its alpha-defensin-neutralizing properties. The bactericidal properties of alpha-defensins were tested in 19 S. aureus strains in vitro and in a murine model of S. aureus arthritis. Staphylococcal strains producing staphylokinase were protected against the bactericidal effect of alpha-defensins. When staphylokinase was added to staphylokinase-negative S. aureus cultures, it almost totally abrogated the effect of alpha-defensins. Finally, human neutrophil peptide 2 injected intra-articularly along with bacteria alleviated joint destruction. In this study, we report a new property of staphylokinase, its ability to induce secretion of defensins, to complex bind them and to neutralize their bactericidal effect. Staphylokinase production may therefore be responsible in vivo for defensin resistance during S. aureus infections.
TL;DR: This issue of the JCI describes the genotyping of a large collection of nonclinical, commensal S. aureus strains from healthy individuals in a Dutch population, revealing that the S.aureus population is clonal and that some strains have enhanced virulence.
Abstract: There has been some debate about the disease-invoking potential of Staphylococcus aureus strains and whether invasive disease is associated with particularly virulent genotypes, or “superbugs.” A study in this issue of the JCI describes the genotyping of a large collection of nonclinical, commensal S. aureus strains from healthy individuals in a Dutch population. Extensive study of their genetic relatedness by amplified restriction fragment typing and comparison with strains that are associated with different types of infections revealed that the S. aureus population is clonal and that some strains have enhanced virulence. This is discussed in the context of growing interest in the mechanisms of bacterial colonization, antibiotic resistance, and novel vaccines.
TL;DR: In this article, a range of multi-wall carbon nanotubes and carbon nanofibres were mixed with a polyamide-12 matrix using a twin-screw microextruder, and the resulting blends spun to produce a series of reinforced polymer fibres.
TL;DR: A review of the current imaging literature on error-related activation indicates that, despite the use of a variety of other cognitive paradigms, the network of regions identified here is consistent with these previous studies, suggesting that these regions are critical to a 'general' error- related response.
Abstract: Three previous studies using the GO/NOGO task were examined to characterize the pattern of functional activation seen during error-related processing. The large sample size (n = 44) also allowed investigation of the influence of individual differences in age, sex, self-reported absentmindedness and reaction speed on the level of activation. Errors were seen to activate a network of regions including the anterior cingulate cortex (ACC), pre-supplementary motor area (pre-SMA), bilateral insula, thalamus and right inferior parietal lobule. Split-half comparisons performed for each of the individual difference variables indicated greater ACC and pre-SMA activation for older subjects while slower responders showed greater activation in the parietal, lateral PFC, insula and ACC regions. Whereas males and females demonstrated equivalent levels of activation in both the ACC and insula, self-reported absentmindedness related to reduced activation in these regions. Our review of the current imaging literature on error-related activation indicates that, despite the use of a variety of other cognitive paradigms, the network of regions identified here is consistent with these previous studies, suggesting that these regions are critical to a 'general' error-related response. Furthermore, this response is, in part, influenced by individual differences in both demographic characteristics and behavioural performance.
TL;DR: An HIV-infected patient in San Francisco with primary syphilis was treated with azithromycin, but the lesion did not resolve, and a mutation in the 23S rRNA genes of T. pallidum was identified.
Abstract: An HIV-infected patient in San Francisco with primary syphilis was treated with azithromycin, but the lesion did not resolve. The authors of this case report confirmed resistance to azithromycin and identified a mutation in the 23S rRNA genes of T. pallidum. The mutation was also found in samples collected in Baltimore, Seattle, and Dublin.
TL;DR: In this article, the authors compared the economics of growing Miscanthus versus traditional row crops developed by the European Union (EU) for direct combustion in local area power stations and found that the crop would yield an average of 33 t of dry matter per hectare in Illinois.
Abstract: When considering renewable energy from plants, corn ethanol and reforestation have been widely promoted. Herbaceous perennials, which produce an annual crop of above ground shoots, may have some important advantages over both of these systems. Herbaceous perennials require far fewer energy and financial inputs than annual arable crops. They can be higher yielding than forestry crops and utilize existing farm equipment. Perennial energy crops can sequester carbon into soil previously under annual arable crops, providing potential additional income in carbon credits. The advantages and disadvantages of different plant types are explained to show herbaceous perennials hold special promise as bioenergy crops. C4 photosynthesis allows greater efficiencies in the con- version of sunlight energy to biomass energy, and of nitrogen and water use. However, few plants in temperate climates use this more efficient process. One exception is the rhizomatous perennial grass Miscanthus ,w hich is aC 4 plant and exceptionally cold tolerant. Miscanthus is now being grown commercially in the European Union (EU) for direct combustion in local-area power stations. It may also have longer-term potential as a feedstock for other bio-based industry. The lessons learned from trials of this crop in the EU are summarized, potential yields in Illinois predicted and a tentative comparison of the economics of growing Miscanthus versus traditional row crops developed. Overall, the results suggest that Miscanthus could yield an average of 33 t of dry matter per hectare in Illinois. At current energy prices the crop would be profitable, if grown for 4 or more years, even without subsidy.