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Showing papers by "Trinity College, Dublin published in 2003"


Journal ArticleDOI
12 Jun 2003-Nature
TL;DR: This work spins 100-metre-long carbon-nanotube composite fibres that are tougher than any natural or synthetic organic fibre described so far, and uses these to make fibre supercapacitors that are suitable for weaving into textiles.
Abstract: These extraordinary composite fibres can be woven into electronic textiles. The energy needed to rupture a fibre (its toughness) is five times higher for spider silk than for the same mass of steel wire, which has inspired efforts to produce spider silk commercially1,2,3. Here we spin 100-metre-long carbon-nanotube composite fibres that are tougher than any natural or synthetic organic fibre described so far, and use these to make fibre supercapacitors that are suitable for weaving into textiles.

1,409 citations


Journal ArticleDOI
Kazuto Kobayashi1, Stanislav Dusko Ehrlich, Alessandra M. Albertini2, G. Amati2, Kasper Krogh Andersen3, Maryvonne Arnaud, Kei Asai4, S. Ashikaga5, Stéphane Aymerich, Philippe Bessières, F. Boland6, S.C. Brignell7, Sierd Bron, Keigo Bunai8, J. Chapuis, L.C. Christiansen, Antoine Danchin, Michel Débarbouillé, Etienne Dervyn, E. Deuerling9, Kevin M. Devine3, Susanne Krogh Devine3, Oliver Dreesen, Jeffery Errington10, Sabine Fillinger7, Simon J. Foster6, Yasutaro Fujita11, Alessandro Galizzi2, Rozenn Gardan, Caroline Eschevins12, Tatsuya Fukushima13, Kazuko Haga, Colin R. Harwood7, Michael Hecker, D. Hosoya14, Marie-Françoise Hullo, Hiroshi Kakeshita8, Dimitri Karamata, Yasuhiro Kasahara, Fujio Kawamura5, K. Koga5, P. Koski, Ritsuko Kuwana15, Daisuke Imamura14, M. Ishimaru14, Shu Ishikawa13, I. Ishio11, D. Le Coq, Anne Masson, Catherine Mauël, Rob Meima12, Rafael P. Mellado, Anne Moir6, Shigeki Moriya, E. Nagakawa11, Hideaki Nanamiya5, S. Nakai, Per Nygaard, Mitsuo Ogura16, T. Ohanan9, Mary O'Reilly3, M. O'Rourke6, Zoltán Prágai7, H.M. Pooley, Georges Rapoport, J.P. Rawlins10, L.A. Rivas, Carlo Rivolta, A. Sadaie, Yoshito Sadaie4, Matti Sarvas, T. Sato14, Hans Henrik Saxild, E. Scanlan3, Wolfgang Schumann9, J.F.M.L. Seegers, Junichi Sekiguchi13, Agnieszka Sekowska, Simone J. Séror, M. Simon, P. Stragier, R. Studer, Hiromu Takamatsu15, Teruo Tanaka16, M. Takeuchi14, H.B. Thomaides10, Valerie Vagner, J.M. van Dijl, Kazuhito Watabe15, Anil Wipat7, Hiroki Yamamoto13, M. Yamamoto11, Y. Yamamoto11, Kunio Yamane8, Katsunori Yata, K. Yoshida11, Hisashi Yoshikawa, Ulrich Zuber, Naotake Ogasawara 
TL;DR: To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, a systematic inactivation of Bacillus subtilis genes was carried out and most genes involved in the Embden–Meyerhof–Parnas pathway are essential.
Abstract: To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among ≈4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden–Meyerhof–Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

1,375 citations


Journal ArticleDOI
TL;DR: Comparisons of the two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers, which will help to understand the evolutionary forces that mold nematode genomes.
Abstract: The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes.

954 citations


Journal ArticleDOI
TL;DR: It is concluded that the Arabidopsis lineage underwent at least two distinct episodes of duplication, one of which was a polyploidy that occurred much more recently than estimated previously and probably during the early emergence of the crucifer family.
Abstract: The Arabidopsis genome contains numerous large duplicated chromosomal segments, but the different approaches used in previous analyses led to different interpretations regarding the number and timing of ancestral large-scale duplication events. Here, using more appropriate methodology and a more recent version of the genome sequence annotation, we investigate the scale and timing of segmental duplications in Arabidopsis. We used protein sequence similarity searches to detect duplicated blocks in the genome, used the level of synonymous substitution between duplicated genes to estimate the relative ages of the blocks containing them, and analyzed the degree of overlap between adjacent duplicated blocks. We conclude that the Arabidopsis lineage underwent at least two distinct episodes of duplication. One was a polyploidy that occurred much more recently than estimated previously, before the Arabidopsis/Brassica rapa split and probably during the early emergence of the crucifer family (24-40 Mya). An older set of duplicated blocks was formed after the monocot/dicot divergence, and the relatively low level of overlap among these blocks indicates that at least some of them are remnants of a larger duplication such as a polyploidy or aneuploidy.

707 citations


Journal ArticleDOI
TL;DR: Listeners' reactions to an utterance synthesised with seven different voice qualities were elicited in terms of pairs of opposing affective attributes, suggesting that these qualities are considerably more effective in signalling milder affective states than the strong emotions.

587 citations


Journal ArticleDOI
Ricardo Segurado1, Sevilla D. Detera-Wadleigh2, Douglas F. Levinson3, Cathryn M. Lewis4, Michael Gill, John I. Nurnberger5, Nicholas John Craddock6, J. Raymond DePaulo7, Miron Baron8, Elliot S. Gershon9, Jenny Ekholm10, Sven Cichon, Gustavo Turecki, Stephan Claes11, John R. Kelsoe12, Peter R. Schofield13, Renee F. Badenhop13, Renee F. Badenhop14, Jean Morissette15, Hilary Coon16, Douglas Blackwood17, L. Alison McInnes8, Tatiana Foroud5, Howard J. Edenberg5, Theodore Reich18, John P. Rice18, Alison Goate18, Melvin G. McInnis7, Francis J. McMahon2, Judith A. Badner9, Lynn R. Goldin2, Phil Bennett6, Virginia L. Willour7, Peter P. Zandi7, Jianjun Liu8, Conrad T. Gilliam8, S H Juo8, Wade H. Berrettini3, Takeo Yoshikawa, Leena Peltonen19, Leena Peltonen10, Jouko Lönnqvist, Markus M. Nöthen, Johannes Schumacher20, Christine Windemuth20, Marcella Rietschel, Peter Propping20, Wolfgang Maier20, Martin Alda21, Paul Grof22, Guy A. Rouleau23, Jurgen Del-Favero, Christine Van Broeckhoven, Julien Mendlewicz24, Rolf Adolfsson25, M. Anne Spence26, Hermann Luebbert, L. J. Adams13, Jennifer A. Donald27, Philip B. Mitchell14, Nicholas Barden15, Eric Shink15, William Byerley26, Walter J. Muir17, Peter M. Visscher17, Stuart MacGregor17, Hugh Gurling4, Gursharan Kalsi4, Andrew McQuillin4, Michael Escamilla28, Victor I. Reus29, Pedro León30, Nelson B. Freimer19, Henrik Ewald31, Torben A Kruse32, Ole Mors31, Uppala Radhakrishna33, Jean-Louis Blouin33, Stylianos E. Antonarakis33, Nurten A. Akarsu34 
TL;DR: The present results for the very narrow model are promising but suggest that more and larger data sets are needed to support linkage, as well as suggest that linkage might be detected in certain populations or subsets of pedigrees.
Abstract: Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder-BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A "broad" model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.

585 citations


Journal ArticleDOI
TL;DR: It is found that brief exposure to a novel environment lowered the threshold for the induction of LTP, and an important role for dopamine-regulated synaptic plasticity in the storage of unpredicted information in the CA1 area is supported.
Abstract: In addition to its role in memory formation, the hippocampus may act as a novelty detector. Here we investigated whether attention to novel events can promote the associative synaptic plasticity mechanisms believed to be necessary for storing those events in memory. We therefore examined whether exposure to a novel spatial environment promoted the induction of activity-dependent persistent increases in glutamatergic transmission (long-term potentiation, LTP) at CA1 synapses in the rat hippocampus. We found that brief exposure to a novel environment lowered the threshold for the induction of LTP. This facilitatory effect was present for a short period following novelty exposure but was absent in animals that explored a familiar environment. Furthermore, the facilitation was dependent on activation of D1/D5 receptors. These findings support an important role for dopamine-regulated synaptic plasticity in the storage of unpredicted information in the CA1 area.

520 citations


Journal ArticleDOI
TL;DR: By comparing mitochondrial and nuclear DNA sequences of modern breeds with their potential wild and domestic ancestors, new insights are gained into the timing and location of domestication events that produced the farm animals of today.
Abstract: A series of recent genetic studies has revealed the remarkably complex picture of domestication in both New World and Old World livestock. By comparing mitochondrial and nuclear DNA sequences of modern breeds with their potential wild and domestic ancestors, we have gained new insights into the timing and location of domestication events that produced the farm animals of today. The real surprise has been the high number of domestication events and the diverse locations in which they took place — factors which could radically change our approach to conserving livestock biodiversity resources in the future.

520 citations


Journal ArticleDOI
TL;DR: It is probable that differential use of adaptors will help explain the distinct pathways activated by TLRs during host defence.

498 citations


Journal ArticleDOI
TL;DR: The authors showed that the level of cyclicality varies across spending categories and across OECD countries and that countries with volatile output and dispersed political power are the most likely to run procyclical Þscal policies.

493 citations


Journal ArticleDOI
06 Mar 2003-Nature
TL;DR: In this paper, the amino-terminal alpha-helix of SRA was found to interact strongly with a carboxy terminal alpha helix of the human-specific serum protein apolipoprotein L-I (apoL-I).
Abstract: Human sleeping sickness in east Africa is caused by the parasite Trypanosoma brucei rhodesiense. The basis of this pathology is the resistance of these parasites to lysis by normal human serum (NHS). Resistance to NHS is conferred by a gene that encodes a truncated form of the variant surface glycoprotein termed serum resistance associated protein (SRA). We show that SRA is a lysosomal protein, and that the amino-terminal alpha-helix of SRA is responsible for resistance to NHS. This domain interacts strongly with a carboxy-terminal alpha-helix of the human-specific serum protein apolipoprotein L-I (apoL-I). Depleting NHS of apoL-I, by incubation with SRA or anti-apoL-I, led to the complete loss of trypanolytic activity. Addition of native or recombinant apoL-I either to apoL-I-depleted NHS or to fetal calf serum induced lysis of NHS-sensitive, but not NHS-resistant, trypanosomes. Confocal microscopy demonstrated that apoL-I is taken up through the endocytic pathway into the lysosome. We propose that apoL-I is the trypanosome lytic factor of NHS, and that SRA confers resistance to lysis by interaction with apoL-I in the lysosome.

Journal ArticleDOI
TL;DR: Higher aortic systolic blood pressure and greater arterial stiffness, in part due to reduced pulse pressure amplification and increased arterial wave reflection, suggest that the adverse hemodynamic effects have hitherto been underestimated in young chronic smokers.
Abstract: The brachial artery pressure waveform is abnormal in smokers, but the effect of smoking on the aortic pressure waveform in both smokers and nonsmokers, particularly in the younger population, is unknown. We compared the acute and chronic effects of smoking on large-artery properties in 185 healthy young smokers and nonsmokers (mean+/-SD, 22+/-5 years). We matched 41 chronic smokers for age, height, weight, and gender with 116 nonsmokers. The augmentation index, a measure of arterial wave reflection in the aorta, was measured by applanation tonometry (Sphygmocor). We also compared augmentation index, aortic pulse wave velocity (Complior), and blood pressure in 28 subjects (11 chronic smokers) before and for 15 minutes after smoking 1 cigarette (nicotine content, 1.2 mg). Although brachial blood pressure was not different, the aortic systolic blood pressure (101+/-8 versus 97+/-9 mm Hg) and augmentation index (0.7+/-13 versus -5.7+/-14) were higher (P<0.01) in chronic smokers than in nonsmokers, whereas aortic-brachial pulse pressure amplification was reduced (13.7+/-8 versus 17.7+/-5 mm Hg, P<0.01). These effects were seen in both male and female subjects. Acutely in both groups, smoking significantly increased (P<0.01) both brachial and aortic blood pressure, augmentation index, and pulse wave velocity. No changes were seen after sham smoking. This study shows an acute increase in arterial stiffness after smoking 1 cigarette in chronic smokers and nonsmokers. Higher aortic systolic blood pressure and greater arterial stiffness, in part due to reduced pulse pressure amplification and increased arterial wave reflection, suggest that the adverse hemodynamic effects have hitherto been underestimated in young chronic smokers.

Journal ArticleDOI
TL;DR: In this article, the authors describe the broad trends in international financial integration for a sample of industrial countries, and seek to explain the cross-country and time-series variation in the size of international balance sheets.
Abstract: In recent decades, foreign assets and liabilities in advanced countries have grown rapidly relative to GDP, with the increase in gross cross-holdings far exceeding the size of net positions. Moreover, the portfolio equity and FDI categories have grown in importance relative to international debt stocks. In this paper, we describe the broad trends in international financial integration for a sample of industrial countries, and seek to explain the cross-country and time-series variation in the size of international balance sheets. We also examine the behavior of the rates of return on foreign assets and liabilities, relating them to 'market' returns.

Journal ArticleDOI
TL;DR: The SECURE project investigates the design of security mechanisms for pervasive computing based on trust, and addresses how entities in unfamiliar pervasive computing environments can overcome initial suspicion to provide secure collaboration.
Abstract: The SECURE project investigates the design of security mechanisms for pervasive computing based on trust. It addresses how entities in unfamiliar pervasive computing environments can overcome initial suspicion to provide secure collaboration.

Journal ArticleDOI
TL;DR: V protein A52R blocks the activation of the transcription factor nuclear factor κB (NF-κB) by multiple TLRs, including TLR3, a recently identified receptor for viral RNA, providing further evidence for an important role for this family of receptors in the antiviral response.
Abstract: Toll-like receptors (TLRs) are crucial in the innate immune response to pathogens, in that they recognize and respond to pathogen associated molecular patterns, which leads to activation of intracellular signaling pathways and altered gene expression. Vaccinia virus (VV), the poxvirus used to vaccinate against smallpox, encodes proteins that antagonize important components of host antiviral defense. Here we show that the VV protein A52R blocks the activation of the transcription factor nuclear factor κB (NF-κB) by multiple TLRs, including TLR3, a recently identified receptor for viral RNA. A52R associates with both interleukin 1 receptor–associated kinase 2 (IRAK2) and tumor necrosis factor receptor–associated factor 6 (TRAF6), two key proteins important in TLR signal transduction. Further, A52R could disrupt signaling complexes containing these proteins. A virus deletion mutant lacking the A52R gene was attenuated compared with wild-type and revertant controls in a murine intranasal model of infection. This study reveals a novel mechanism used by VV to suppress the host immunity. We demonstrate viral disabling of TLRs, providing further evidence for an important role for this family of receptors in the antiviral response.

Journal ArticleDOI
TL;DR: The current understanding of how caspases are activated during apoptosis and inflammation and the roles these proteases play in either context are discussed.
Abstract: Members of the caspase family of cysteine proteases have been firmly established to play key roles in signal transduction cascades that culminate in apoptosis (programmed cell death). Caspases are normally expressed as inactive precursor enzymes (zymogens) that become activated during apoptosis and proceed to dismantle the cell from within. To date, three major apoptosis-associated pathways to caspase activation have been elucidated. Certain caspases, such as caspase-1, also occupy important positions in signaling pathways associated with immune responses to microbial pathogens. In this situation, caspase activation is associated with the maturation of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta) and IL-18, and not apoptosis per se. Here, we discuss the current understanding of how caspases are activated during apoptosis and inflammation and the roles these proteases play in either context.

Journal ArticleDOI
TL;DR: The data show that the MAPK kinase pathway is required for both consolidation and reconsolidation of long-term recognition memory, and that this is associated with hyperphosphorylation of ERK in different subregions of the entorhinal cortex—hippocampal circuitry.
Abstract: Consolidation and reconsolidation of long-term memory have been shown to be dependent on the synthesis of new proteins, but the specific molecular mechanisms underlying these events remain to be elucidated. The mitogen-activated protein kinase (MAPK) pathway can trigger genomic responses in neurons, leading to changes in protein synthesis, and several studies have identified its pivotal role in synaptic plasticity and long-term memory formation. In this study, we analyze the involvement of this pathway in the consolidation and reconsolidation of long-term recognition memory, using an object recognition task. We show that inhibition of the MAPK pathway by intracerebroventricular injection of the MEK [MAPK/extracellular signal-regulated kinase (ERK)] inhibitor UO126 blocks consolidation of object recognition memory but does not affect short-term memory. Brain regions of the entorhinal cortex-hippocampal circuitry were analyzed for ERK activation, and it was shown that consolidation of recognition memory was associated with increased phosphorylation of ERK in the dentate gyrus and entorhinal cortex, although total expression of ERK was unchanged. We also report that inhibition of the MAPK pathway blocks reconsolidation of recognition memory, and this was shown to be dependent on reactivation of the memory trace by brief reexposure to the objects. In addition, reconsolidation of memory was associated with an increase in the phosphorylation of ERK in entorhinal cortex and CA1. In summary, our data show that the MAPK kinase pathway is required for both consolidation and reconsolidation of long-term recognition memory, and that this is associated with hyperphosphorylation of ERK in different subregions of the entorhinal cortex-hippocampal circuitry.

Journal ArticleDOI
TL;DR: Normalisation and validity aggregation strategies are proposed to improve the prediction about the number of relevant clusters and indicate that this systematic evaluation approach may significantly support genome expression analyses for knowledge discovery applications.

Journal ArticleDOI
TL;DR: It is shown that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and in activation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory.
Abstract: There has been nearly a century of interest in the idea that encoding and storage of information in the brain requires changes in the efficacy of synaptic connections between neurons that are activated during learning. Recent research into the molecular mechanisms of long-term potentiation (LTP) has brought about new knowledge that has provided valuable insights into the neural mechanisms of memory storage. The evidence indicates that rapid activation of the genetic machinery can be a key mechanism underlying the enduring modification of neural networks required for the stability of memories. In recent years, a wealth of experimental data has highlighted the importance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAPK/ERK, cAMP response element-binding protein (CREB) and the immediate early gene (IEG) zif268 are essential components of a signalling cascade required for the expression of late phase LTP and of certain forms of long-term memory. We also present experiments in which we have assessed the role of these three molecules in recognition memory. We show that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and inactivation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory. In the continuing debate about the role of LTP mechanisms in memory, these findings provide an important complement to the suggestion that synaptic changes brought about by LTP and memory consolidation and storage share, at least in part, common underlying molecular mechanisms.

Journal ArticleDOI
TL;DR: Gastrointestinal stromal tumours (GISTs), previously classified as benign or malignant smooth muscle tumours, are the most common mesenchymal tumour of the gastrointestinal tract and there has been no effective therapy for advanced, metastatic disease until the recent introduction of the KIT inhibitor imatinib.
Abstract: Background: Gastrointestinal stromal tumours (GISTs), previously classified as benign or malignant smooth muscle tumours, are the most common mesenchymal tumours of the gastrointestinal tract. GISTs express a growth factor receptor with tyrosine kinase activity, termed KIT. Mutations of KIT are common in malignant GISTs and lead to constitutional activation of tyrosine kinase function, which causes cellular proliferation and resistance to apoptosis. GISTs are notoriously unresponsive to chemotherapy and, until the recent introduction of the KIT inhibitor imatinib, there has been no effective therapy for advanced, metastatic disease. Methods: A Medline literature search was preformed to locate all articles relating to gastrointestinal tumours, GISTs, KIT and imatinib. Results and conclusions: The 5-year survival rate after complete resection of GISTs is approximately 50 per cent. The median duration of survival for patients with a metastatic GIST is approximately 20 months, and 9–12 months for patients with local recurrence. Phase II trials have investigated the effect of imatinib on irresectable or metastatic GISTs. In these trials more than 50 per cent of patients responded to imatinib within a few months and approximately 12 per cent had disease progression. Uptake of [18F]fluoro-2-deoxy-D-glucose demonstrated by positron emission tomography has been found to be reduced after starting imatinib. The potential for cure and the optimal length of treatment is currently unknown. Imatinib is the first effective systemic therapy for metastatic and locally irresectable GISTs. Large multi-institutional clinical trials to investigate the efficacy of imatinib as adjuvant or neoadjuvant therapy for GISTs are now required. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Journal ArticleDOI
TL;DR: Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR and it remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer’s disease.
Abstract: Low n-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimer's disease, which has been associated with poor dietary fish or n-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case-control study used an established biomarker of n-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determine n-3 PUFA status in patients with Alzheimer's disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76.5 (SD 6.6) years had a clinical dementia rating (CDR) of 1 (SD 0.62) and a mini mental state examination (MMSE) score of 19.5 (SD 4.8). The control subjects (thirty-six females and nine males) aged 70 (SD 6.0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28.9 (SD 1.1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0.05 and P<0.001 respectively) in all MMSE score quartiles of patients with Alzheimer's disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimer's disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer's disease.

Journal ArticleDOI
TL;DR: In this article, the authors summarize experimental measurements of nonlinear optical adsorption in a comprehensive representative series of modified phthalocyanines substituted with various central metals and peripheral functional groups.
Abstract: Phthalocyanines have remarkable chemical and thermal stability and offer tremendous architectural flexibility in their structure, facilitating the tailoring of physical, optoelectronic, and chemical parameters. In this paper, we summarize experimental measurements of nonlinear optical adsorption in a comprehensive representative series of modified phthalocyanines substituted with various central metals and peripheral functional groups. Rate equations are used to analytically solve the static-state conditions that simulate the excited-state dynamics that result from the nonlinear excited-state adsorption, and this solution is fitted to the experimental data. General molecular engineering trends relating the optical limiting performance of these compounds to their structural characteristics are also explored and discussed.

Journal ArticleDOI
TL;DR: The fact that both increased activation of task-specific areas and increased deactivation oftask-irrelevant areas mediate cognitive functions underlying good RVIP task performance suggests two independent circuits, presumably reflecting different cognitive strategies, can be recruited to perform this vigilance task.
Abstract: Sustained attention deficits occur in several neuropsychiatric disorders. However, the underlying neurobiological mechanisms are still incompletely understood. To that end, functional MRI was used to investigate the neural substrates of sustained attention (vigilance) using the rapid visual information processing (RVIP) task in 25 healthy volunteers. In order to better understand the neural networks underlying attentional abilities, brain regions where task-induced activation correlated with task performance were identified. Performance of the RVIP task activated a network of frontal, parietal, occipital, thalamic, and cerebellar regions. Deactivation during task performance was seen in the anterior and posterior cingulate, insula, and the left temporal and parahippocampal gyrus. Good task performance, as defined by better detection of target stimuli, was correlated with enhanced activation in predominantly right fronto-parietal regions and with decreased activation in predominantly left temporo-limbic and cingulate areas. Factor analysis revealed that these performance-correlated regions were grouped into two separate networks comprised of positively activated and negatively activated intercorrelated regions. Poor performers failed to significantly activate or deactivate these networks, whereas good performers either activated the positive or deactivated the negative network, or did both. The fact that both increased activation of task-specific areas and increased deactivation of task-irrelevant areas mediate cognitive functions underlying good RVIP task performance suggests two independent circuits, presumably reflecting different cognitive strategies, can be recruited to perform this vigilance task.

Journal ArticleDOI
TL;DR: In this paper, a pan-European typology and classification system was developed for shallow lakes, which can easily be extended to all lakes, and two iterations were tested in the field on tranches of 66 lakes.
Abstract: 1. The European Water Framework Directive requires the determination of ecological status in European fresh and saline waters. This is to be through the establishment of a typology of surface water bodies, the determination of reference (high status) conditions in each element (ecotype) of the typology and of lower grades of status (good, moderate, poor and bad) for each ecotype. It then requires classification of the status of the water bodies and their restoration to at least 'good status' in a specified period. 2. Though there are many methods for assessing water quality, none has the scope of that defined in the Directive. The provisions of the Directive require a wide range of variables to be measured and give only general guidance as to how systems of classification should be established. This raises issues of comparability across States and of the costs of making the determinations. 3. Using expert workshops and subsequent field testing, a practicable pan-European typology and classification system has been developed for shallow lakes, which can easily be extended to all lakes. It is parsimonious in its choice of determinands, but based on current limnological understanding and therefore as cost-effective as possible. 4. A core typology is described, which can be expanded easily in particular States to meet local conditions. The core includes 48 ecotypes across the entire European climate gradient and incorporates climate, lake area, geology of the catchment and conductivity. 5. The classification system is founded on a liberal interpretation of Annexes in the Directive and uses variables that are inexpensive to measure and ecologically relevant. The need for taxonomic expertise is minimized. 6. The scheme has been through eight iterations, two of which were tested in the field on tranches of 66 lakes. The final version, Version 8, is offered for operational testing and further refinement by statutory authorities.

Journal ArticleDOI
TL;DR: Substantial geographic coincidence between high diversity in cattle milk genes, locations of the European Neolithic cattle farming sites and present-day lactose tolerance in Europeans suggests a gene-culture coevolution between cattle and humans.
Abstract: Milk from domestic cows has been a valuable food source for over 8,000 years, especially in lactose-tolerant human societies that exploit dairy breeds. We studied geographic patterns of variation in genes encoding the six most important milk proteins in 70 native European cattle breeds. We found substantial geographic coincidence between high diversity in cattle milk genes, locations of the European Neolithic cattle farming sites (>5,000 years ago) and present-day lactose tolerance in Europeans. This suggests a gene-culture coevolution between cattle and humans.

Journal ArticleDOI
TL;DR: Investigation revealed that the Btk-specific inhibitor, LFM-A13, inhibited the activation of NFκB by LPS in THP-1 cells, implicate Btk as a Toll/interleukin-1 receptor domain-binding protein that is important for NFκBs activation by TLR4.

Journal ArticleDOI
TL;DR: A GO/NOGO task in which errors of commission were frequent and response conflict was independently varied by manipulating response speeds suggested that two action-monitoring processes are distinct and dissociable and are localised along the midline.

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TL;DR: The findings indicate that Rot is not only a repressor but a global regulator with both positive and negative effects on the expression of S. aureus genes, and that Rot and agr have opposing effects on select target genes.
Abstract: Staphylococcus aureus produces a wide array of cell surface and extracellular proteins involved in virulence. Expression of these virulence factors is tightly controlled by numerous regulatory loci, including agr, sar, sigB, sae, and arl, as well as by a number of proteins with homology to SarA. Rot (repressor of toxins), a SarA homologue, was previously identified in a library of transposon-induced mutants created in an agr-negative strain by screening for restored protease and alpha-toxin. To date, all of the SarA homologues have been shown to act as global regulators of virulence genes. Therefore, we investigated the extent of transcriptional regulation of staphylococcal genes by Rot. We compared the transcriptional profile of a rot agr double mutant to that of its agr parental strain by using custom-made Affymetrix GeneChips. Our findings indicate that Rot is not only a repressor but a global regulator with both positive and negative effects on the expression of S. aureus genes. Our data also indicate that Rot and agr have opposing effects on select target genes. These results provide further insight into the role of Rot in the regulatory cascade of S. aureus virulence gene expression.

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TL;DR: The findings show that strong genotypic host–parasite interactions may indeed be a reliable indicator that apparently benign and highly prevalent parasites are nevertheless exerting a dramatic impact on their host populations.
Abstract: Summary 1 Parasites can have dramatic effects on the ecology of their hosts. Such strong host–parasite interactions are the result of either parasites with generally high virulence, or generally benign parasites that nevertheless express context-dependent virulence. Theoretically, one indication that an apparently benign parasite nevertheless has a large impact on its host should be the existence of strong genotypic interactions between host and parasite. 2 Crithidia bombi (Trypanosomatidae) is a highly prevalent but generally benign gut parasite of the bumble-bee Bombus terrestris. The demonstration of strong genotypic interactions between C. bombi and B. terrestris, however, suggests that context-dependent virulence may have a large impact on the host population. We thus investigated the effects of C. bombi across the entire life cycle of its host, including the stressful times of hibernation and colony-founding. Owing to the high prevalence and rates of transmission of the parasite in field populations, we used a large-scale laboratory experiment. 3 Under stressful hibernation, infected queens lost more mass. Infection also significantly reduced colony-founding success, colony size, male production and overall fitness, by up to 40%. These findings show that strong genotypic host–parasite interactions may indeed be a reliable indicator that apparently benign and highly prevalent parasites are nevertheless exerting a dramatic impact on their host populations.

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TL;DR: In this paper, organic polymers, such as poly(vinyl alcohol), polyvinyl pyrrolidone, and poly(styrene), were intercalated into single-walled carbon nanotube sheets by soaking the sheets in polymer solutions.
Abstract: Organic polymers, such as poly(vinyl alcohol), poly(vinyl pyrrolidone), and poly(styrene), were intercalated into single-walled carbon nanotube sheets by soaking the sheets in polymer solutions. Even for short soak times, significant polymer intercalation into existing free volume was observed. Tensile tests on intercalated sheets showed that the Young’s modulus, strength, and toughness increased by factors of 3, 9, and 28, respectively, indicating that the intercalated polymer enhances load transmission between nanotubes.