28,215 research outputs found
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
Single- and Multi-carrier Quadrature Amplitude Modulation: Principles and Applications for Personal Communications, WATM and Broadcasting: 2nd
No full textSingle- and Multi-carrier Quadrature Amplitude Modulation Principles and Applications for Personal Communications, WLANs and Broadcasting L. Hanzo Department of Electronics and Computer Science, University of Southampton, UK W. Webb Motorola, Arlington Heights, USA formerly at Multiple Access Communications Ltd, Southampton, UK T. Keller Ubinetics, Cambridge Technology Centre, Melbourn, UK formerly at Department of Electronics and Computer Science, University of Southampton, UK Motivated by the rapid evolution of wireless communication systems, this expanded second edition provides an overview of most major single- and multi-carrier Quadrature Amplitude Modulation (QAM) techniques commencing with simple QAM schemes for the uninitiated through to complex, rapidly-evolving areas, such as arrangements for wide-band mobile channels. Targeted at the more advanced reader, the multi-carrier modulation based second half of the book presents a research-orientated outlook using a variety of novel QAM-based arrangements. * Features six new chapters dealing with the complexities of multi-carrier modulation which has found applications ranging from Wireless Local Area Networks (WLAN) to Digital Video Broadcasting (DVB) * Provides a rudimentary introduction for readers requiring a background in the field of modulation and radio wave propagation * Discusses classic QAM transmission issues relevant to Gaussian channels * Examines QAM-based transmissions over mobile radio channels * Incorporates QAM-related orthogonal techniques, considers the spectral efficiency of QAM in cellular frequency re-use structures and presents a QAM-based speech communications system design study * Introduces Orthogonal Frequency Division Multiplexing (OFDM) over both Gaussian and wideband fading channels By providing an all-encompassing self-contained treatment of single- and multi- carrier QAM based communications, a wide range of readers including senior undergraduate and postgraduate students, practising engineers and researchers alike will all find the coverage of this book attractive
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Arlequin tailleur : comédie en un acte et en vaudevilles, avec les airs notés à la fin, Représenté à Paris, sur le Théâtre du vaudeville, le lundi 29 juillet 1793.
No full textSignatures: pi A-E[sup]4 chi. Note on t.p. verso signed by the authors: L. T. Author from Cioranescu. Cioranescu A., Bibliographie de Littérature Française du dix-huitième siècle, Paris, 1969 36310
Studies on Bis(imido) molybdenum complexes containing unsaturated hydrocarbon ligands
No full textThis thesis describes the synthesis and characterisation of molybdenum bis(imido) complexes containing unsaturated hydrocarbon ligands. A principal objective of the work was to examine the effect of various imido substituents on the coordination number of the complex and the orientations adopted by olefin and acetylene ligands. Chapter One highlights areas of transition metal chemistry relevant to the thesis, with particular emphasis on the psuedo-isolobal analogy between cyclopentadienyl and imido ligands, A convenient one-pot synthesis of molybdenum bis(imido) complexes of the type Mo(NR)(NR')Cl(_2).DME (R=R'=l-adamantyl, 2-t- BUC(_6)H(_4); R=2,6-i-Pr(_2)C(_6)H(_3), R'=t-Bu) is described in Chapter Two. Mo(N-l- adamantyl)(O)Cl(_2).DME has been synthesised, and its structure determined by single crystal X-ray diffraction.- The preparation of olefin complexes Mo(NR)(NR')(C(_2)H(_4))(PMe(_3))n (R=R'=l-adamantyl, n=l; R=R'=2-t-BuC(_6)H(_4), n=2; R=2,6-i-Pr(_2)C(_6)H(_3), R'=t- Bu, n=l) is outlined in Chapter Three. Structural information derived from NMR data has allowed comparison with metallocene-like olefin adducts. Chapter Four describes the synthesis of complexes containing σ-bound phenyl ligands (Mo(NR)(NR')(σ-C(_6)H(_5))(PMe(_3)) (R=R'=l-adamantyl, 2-t-BuC(_6)H(_4); R=2,6-i-Pr(_2)C(_6)H(_3), R'=t-Bu)) as potential precursors to benzyne complexes. Chapter Five describes the preparation of diphenylacetylene complexes Mo(NR)(NR')(PhC=CPh)(PMe(_3)), structural information derived from NMR data allows comparison with previously known metallocene-like acetylene complexes. Full experimental details for Chapters Two to Five are given in Chapter Six
Aspects of supersymmetry in multiple membrane theories
No full textPhDThis thesis consists of two parts. In the rst part we investigate the worldvolume
supersymmetry algebra of multiple membrane theories. We begin with a description
of M-theory branes and their intersections from the perspective of spacetime
and worldvolume supersymmetry algebras. We then provide an overview of the
recent work on multiple M2-branes focusing on the Bagger-Lambert theory and
its relation to the Nambu-Poisson M5-brane and the ABJM theory. The worldvolume
supersymmetry algebras of these theories are explicitly calculated and the
charges interpreted in terms of spacetime intersections of M-branes.
The second part of the thesis looks at l3
p corrections to the supersymmetry
transformations of the Bagger-Lambert theory. We begin with a review of the
dNS duality transformation which allows a gauge eld to be dualised to a scalar
eld in 2+1 dimensions. Applying this duality to 02 terms of the non-abelian
D2-brane theory gives rise to the l3
p corrections of the Lorentzian Bagger-Lambert
theory. We then apply this duality transformation to the 02 corrections of the
D2-brane supersymmetry transformations. For the `abelian' Bagger-Lambert theory
we are able to uniquely determine the l3
p corrections to the supersymmetry
transformations of the scalar and fermion elds. Generalising to the `non-abelian'
Bagger-Lambert theory we are able to determine the l3
p correction to the supersymmetry
transformation of the fermion eld. Along the way make a number of
observations relating to the implementation of the dNS duality transformation at
the level of supersymmetry transformations
Clinicial and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review
No full textBackground Alzheimer’s disease is the most common cause of dementia and is characterised by an insidious onset and slow deterioration. The estimated prevalence of Alzheimer’s disease for a standard health authority (500,000 people) is about 3330. Current service involves a wide range of agencies, and drug therapy for some patients.Objectives To provide a rapid and systematic review of the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine in the symptomatic treatment of people suffering from Alzheimer’s disease.Methods A systematic review of the literature was undertaken.Data sourcesSearches were made of electronic databases, including MEDLINE, EMBASE, The Cochrane Library, Database of Abstracts of Reviews of Effectiveness, NHS Economic Evaluation Database, National Research Register, Science Citation Index, BIOSIS, EconLit, MRC Trials database, Early Warning System, Current Controlled Trials, TOXLINE, Index of Scientific and Technical Proceedings, and Getting Easier Access to Reviews. All sources were searched over the period covered by the databases up to March/July 2000. Biblioýraphies of related papers were assessed for relevant studies and experts were contacted for advice and peer review, and to identify additional published and unpublished references. Manufacturer submissions to the National Institute for Clinical Excellence (NICE) were reviewed.Study selectionStudies were included if they fulfilled the following criteria.Intervention: donepezil, rivastigmine or galantamine used to treat Alzheimer’s disease.Participants: people diagnosed with Alzheimer’s disease who meet the criteria for treatment with donepezil, rivastigmine and galantamine.Outcomes: measures assessing changes in cognition, function, behaviour and mood, quality of life (including studies assessing carer well-being and carer-input), and time to institutionalisation.Design: systematic reviews of randomised controlled trials (RCTs) and RCTs comparing donepezil, rivastigmine or galantamine with placebo or each other or non-drug comparators were included in the review of effectiveness. Economic studies of donepezil, rivastigmine or galantamine used to treat Alzheimer’s disease that included a comparator (or placebo) and both the costs and consequence (outcomes) of treatment were included in the review of cost-effectiveness.Studies in non-English language, and abstracts and conference poster presentations of systematic reviews, RCTs and economic evaluations were excluded.Two reviewers identified studies by independently screening study titles and abstracts, and then by examining the full text of selected studies to decide inclusion.Data extraction and quality assessmentData extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of RCTs was assessed using the Jadad scale and the quality of systematic reviews was assessed using criteria developed by the NHS Centre for Reviews and Dissemination. The quality of economic evaluation studies was assessed by their internal validity (i.e. the methods used) using a standard checklist, and external validity (i.e. the generalisability of the economic study to the population of interest) using a series of relevant questions.Data synthesisThe clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine were synthesised through a narrative review with full tabulation of results of all included studies. In the economic evaluation, the reviewers assessed whether adjustments could be made to existing models to reflect the current situation in England and Wales. Results Clinical effectivenessDonepezil – three systematic reviews and five RCTs (plus four studies from industry*) were found. Results suggest that donepezil is beneficial when assessed using global and cognitive outcome measures.Rivastigmine – three systematic reviews and five RCTs (plus two studies from industry*) were found. Results suggest that rivastigmine is beneficial in terms of global outcome measures.Galantamine – one systematic review and three RCTs (plus three studies from industry*) were found. Results suggest that galantamine is beneficial in terms of global, cognitive and functional scales.Summary of benefitsIt is difficult to quantify benefits from the evidence available in the literature. Statistically significant improvements in tests such as ADAS-cog (Alzheimer’s Disease Assessment Scale cognitive subscale) may not be reflected in changes in daily life.Costs/cost-effectivenessNine economic studies were found, which could not be closely compared.Donepezil – the five studies of donepezil produced a variety of cost-effectiveness estimates. While the base cases showed increased effectiveness and were cost saving in two studies, they were more costly in the other three. When sensitivity analyses are taken into consideration, estimates fluctuated more widely and there were, in some cases, conflicting results for sub-group analyses, thus casting doubt on the robustness of the estimates.Rivastigmine – of the four rivastigmine studies, the oldest has been surpassed by more recent evaluations. Cost-effectiveness ratios in two studies could not be extracted as the associated overall effectiveness was not reported and interpretation of the costs results alone is difficult due to the exclusion of drug therapy costs. The fourth study found average net costs within the first year, but a cost saving at 2 years, but it was not clear whether the data presented could be translated into incremental cost-effectiveness ratios.Galantamine – no published economic evaluations of galantamine were found.For each drug there was a further economic analysis performed by industry*.Economic implications of prescribing these drugs are uncertain. The main issue is not drug costs per se, but the impact across different sectors. Currently, this remains unclear since the financing and provision of care for patients with Alzheimer’s disease in England and Wales is complex and difficult to unravel. Any cost savings would depend mainly on release of funds from residential care.* Unpublished data, submitted as commercial in confidence Conclusions ImplicationsOn the basis of the current evidence, the implications of the use of donepezil, rivastigmine or galantamine to treat patients with Alzheimer’s disease are unclear. The main issue is whether the modest benefits seen in the outcome measures used in the trials would translate into benefits significant to patients.Future researchFuture research should include: development of quality-of-life instruments for patients and their carers; comparisons of benefits from drugs with those from other interventions; identification of those patients likely to benefit from drug treatment; development of protocols of treatment withdrawal if not beneficial; economic evaluations. Ongoing research should provide valuable evidence
Fear Conditioning in Women With Anorexia Nervosa and Healthy Controls: A Preliminary Study
No full textAnorexia nervosa is characterized by anxiety-driven behaviors, such as food avoidance and distressing persistent thoughts about weight gain and body image. The present study used a classical fear conditioning procedure to test the processes of fear acquisition and generalization, extinction, and renewal in patients with anorexia nervosa and healthy controls. An app-based fear conditioning procedure was administered remotely to 64 patients and 60 healthy controls, over two sessions. A human female scream served as the unconditioned stimulus (US) and two neutral shapes were used as either the paired conditioned stimulus (danger cue; CSþ) or the unpaired conditioned stimulus (safe cue; CS+). Patients with anorexia nervosa reported greater threat expectancy in response to the danger cue during the extinction and renewal phases and overall higher levels of negative affect throughout the task, compared with controls. Future research is warranted to replicate these findings and highlight the role that anxiety plays in explaining fear conditioning responses in patients with anorexia nervosa
Non-classical expected utility theory with application to type indeterminacy
No full textIn this paper we extend Savage's theory of decision-making under uncertainty from a classical environment into a non-classical one. We formulate the corresponding axioms and provide representation theorems for qualitative measures and expected utility. We also propose an application in simple game context in the spirit of Harsanyi.non-classical ; uncertainty ; decision-making
Ratio of n-6/n-3 in the diets of beef cattle
No full textEffects of feeding heat-treated canola (C), soybean (S) and flax (F) or mixtures on growth and slaughter characteristics, taste and fatty acid (FA) composition of beef tissue were investigated using 128 crossbred steers to determine the potential of improving the nutritional quality of beef for humans. For Trial 1 (48 steers), dietary treatments were: roasted C, extruded C, roasted S, extruded S, roasted F and extruded F. For Trial 2 (80 steers), the dietary treatments were: S:F (1:1), S:C (1:1), C:F (1:1) and S:F:C (1:1:1), and the oilseeds were processed either by roasting or extruding before mixing. Soybean meal and soybean oil were used to give equivalent lipid and protein contents to each experimental diet. The basal diet consisted of grass silage, barley grain, vitamins and minerals. Steers were fed for a minimum of 100d then slaughtered at a uniform degree of finish. Growth and slaughter characteristics of the steers were only slightly affected by dietary treatment in that the soybean-fed steers consumed more feed and had a higher average daily gain than the canola or flax-fed animals in Trial 1. There was no difference in taste panel parameters for any of the treatments. Inclusion of flax in the diet increased the total n-3 content of meat. Similar results were found for canola and C18:1n-9 although this was not the case for soybean and the n-6 FA. For the n-6 FA in the PL and neutral lipid fractions of the meat samples, levels were correlated with high dietary levels of n-6 or n-9 with low levels of n-3 while for the n-3 FA, levels were correlated with high dietary n-3 levels and low n-6 levels. Oilseed processing method did not have an effect on any fatty acid levels. It is possible to modify the FA composition of beef meat toward a healthier profile by including heat-treated oilseeds in the diet to influence the degree of lipid metabolism in the rumen.ID: S0377840111004007; M3: Article; Accession Number: S0377840111004007; Author: M.A. McNiven (a, ⁎); Author: J.L. Duynisveld (b); Author: T. Turner (a); Author: A.W. Mitchell (a); Affiliation: Department of Health Management, Atlantic Veterinary College, University of PEI, Charlottetown, PEI, Canada C1A 4P3; Affiliation: Agriculture and Agri-Food Canada, Nappan, NS, Canada B0L 1C0; Keyword: Oilseeds; Keyword: Roasted; Keyword: Extruded; Keyword: Fatty acids; Keyword: Healthy fat; Number of Pages: 11; Language: English
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