Showing papers by "University of Lisbon published in 2009"
French Institute of Health and Medical Research1, University of Paris-Sud2, Institut Gustave Roussy3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, Boston Children's Hospital11, University of Gothenburg12, University of Freiburg13, University of California, San Francisco14, Buck Institute for Research on Aging15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Yale University25, Howard Hughes Medical Institute26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, Stony Brook University45, University of Göttingen46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells
2,218 citations
University of Wisconsin-Madison1, Stanford University2, University of the West Indies3, University of the Philippines4, Columbia University5, National University of Cordoba6, Michigan State University7, United Nations8, Council for Scientific and Industrial Research9, University of Lisbon10, David and Lucile Packard Foundation11, National Autonomous University of Mexico12
TL;DR: New research is needed that considers the full ensemble of processes and feedbacks, for a range of biophysical and social systems, to better understand and manage the dynamics of the relationship between humans and the ecosystems on which they rely.
Abstract: The Millennium Ecosystem Assessment (MA) introduced a new framework for analyzing social-ecological systems that has had wide influence in the policy and scientific communities. Studies after the MA are taking up new challenges in the basic science needed to assess, project, and manage flows of ecosystem services and effects on human well-being. Yet, our ability to draw general conclusions remains limited by focus on discipline-bound sectors of the full social-ecological system. At the same time, some polices and practices intended to improve ecosystem services and human well-being are based on untested assumptions and sparse information. The people who are affected and those who provide resources are increasingly asking for evidence that interventions improve ecosystem services and human well-being. New research is needed that considers the full ensemble of processes and feedbacks, for a range of biophysical and social systems, to better understand and manage the dynamics of the relationship between humans and the ecosystems on which they rely. Such research will expand the capacity to address fundamental questions about complex social-ecological systems while evaluating assumptions of policies and practices intended to advance human well-being through improved ecosystem services.
1,939 citations
TL;DR: Basic features that facility location models must capture to support decision-making involved in strategic supply chain planning are identified and applications ranging across various industries are presented.
1,770 citations
TL;DR: In this article, a life-designing model for career intervention endorses five presuppositions about people and their work lives: contextual possibilities, dynamic processes, non-linear progression, multiple perspectives, and personal patterns.
1,428 citations
TL;DR: A conserved role for reprogramming in germline companion cells, such as nurse cells in insects and vegetative nuclei in plants, is proposed to reveal intact TEs in the genome and regulate their activity in gametes.
951 citations
Columbia University1, University of Miami2, University of North Carolina at Chapel Hill3, SUNY Downstate Medical Center4, University College London5, Cambridge University Hospitals NHS Foundation Trust6, University of California, San Francisco7, University of California, Los Angeles8, University of Alabama at Birmingham9, Rio de Janeiro State University10, University of Guadalajara11, University of Düsseldorf12, New York University13, University of Barcelona14, Shanghai Jiao Tong University15, University of Lisbon16, Stellenbosch University17, Guy's and St Thomas' NHS Foundation Trust18, Oregon Health & Science University19, University of Padua20, University of Leeds21, North Shore-LIJ Health System22, Northwestern University23, Medical University of South Carolina24, University of Birmingham25, Sun Yat-sen University26, Lille University of Science and Technology27, Charité28, Rutgers University29, Federal University of São Paulo30, University of Debrecen31, Imperial College London32, Emory University33, University of Liège34, University of Pittsburgh35, University of Paris36, University of the Witwatersrand37, California State University, Long Beach38, Royal Melbourne Hospital39, University of Texas Southwestern Medical Center40, Autonomous University of Barcelona41, Pennsylvania State University42, Johns Hopkins University43, University of Szeged44, Duke University45, University of Colorado Denver46, Harvard University47, University of Cape Town48, University of Malaya49, Peking Union Medical College50
TL;DR: Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
Abstract: Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
909 citations
TL;DR: Alzheimer's disease patients display a loss of resting-state functional connectivity in lower alpha and beta bands even when a measure insensitive to volume conduction effects is used, and the modelling results suggest that highly connected neural network 'hubs' may be especially at risk in Alzheimer's disease.
Abstract: In this study we examined changes in the large-scale structure of resting-state brain networks in patients with Alzheimer's disease compared with non-demented controls, using concepts from graph theory. Magneto-encephalograms (MEG) were recorded in 18 Alzheimer's disease patients and 18 non-demented control subjects in a no-task, eyes-closed condition. For the main frequency bands, synchronization between all pairs of MEG channels was assessed using a phase lag index (PLI, a synchronization measure insensitive to volume conduction). PLI-weighted connectivity networks were calculated, and characterized by a mean clustering coefficient and path length. Alzheimer's disease patients showed a decrease of mean PLI in the lower alpha and beta band. In the lower alpha band, the clustering coefficient and path length were both decreased in Alzheimer's disease patients. Network changes in the lower alpha band were better explained by a 'Targeted Attack' model than by a 'Random Failure' model. Thus, Alzheimer's disease patients display a loss of resting-state functional connectivity in lower alpha and beta bands even when a measure insensitive to volume conduction effects is used. Moreover, the large-scale structure of lower alpha band functional networks in Alzheimer's disease is more random. The modelling results suggest that highly connected neural network 'hubs' may be especially at risk in Alzheimer's disease.
826 citations
Northwestern University1, Princeton University2, Lawrence University3, Catholic University of Leuven4, The Chinese University of Hong Kong5, University of Poitiers6, Leiden University7, Japan Women's University8, Ewha Womans University9, Cardiff University10, University of Tromsø11, University of Granada12, University of Costa Rica13, University of Lisbon14, University of Tübingen15
TL;DR: The stereotype content model (SCM) can serve as a pancultural tool for predicting group stereotypes from structural relations with other groups in society, and comparing across societies.
Abstract: The stereotype content model (SCM) proposes potentially universal principles of societal stereotypes and their relation to social structure. Here, the SCM reveals theoretically grounded, cross-cultural, cross-groups similarities and one difference across 10 non-US nations. Seven European (individualist) and three East Asian (collectivist) nations (N=1,028) support three hypothesized cross-cultural similarities: (a) perceived warmth and competence reliably differentiate societal group stereotypes; (b) many out-groups receive ambivalent stereotypes (high on one dimension; low on the other); and (c) high status groups stereotypically are competent, whereas competitive groups stereotypically lack warmth. Data uncover one consequential cross-cultural difference: (d) the more collectivist cultures do not locate reference groups (in-groups and societal prototype groups) in the most positive cluster (high-competence/high-warmth), unlike individualist cultures. This demonstrates out-group derogation without obvious reference-group favouritism. The SCM can serve as a pancultural tool for predicting group stereotypes from structural relations with other groups in society, and comparing across societies.
765 citations
TL;DR: Cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging are useful in the diagnosis of sporadic Creutzfeldt–Jakob disease.
Abstract: Several molecular subtypes of sporadic Creutzfeldt–Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt–Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt–Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Patients with sporadic Creutzfeldt–Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt–Jakob disease’ but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt–Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt–Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic resonance imaging was positive in 83% of cases. In all definite cases, the amended criteria would cover the vast majority of suspected cases, being positive in 98%. Cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging are useful in the diagnosis of sporadic Creutzfeldt–Jakob disease. We propose an amendment to the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease to include findings from magnetic resonance imaging scans.
747 citations
TL;DR: Analysis of two breast cancer patient cohorts revealed that altered modularity of the human interactome may be useful as an indicator of breast cancer prognosis.
Abstract: Changes in the biochemical wiring of oncogenic cells drives phenotypic transformations that directly affect disease outcome. Here we examine the dynamic structure of the human protein interaction network (interactome) to determine whether changes in the organization of the interactome can be used to predict patient outcome. An analysis of hub proteins identified intermodular hub proteins that are co-expressed with their interacting partners in a tissue-restricted manner and intramodular hub proteins that are co-expressed with their interacting partners in all or most tissues. Substantial differences in biochemical structure were observed between the two types of hubs. Signaling domains were found more often in intermodular hub proteins, which were also more frequently associated with oncogenesis. Analysis of two breast cancer patient cohorts revealed that altered modularity of the human interactome may be useful as an indicator of breast cancer prognosis.
742 citations
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TL;DR: In this article, the existence of rogue waves in Bose-Einstein condensates either loaded into a parabolic trap or embedded in an optical lattice was shown to be possible.
Abstract: We predict the existence of rogue waves in Bose-Einstein condensates either loaded into a parabolic trap or embedded in an optical lattice. In the latter case, rogue waves can be observed in condensates with positive scattering length. They are immensely enhanced by the lattice. Local atomic density may increase up to tens times. We provide the initial conditions necessary for the experimental observation of the phenomenon. Numerical simulations illustrate the process of creation of rogue waves.
TL;DR: The essential differences between the interpretation of the clinical importance of patient improvements and of group differences are described and the factors to consider are discussed, which include the results of responder analyses of the primary outcome measure and analyses of secondary efficacy endpoints.
Abstract: An essential component of the interpretation of results of randomized clinical trials of treatments for chronic pain involves the determination of their clinical importance or meaningfulness. This involves two distinct processes—interpreting the clinical importance of individual patient improvements and the clinical importance of group differences—which are frequently misunderstood. In this article, we first describe the essential differences between the interpretation of the clinical importance of patient improvements and of group differences. We then discuss the factors to consider when evaluating the clinical importance of group differences, which include the results of responder analyses of the primary outcome measure, the treatment effect size compared to available therapies, analyses of secondary efficacy endpoints, the safety and tolerability of treatment, the rapidity of onset and durability of the treatment benefit, convenience, cost, limitations of existing treatments, and other factors. The clinical importance of individual patient improvements can be determined by assessing what patients themselves consider meaningful improvement using well-described methods. In contrast, the clinical meaningfulness of group differences must be determined by a multi-factorial evaluation of the benefits and risks of the treatment and of other available treatments for the condition in light of the primary goals of therapy. Such determinations must be conducted on a case-by-case basis, and are ideally informed by patients and their significant others, clinicians, researchers, statisticians, and representatives of society at large.
TL;DR: The key concepts related to CNOs are described, a high level classification of collaborative networks is provided, and some application cases in the manufacturing industry are presented.
TL;DR: This work imposes that the matter threading the wormhole satisfies the energy conditions, so that it is the effective stress-energy tensor containing higher order curvature derivatives that is responsible for the null energy condition violation.
Abstract: In this work, we construct traversable wormhole geometries in the context of f (R) modified theories of gravity. We impose that the matter threading the wormhole satisfies the energy conditions, so that it is the effective stress-energy tensor containing higher order curvature derivatives that is responsible for the null energy condition violation. Thus, the higher order curvature terms, interpreted as a gravitational fluid, sustain these nonstandard wormhole geometries, fundamentally different from their counterparts in general relativity. In particular, by considering specific shape functions and several equations of state, exact solutions for f(R) are found.
TL;DR: The GJ 581 planetary system was already known to harbor three planets, including two presumably rocky planets which straddle its habitable zone as mentioned in this paper, and it has a # 5% transit probability.
Abstract: The GJ 581 planetary system was already known to harbour three planets, including two presumably rocky planets which straddle its habitable zone. We report here the detection of an additional planet ‐ GJ 581e ‐ with a minimum mass of 1.9 M" . With a period of 3.15 days, it is the innermost planet of the system and has a # 5% transit probability. We also correct our previous confusion of the orbital period of GJ 581d (the outermost planet) with a one-year alias, thanks to an extended time span and many more measurements. The revised period is 66.8 days, and locates the semi-major axis inside the habitable zone of the low mass star. The dynamical stability of the 4-planet system imposes an upper bound on the orbital plane inclination. The planets cannot be more massive than approximately 1.6 times their minimum mass.
Leiden University Medical Center1, University of Toronto2, Paris Descartes University3, Université de Montréal4, University of Groningen5, University of Crete6, University of Lisbon7, University of Southampton8, Istanbul University9, Autonomous University of Madrid10, Ghent University11, University of Giessen12, University College Cork13, University of Copenhagen14, Universidade Federal de Santa Catarina15, University of Naples Federico II16, Menzies Research Institute17
TL;DR: In the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8, 751 rheumatologists from 17 countries participated in three separate rounds of discussions and Delphi votes as mentioned in this paper.
Abstract: Objectives: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. Methods: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. Results: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. Conclusions: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
DOI•
01 Jan 2009TL;DR: Sophisticated power management features are implemented by the present invention independent from operating system control, and the operating system need not suspend processing of other threads to process sophisticated power management procedures.
Abstract: A method and apparatus for managing power consumption in a computer system wherein the method and apparatus is compliant with the proposed Advanced Configuration and Power Interface (ACPI) specification. In one embodiment, a power management processor is sandwiched between platform hardware and the ACPI register layer. The processor processes all operating power management commands and requests while remaining transparent to the user and the operating system. In so doing, routine power management functions, so classified by the operating system, are implemented by the operating system. Sophisticated power management features, on the other hand, are implemented by the present invention independent from operating system control. Accordingly, in the present invention, the operating system need not suspend processing of other threads to process sophisticated power management procedures.
TL;DR: The segmentation methods were applied to 100 dermoscopic images and evaluated with four different metrics, using the segmentation result obtained by an experienced dermatologist as the ground truth.
Abstract: In this paper, we propose and evaluate six methods for the segmentation of skin lesions in dermoscopic images. This set includes some state of the art techniques which have been successfully used in many medical imaging problems (gradient vector flow (GVF) and the level set method of Chan et al.[(C-LS)]. It also includes a set of methods developed by the authors which were tailored to this particular application (adaptive thresholding (AT), adaptive snake (AS), EM level set (EM-LS), and fuzzy-based split-and-merge algorithm (FBSM)]. The segmentation methods were applied to 100 dermoscopic images and evaluated with four different metrics, using the segmentation result obtained by an experienced dermatologist as the ground truth. The best results were obtained by the AS and EM-LS methods, which are semi-supervised methods. The best fully automatic method was FBSM, with results only slightly worse than AS and EM-LS.
TL;DR: Presently, aablaquine and tafenoquine the two most promising primaquine analogues are already in the final stages of clinical trials against Plasmodium vivax and P. falciparum, a new hope against malaria and other primquine-sensitive illnesses, such as Pneumocystis Pneumonia or the Chagas disease.
University of Sheffield1, University of Edinburgh2, University of Saskatchewan3, University of Helsinki4, University of Washington5, Colorado State University6, Environment Canada7, University of California, Los Angeles8, University of Lisbon9, United States Forest Service10, Royal Institute of Technology11, Bridgewater State University12, University of Yamanashi13, Silver Spring Networks14, University of California, Davis15, Swedish Meteorological and Hydrological Institute16, University of Reading17, National Oceanic and Atmospheric Administration18, University of Colorado Boulder19, Swiss Federal Institute for Forest, Snow and Landscape Research20, MeteoSwiss21, Ludwig Maximilian University of Munich22, University of Texas at Austin23, Japan Agency for Marine-Earth Science and Technology24, Kyoto University25, Instituto Português do Mar e da Atmosfera26, Durham University27, Met Office28, Tohoku University29
TL;DR: In this article, three snowpack models of varying complexity and purpose were evaluated across a wide range of hydrometeorological and forest canopy conditions at five Northern Hemisphere locations, for up to three months.
Abstract: Thirty-three snowpack models of varying complexity and purpose were evaluated across a wide range of hydrometeorological and forest canopy conditions at five Northern Hemisphere locations, for up t ...
TL;DR: Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance.
Abstract: Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression. To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR. Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes. Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states.
TL;DR: In this article, a set of almost linear and sub-par dextral strike-slip faults, the SWIM1 Faults, that form a narrow band of deformation over a length of 600 km coincident with a small circle centred on the pole of rotation of Africa with respect to Eurasia, was mapped using a new swath bathymetry compilation available in the area offshore SW Portugal.
TL;DR: In this paper, an improved analysis of the final data set from the QUaD experiment was presented, which significantly improved the precision of the CMB power spectrum measurements by approximately 30%.
Abstract: We present an improved analysis of the final data set from the QUaD experiment. Using an improved technique to remove ground contamination, we double the effective sky area and hence increase the precision of our cosmic microwave background (CMB) power spectrum measurements by ~30% versus that previously reported. In addition, we have improved our modeling of the instrument beams and have reduced our absolute calibration uncertainty from 5% to 3.5% in temperature. The robustness of our results is confirmed through extensive jackknife tests, and by way of the agreement that we find between our two fully independent analysis pipelines. For the standard six-parameter ΛCDM model, the addition of QUaD data marginally improves the constraints on a number of cosmological parameters over those obtained from the WMAP experiment alone. The impact of QUaD data is significantly greater for a model extended to include either a running in the scalar spectral index, or a possible tensor component, or both. Adding both the QUaD data and the results from the Arcminute Cosmology Bolometer Array Receiver experiment, the uncertainty in the spectral index running is reduced by ~25% compared to WMAP alone, while the upper limit on the tensor-to-scalar ratio is reduced from r < 0.48 to r < 0.33 (95% c.l.). This is the strongest limit on tensors to date from the CMB alone. We also use our polarization measurements to place constraints on parity-violating interactions to the surface of last scattering, constraining the energy scale of Lorentz violating interactions to <1.5 × 10–43 GeV (68% c.l.). Finally, we place a robust upper limit on the strength of the lensing B-mode signal. Assuming a single flat band power between = 200 and = 2000, we constrain the amplitude of B-modes to be <0.57 μK2 (95% c.l.).
TL;DR: In this paper, the authors used logistic regression models to predict the likelihood of ignition occurrence, using a set of potentially explanatory variables, and produced an ignition risk map for the Portuguese mainland.
Abstract: Portugal has the highest density of wildfire ignitions among southern European countries. The ability to predict the spatial patterns of ignitions constitutes an important tool for managers, helping to improve the effectiveness of fire prevention, detection and firefighting resources allocation. In this study, we analyzed 127 490 ignitions that occurred in Portugal during a 5-year period. We used logistic regression models to predict the likelihood of ignition occurrence, using a set of potentially explanatory variables, and produced an ignition risk map for the Portuguese mainland. Results show that population density, human accessibility, land cover and elevation are important determinants of spatial distribution of fire ignitions. In this paper, we demonstrate that it is possible to predict the spatial patterns of ignitions at the national level with good accuracy and using a small number of easily obtainable variables, which can be useful in decision-making for wildfire management.
TL;DR: The role of bile acids in modulating the apoptosis process is reviewed, emphasizing the anti-apoptotic effects of UDCA and TUDCA, as well as their potential use as novel and alternate therapeutic agents for the treatment of apoptosis-related diseases.
TL;DR: Characterisation of the P. falciparum silent information regulator's A and B and their involvement in mutual exclusion and silencing of the var gene repertoire highlights the pivotal but distinct role for both PfSir2 paralogues in epigenetic silencing and the control of pathogenicity of malaria infection.
Abstract: Cytoadherance of Plasmodium falciparum-infected erythrocytes in the brain, organs and peripheral microvasculature is linked to morbidity and mortality associated with severe malaria. Parasite-derived P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) molecules displayed on the erythrocyte surface are responsible for cytoadherance and undergo antigenic variation in the course of an infection. Antigenic variation of PfEMP1 is achieved by in situ switching and mutually exclusive transcription of the var gene family, a process that is controlled by epigenetic mechanisms. Here we report characterisation of the P. falciparum silent information regulator's A and B (PfSir2A and PfSir2B) and their involvement in mutual exclusion and silencing of the var gene repertoire. Analysis of P. falciparum parasites lacking either PfSir2A or PfSir2B shows that these NAD(+)-dependent histone deacetylases are required for silencing of different var gene subsets classified by their conserved promoter type. We also demonstrate that in the absence of either of these molecules mutually exclusive expression of var genes breaks down. We show that var gene silencing originates within the promoter and PfSir2 paralogues are involved in cis spreading of silenced chromatin into adjacent regions. Furthermore, parasites lacking PfSir2A but not PfSir2B have considerably longer telomeric repeats, demonstrating a role for this molecule in telomeric end protection. This work highlights the pivotal but distinct role for both PfSir2 paralogues in epigenetic silencing of P. falciparum virulence genes and the control of pathogenicity of malaria infection.
TL;DR: It is suggested that amplitude modulation of neuronal oscillations is important for cognition and that indices of amplitude dynamics of oscillations may prove useful as neuroimaging biomarkers of early-stage AD.
Abstract: Encoding and retention of information in memory are associated with a sustained increase in the amplitude of neuronal oscillations for up to several seconds. We reasoned that coordination of oscillatory activity over time might be important for memory and, therefore, that the amplitude modulation of oscillations may be abnormal in Alzheimer disease (AD). To test this hypothesis, we measured magnetoencephalography (MEG) during eyes-closed rest in 19 patients diagnosed with early-stage AD and 16 age-matched control subjects and characterized the autocorrelation structure of ongoing oscillations using detrended fluctuation analysis and an analysis of the life- and waiting-time statistics of oscillation bursts. We found that Alzheimer's patients had a strongly reduced incidence of alpha-band oscillation bursts with long life- or waiting-times (< 1 s) over temporo-parietal regions and markedly weaker autocorrelations on long time scales (1-25 seconds). Interestingly, the life- and waiting-times of theta oscillations over medial prefrontal regions were greatly increased. Whereas both temporo-parietal alpha and medial prefrontal theta oscillations are associated with retrieval and retention of information, metabolic and structural deficits in early-stage AD are observed primarily in temporo-parietal areas, suggesting that the enhanced oscillations in medial prefrontal cortex reflect a compensatory mechanism. Together, our results suggest that amplitude modulation of neuronal oscillations is important for cognition and that indices of amplitude dynamics of oscillations may prove useful as neuroimaging biomarkers of early-stage AD.
06 Nov 2009
TL;DR: It is shown that it is possible to find ironic sentences with relatively high precision by exploring certain oral or gestural clues in user comments, such as emoticons, onomatopoeic expressions for laughter, heavy punctuation marks, quotation marks and positive interjections.
Abstract: We investigate the accuracy of a set of surface patterns in identifying ironic sentences in comments submitted by users to an on-line newspaper. The initial focus is on identifying irony in sentences containing positive predicates since these sentences are more exposed to irony, making their true polarity harder to recognize. We show that it is possible to find ironic sentences with relatively high precision (from 45% to 85%) by exploring certain oral or gestural clues in user comments, such as emoticons, onomatopoeic expressions for laughter, heavy punctuation marks, quotation marks and positive interjections. We also demonstrate that clues based on deeper linguistic information are relatively inefficient in capturing irony in user-generated content, which points to the need for exploring additional types of oral clues.
TL;DR: In an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics, and a significant fraction of resistant mutations can be beneficial in certain resistant genetic backgrounds.
Abstract: The evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact—epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics. Surprisingly we find that a significant fraction of resistant mutations can be beneficial in certain resistant genetic backgrounds, that some double resistances entail no measurable cost, and that some allelic combinations are hotspots for rapid compensation. These results provide additional insight as to why multi-resistant bacteria are so prevalent and reveal an extra layer of complexity on epistatic patterns previously unrecognized, since it is hidden in genome-wide studies of genetic interactions using gene knockouts.
TL;DR: Three-dimensional particle in cell simulations show that the intensity within the guided filament is amplified beyond its initial focused value to a normalized vector potential of a0>6, thus driving a highly nonlinear plasma wave.
Abstract: The acceleration of electrons to approximately 0.8 GeV has been observed in a self-injecting laser wakefield accelerator driven at a plasma density of 5.5x10(18) cm(-3) by a 10 J, 55 fs, 800 nm laser pulse in the blowout regime. The laser pulse is found to be self-guided for 1 cm (>10zR), by measurement of a single filament containing >30% of the initial laser energy at this distance. Three-dimensional particle in cell simulations show that the intensity within the guided filament is amplified beyond its initial focused value to a normalized vector potential of a0>6, thus driving a highly nonlinear plasma wave.