Showing papers by "Université libre de Bruxelles published in 2005"
McGill University1, Ludwig Maximilian University of Munich2, The Royal Marsden NHS Foundation Trust3, Autonomous University of Barcelona4, Geelong Hospital5, University of Marburg6, University of Edinburgh7, Pontifícia Universidade Católica do Rio Grande do Sul8, National Taiwan University9, University of Copenhagen10, Tel Aviv Sourasky Medical Center11, Russian Academy12, University of Düsseldorf13, University of Hamburg14, University of British Columbia15, University of Bern16, Hoffmann-La Roche17, Université libre de Bruxelles18, Harvard University19
TL;DR: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer.
Abstract: background Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. methods This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. results Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. conclusions One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (clinicaltrials.gov number, NCT 00045032.)
4,815 citations
TL;DR: A revised definition and classification of cerebral palsy is presented to meet the needs of clinicians, investigators, and health officials, and provide a common language for improved communication.
Abstract: Because of the availability of new knowledge about the neurobiology of developmental brain injury, information that epidemiology and modern brain imaging is providing, the availability of more precise measuring instruments of patient performance, and the increase in studies evaluating the efficacy of therapy for the consequences of injury, the need for reconsideration of the definition and classification of cerebral palsy (CP) has become evident. Pertinent material was reviewed at an international symposium participated in by selected leaders in the preclinical and clinical sciences. Suggestions were made about the content of a revised definition and classification of CP that would meet the needs of clinicians, investigators, and health officials, and provide a common language for improved communication. With leadership and direction from an Executive Committee, panels utilized this information and have generated a revised Definition and Classification of Cerebral Palsy. The Executive Committee presents this revision and welcomes substantive comments about it.
2,214 citations
TL;DR: A survey on theoretical results on ant colony optimization, which highlights some open questions with a certain interest of being solved in the near future and discusses relations between ant colonies optimization algorithms and other approximate methods for optimization.
2,093 citations
TL;DR: This review describes MGEs, their properties that are important in horizontal gene transfer, and current opportunities to advance MGE genomics.
Abstract: Horizontal genomics is a new field in prokaryotic biology that is focused on the analysis of DNA sequences in prokaryotic chromosomes that seem to have originated from other prokaryotes or eukaryotes. However, it is equally important to understand the agents that effect DNA movement: plasmids, bacteriophages and transposons. Although these agents occur in all prokaryotes, comprehensive genomics of the prokaryotic mobile gene pool or 'mobilome' lags behind other genomics initiatives owing to challenges that are distinct from cellular chromosomal analysis. Recent work shows promise of improved mobile genetic element (MGE) genomics and consequent opportunities to take advantage - and avoid the dangers - of these 'natural genetic engineers'. This review describes MGEs, their properties that are important in horizontal gene transfer, and current opportunities to advance MGE genomics.
1,488 citations
TL;DR: Cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and anNF-kappB-independent mechanism for nutrients.
Abstract: Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially "glucose hypersensitization" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.
1,419 citations
University of Washington1, University of Queensland2, Harvard University3, Katholieke Universiteit Leuven4, University of California, San Diego5, Engelhardt Institute of Molecular Biology6, Boston University7, University of California, Santa Cruz8, Moscow State University9, University of Milan10, Université libre de Bruxelles11, Rockefeller University12
TL;DR: The purpose of the current assessment is to provide some guidance to users regarding the accuracy of currently available tools in various settings, and to provide a benchmark of data sets for assessing future tools.
Abstract: The prediction of regulatory elements is a problem where computational methods offer great hope. Over the past few years, numerous tools have become available for this task. The purpose of the current assessment is twofold: to provide some guidance to users regarding the accuracy of currently available tools in various settings, and to provide a benchmark of data sets for assessing future tools.
1,324 citations
TL;DR: Chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.
Abstract: Chronic sleep loss as a consequence of voluntary bedtime restriction is an endemic condition in modern society. Although sleep exerts marked modulatory effects on glucose metabolism, and molecular mechanisms for the interaction between sleeping and feeding have been documented, the potential impact of recurrent sleep curtailment on the risk for diabetes and obesity has only recently been investigated. In laboratory studies of healthy young adults submitted to recurrent partial sleep restriction, marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity have been demonstrated. The neuroendocrine regulation of appetite was also affected as the levels of the anorexigenic hormone leptin were decreased, whereas the levels of the orexigenic factor ghrelin were increased. Importantly, these neuroendocrine abnormalities were correlated with increased hunger and appetite, which may lead to overeating and weight gain. Consistent with these laboratory findings, a growing body of epidemiological evidence supports an association between short sleep duration and the risk for obesity and diabetes. Chronic sleep loss may also be the consequence of pathological conditions such as sleep-disordered breathing. In this increasingly prevalent syndrome, a feedforward cascade of negative events generated by sleep loss, sleep fragmentation, and hypoxia are likely to exacerbate the severity of metabolic disturbances. In conclusion, chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.
1,090 citations
TL;DR: Letrozole after tamoxifen is well-tolerated and improves both disease- free and distant disease-free survival but not overall survival, except in node-positive patients.
Abstract: BACKGROUND: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. METHODS: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. RESULTS: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P
1,065 citations
TL;DR: Theoretical and phenomenological implications of R-parity violation in supersymmetric theories are discussed in the context of particle physics and cosmology in this paper, including the relation with continuous and discrete symmetries.
949 citations
University of Groningen1, National Institute of Water and Atmospheric Research2, Moss Landing Marine Laboratories3, University of California, San Diego4, University of Tokyo5, Alfred Wegener Institute for Polar and Marine Research6, University of East Anglia7, Duke University8, University of California, Santa Barbara9, Woods Hole Oceanographic Institution10, University of Western Brittany11, Leibniz Institute for Neurobiology12, Rutgers University13, Hong Kong University of Science and Technology14, University of Miami15, Université libre de Bruxelles16, Laval University17, University of British Columbia18, Central Research Institute of Electric Power Industry19, National Institute for Environmental Studies20, University of Western Australia21, Fisheries and Oceans Canada22
TL;DR: In this paper, a comparison of eight iron experiments shows that maximum Chl a, the maximum DIC removal, and the overall DIC/Fe efficiency all scale inversely with depth of the wind mixed layer (WML) defining the light environment.
Abstract: Comparison of eight iron experiments shows that maximum Chl a, the maximum DIC removal, and the overall DIC/Fe efficiency all scale inversely with depth of the wind mixed layer (WML) defining the light environment. Moreover, lateral patch dilution, sea surface irradiance, temperature, and grazing play additional roles. The Southern Ocean experiments were most influenced by very deep WMLs. In contrast, light conditions were most favorable during SEEDS and SERIES as well as during IronEx-2. The two extreme experiments, EisenEx and SEEDS, can be linked via EisenEx bottle incubations with shallower simulated WML depth. Large diatoms always benefit the most from Fe addition, where a remarkably small group of thriving diatom species is dominated by universal response of Pseudo-nitzschia spp. Significant response of these moderate (10–30 μm), medium (30–60 μm), and large (>60 μm) diatoms is consistent with growth physiology determined for single species in natural seawater. The minimum level of “dissolved” Fe (filtrate < 0.2 μm) maintained during an experiment determines the dominant diatom size class. However, this is further complicated by continuous transfer of original truly dissolved reduced Fe(II) into the colloidal pool, which may constitute some 75% of the “dissolved” pool. Depth integration of carbon inventory changes partly compensates the adverse effects of a deep WML due to its greater integration depths, decreasing the differences in responses between the eight experiments. About half of depth-integrated overall primary productivity is reflected in a decrease of DIC. The overall C/Fe efficiency of DIC uptake is DIC/Fe ∼ 5600 for all eight experiments. The increase of particulate organic carbon is about a quarter of the primary production, suggesting food web losses for the other three quarters. Replenishment of DIC by air/sea exchange tends to be a minor few percent of primary CO2 fixation but will continue well after observations have stopped. Export of carbon into deeper waters is difficult to assess and is until now firmly proven and quite modest in only two experiments.
921 citations
TL;DR: A key distribution scheme provably secure against general attacks by a postquantum eavesdropper limited only by the impossibility of superluminal signaling is described, which stems from violation of a Bell inequality.
Abstract: Standard quantum key distribution protocols are provably secure against eavesdropping attacks, if quantum theory is correct It is theoretically interesting to know if we need to assume the validity of quantum theory to prove the security of quantum key distribution, or whether its security can be based on other physical principles The question would also be of practical interest if quantum mechanics were ever to fail in some regime, because a scientifically and technologically advanced eavesdropper could perhaps use postquantum physics to extract information from quantum communications without necessarily causing the quantum state disturbances on which existing security proofs rely Here we describe a key distribution scheme provably secure against general attacks by a postquantum eavesdropper limited only by the impossibility of superluminal signaling Its security stems from violation of a Bell inequality
University of Waterloo1, Meteorological Service of Canada2, University of Paris3, Université libre de Bruxelles4, NASA Headquarters5, Belgian Institute for Space Aeronomy6, University of Toronto7, Trent University8, University of Western Ontario9, Goddard Space Flight Center10, University of Saskatchewan11, York University12, Canadian Space Agency13, Langley Research Center14, Laval University15, At Bristol16
TL;DR: The Atmospheric Chemistry Experiment (ACE) is a Canadian satellite mission for remote sensing of the Earth's atmosphere that was launched into low Earth circular orbit (altitude 650 km, inclination 74°) on 12 Aug. 2003.
Abstract: SCISAT-1, also known as the Atmospheric Chemistry Experiment (ACE), is a Canadian satellite mission for remote sensing of the Earth's atmosphere. It was launched into low Earth circular orbit (altitude 650 km, inclination 74°) on 12 Aug. 2003. The primary ACE instrument is a high spectral resolution (0.02 cm-1) Fourier Transform Spectrometer (FTS) operating from 2.2 to 13.3 μm (750-4400 cm-1). The satellite also features a dual spectrophotometer known as MAESTRO with wavelength coverage of 285-1030 nm and spectral resolution of 1-2 nm. A pair of filtered CMOS detector arrays records images of the Sun at 0.525 and 1.02 μm. Working primarily in solar occultation, the satellite provides altitude profile information (typically 10-100 km) for temperature, pressure, and the volume mixing ratios for several dozen molecules of atmospheric interest, as well as atmospheric extinction profiles over the latitudes 85°N to 85°S. This paper presents a mission overview and some of the first scientific results. Copyright 2005 by the American Geophysical Union.
Kevork N. Abazajian1, Jennifer K. Adelman-McCarthy2, Marcel A. Agüeros3, S. Allam2 +164 more•Institutions (47)
TL;DR: The Third Data Release of the Sloan Digital Sky Survey (SDSS) as mentioned in this paper contains data taken up through 2003 June, including imaging data in five bands over 5282 deg2, photometric and astrometric catalogs of the 141 million objects detected in these imaging data, and spectra of 528,640 objects selected over 4188 deg2.
Abstract: This paper describes the Third Data Release of the Sloan Digital Sky Survey (SDSS). This release, containing data taken up through 2003 June, includes imaging data in five bands over 5282 deg2, photometric and astrometric catalogs of the 141 million objects detected in these imaging data, and spectra of 528,640 objects selected over 4188 deg2. The pipelines analyzing both images and spectroscopy are unchanged from those used in our Second Data Release.
TL;DR: The origin of the pignistic transformation is justified by a linearity requirement showing it is not ad hoc but unavoidable provides one accepts expected utility theory.
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TL;DR: The authors assesses the relationship between the impact of corruption on growth and investment and the quality of governance in a sample of 63 to 71 countries between 1970 and 1998 and find that corruption has a negative impact on growth independently from its impact on investment.
Abstract: This paper assesses the relationship between the impact of corruption on growth and investment and the quality of governance in a sample of 63 to 71 countries between 1970 and 1998. Like previous studies, we find a negative effect of corruption on both growth and investment. Unlike previous studies, we find that corruption has a negative impact on growth independently from its impact on investment. These impacts are, however, different depending on the quality of governance. They tend to worsen when indicators of the quality of governance deteriorate. This supports the “sand the wheels” view on corruption and contradicts the “grease the wheels” view, which postulates that corruption may help compensate bad governance.
TL;DR: In this paper, the authors investigate the set of correlations that are constrained only by the no-signaling principle and determine the vertices of such correlations in the case that two observers each choose from two possible measurements with $d$ outcomes.
Abstract: It is well known that measurements performed on spatially separated entangled quantum systems can give rise to correlations that are nonlocal, in the sense that a Bell inequality is violated. They cannot, however, be used for superluminal signaling. It is also known that it is possible to write down sets of ``superquantum'' correlations that are more nonlocal than is allowed by quantum mechanics, yet are still nonsignaling. Viewed as an information-theoretic resource, superquantum correlations are very powerful at reducing the amount of communication needed for distributed computational tasks. An intriguing question is why quantum mechanics does not allow these more powerful correlations. We aim to shed light on the range of quantum possibilities by placing them within a wider context. With this in mind, we investigate the set of correlations that are constrained only by the no-signaling principle. These correlations form a polytope, which contains the quantum correlations as a (proper) subset. We determine the vertices of the no-signaling polytope in the case that two observers each choose from two possible measurements with $d$ outcomes. We then consider how interconversions between different sorts of correlations may be achieved. Finally, we consider some multipartite examples.
TL;DR: RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR.
Abstract: The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16–1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26–2.02) and in studies using PCR (HR 1.40; 95% CI 1.18–1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86–1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR.
TL;DR: The synthesis of published data suggests that it is possible to derive a single unique parameterisation to describe some bottom-up processes for global modelling without consideration of species and location, and most important among these are the temperature-dependence of the maximum growth rates that characterises all three blooming species.
TL;DR: The authors assesses the relationship between the impact of corruption on growth and investment and the quality of governance in a sample of 63 to 71 countries between 1970 and 1998 and find that corruption has a negative impact on growth independently from its impact on investment.
Abstract: This paper assesses the relationship between the impact of corruption on growth and investment and the quality of governance in a sample of 63 to 71 countries between 1970 and 1998. Like previous studies, we find a negative effect of corruption on both growth and investment. Unlike previous studies, we find that corruption has a negative impact on growth independently from its impact on investment. These impacts are, however, different depending on the quality of governance. They tend to worsen when indicators of the quality of governance deteriorate. This supports the “sand the wheels” view on corruption and contradicts the “grease the wheels” view, which postulates that corruption may help compensate bad governance.
TL;DR: It is emphasized that malignant gliomas are characterized by the diffuse invasion of distant brain tissue by a myriad of single migrating cells that exhibit decreased levels of apoptosis (programmed cell death type I), thus a resistance to cytotoxic insult.
Abstract: PURPOSE: The present review aims to emphasize that malignant gliomas are characterized by the diffuse invasion of distant brain tissue by a myriad of single migrating cells that exhibit decreased levels of apoptosis (programmed cell death type I), thus a resistance to cytotoxic insult. METHODS: The present review surveys the molecular mechanisms of migration in malignant gliomas and potential issues arising from treatments, in addition to relationships between glioma cell migration and resistance to apoptosis in terms of the molecular signaling pathways. RESULTS: Clinical and experimental data demonstrate that glioma cell migration is a complex combination of multiple molecular processes, including the alteration of tumor cell adhesion to a modified extracellular matrix, the secretion of proteases by the cells, and modifications to the actin cytoskeleton. Intracellular signaling pathways involved in the acquisition of resistance to apoptosis by migrating glioma cells concern PI3K, Akt, mTOR, NF-kappaB, and autophagy (programmed cell death type II). CONCLUSION: A number of signaling pathways can be constitutively activated in migrating glioma cells, thus rendering these cells resistant to cytotoxic insults. However, these pathways are not all constitutively activated at the same time in any one glioma. Particular inhibitors should therefore only be chosen if the target is present in the tumor tissue, but this is only possible if individual patients are submitted to the molecular profiling of their tumors before undergoing any treatment to combat their migratory glioma cells. Specific antimigratory compounds should be added to conventional radio- and/or chemotherapy.
TL;DR: The results suggest that the IL-1beta + IFN-gamma-induced decrease in SERCA2b expression, with subsequent depletion of ER Ca(2+) and activation of the ER stress pathway, is a potential contributory mechanism to beta-cell death.
Abstract: Cytokines and free radicals are mediators of beta-cell death in type 1 diabetes. Under in vitro conditions, interleukin-1beta (IL-1beta) + gamma-interferon (IFN-gamma) induce nitric oxide (NO) production and apoptosis in rodent and human pancreatic beta-cells. We have previously shown, by microarray analysis of primary beta-cells, that IL-1beta + IFN-gamma decrease expression of the mRNA encoding for the sarcoendoplasmic reticulum pump Ca(2+) ATPase 2b (SERCA2b) while inducing expression of the endoplasmic reticulum stress-related and proapoptotic gene CHOP (C/EBP [CCAAT/enhancer binding protein] homologous protein). In the present study we show that cytokine-induced apoptosis and necrosis in primary rat beta-cells and INS-1E cells largely depends on NO production. IL-1beta + IFN-gamma, via NO synthesis, markedly decreased SERCA2b protein expression and depleted ER Ca(2+) stores. Of note, beta-cells showed marked sensitivity to apoptosis induced by SERCA blockers, as compared with fibroblasts. Cytokine-induced ER Ca(2+) depletion was paralleled by an NO-dependent induction of CHOP protein and activation of diverse components of the ER stress response, including activation of inositol-requiring ER-to-nucleus signal kinase 1alpha (IRE1alpha) and PRK (RNA-dependent protein kinase)-like ER kinase (PERK)/activating transcription factor 4 (ATF4), but not ATF6. In contrast, the ER stress-inducing agent thapsigargin triggered these four pathways in parallel. In conclusion, our results suggest that the IL-1beta + IFN-gamma-induced decrease in SERCA2b expression, with subsequent depletion of ER Ca(2+) and activation of the ER stress pathway, is a potential contributory mechanism to beta-cell death.
TL;DR: In this paper, the radial velocity data from a large survey performed with the CORAVEL spectrovelocimeter was used to analyze the radial velocities of stars in the solar neighbourhood.
Abstract: The availability of the Hipparcos Catalogue has triggered many kinematic and dynamical studies of the solar neighbourhood. Nevertheless, those studies generally lacked the third component of the space velocities, i.e., the radial velocities. This work presents the kinematic analysis of 5952 K and 739 M giants in the solar neighbourhood which includes for the first time radial velocity data from a large survey performed with the CORAVEL spectrovelocimeter. It also uses proper motions from the Tycho-2 catalogue, which are expected to be more accurate than the Hipparcos ones. An important by-product of this study is the observed fraction of only 5.7% of spectroscopic binaries among M giants as compared to 13.7% for K giants. After excluding the binaries for which no center-of-mass velocity could be estimated, 5311 K and 719 M giants remain in the final sample. The UV -plane constructed from these data for the stars with precise parallaxes (%) reveals a rich small-scale structure, with several clumps corresponding to the Hercules stream, the Sirius moving group, and the Hyades and Pleiades superclusters. A maximum-likelihood method, based on a Bayesian approach, has been applied to the data, in order to make full use of all the available stars (not only those with precise parallaxes) and to derive the kinematic properties of these subgroups. Isochrones in the Hertzsprung-Russell diagram reveal a very wide range of ages for stars belonging to these groups. These groups are most probably related to the dynamical perturbation by transient spiral waves (as recently modelled by De Simone et al. [CITE]) rather than to cluster remnants. A possible explanation for the presence of young group/clusters in the same area of the UV -plane is that they have been put there by the spiral wave associated with their formation, while the kinematics of the older stars of our sample has also been disturbed by the same wave. The emerging picture is thus one of dynamical streams pervading the solar neighbourhood and travelling in the Galaxy with similar space velocities. The term dynamical stream is more appropriate than the traditional term supercluster since it involves stars of different ages, not born at the same place nor at the same time. The position of those streams in the UV -plane is responsible for the vertex deviation of for the whole sample. Our study suggests that the vertex deviation for younger populations could have the same dynamical origin. The underlying velocity ellipsoid, extracted by the maximum-likelihood method after removal of the streams, is not centered on the value commonly accepted for the radial antisolar motion: it is centered on km s-1 . However, the full data set (including the various streams) does yield the usual value for the radial solar motion, when properly accounting for the biases inherent to this kind of analysis (namely, km s-1 ). This discrepancy clearly raises the essential question of how to derive the solar motion in the presence of dynamical perturbations altering the kinematics of the solar neighbourhood: does there exist in the solar neighbourhood a subset of stars having no net radial motion which can be used as a reference against which to measure the solar motion?
TL;DR: Hand transplantation is feasible with a high success rate and satisfactory functional outcome, and patients developed protective sensibility, 90% of them developed tactile sensibility and 72% also a discriminative sensibility.
Abstract: The first hand transplantation was performed in Lyon, France, on 23 September 1998 by an international team of surgeons [1]. Since then, hand transplantation programmes have been launched in the United States, Austria, China, Italy, Belgium and Poland [2, 3, 4, 5, 6], and the teams felt the need to create a worldwide registry to provide a basis for cooperation and to share their experiences (Fig. 1). Since May 2002, all groups [7] performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation (IRHCTT; www.handregistry.com). Follow-up period ranged from 2 to 85 months (Table 1). A good number of composite tissue transplantations other than the hand have been performed around the world in the period 1994–2006, including the femoral diaphysis, the knee, the larynx, the uterus, the abdominal wall, a lower limb in conjoined twins, and most recently, the face in two centres.
TL;DR: Comparative analysis of the genomes of several life forms reveals that higher mammals contain a limited number of identical genes encoding newly detected selenocysteine-containing proteins, indicating relationships between the two trace elements selenium (Se) and iodine and the hormone network.
Abstract: Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine deiodinases are selenoproteins contributing to systemic or local thyroid hormone homeostasis. The Se content in endocrine tissues (thyroid, adrenals, pituitary, testes, ovary) is higher than in many other organs. Nutritional Se depletion results in retention, whereas Se repletion is followed by a rapid accumulation of Se in endocrine tissues, reproductive organs, and the brain. Selenoproteins such as thioredoxin reductases constitute the link between the Se metabolism and the regulation of transcription by redox sensitive ligand-modulated nuclear hormone receptors. Hormones and growth factors regulate the expression of selenoproteins and, conversely, Se supply modulates hormone actions. Selenoproteins are involved in bone metabolism as well as functions of the endocrine pancreas and adrenal glands. Furthermore, spermatogenesis depends on adequate Se supply, whereas Se excess may impair ovarian function. Comparative analysis of the genomes of several life forms reveals that higher mammals contain a limited number of identical genes encoding newly detected selenocysteine-containing proteins.
TL;DR: In the present review, the pathways and mechanisms involved in lipoplex- and polyplex-mediated transfection are comparatively addressed and unresolved questions are highlighted.
TL;DR: There is an urgent need for a renewed ethical and medicolegal framework for the care of locked-in patients and patients suffering from LIS should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management.
Abstract: The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism. In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from LIS should not be denied the right to die - and to die with dignity - but also, and more importantly, they should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management. In our opinion, there is an urgent need for a renewed ethical and medicolegal framework for our care of locked-in patients.
TL;DR: This work hybridizes the solution construction mechanism of ACO with beam search, which is a well-known tree search method, and calls this approach Beam-ACO.
TL;DR: It is proposed that translational control couples insulin synthesis with folding capacity to maintain ER integrity and that this signal is essential to prevent diet-induced type 2 diabetes.
Abstract: Type 2 diabetes is a disorder of hyperglycemia resulting from failure of beta cells to produce adequate insulin to accommodate an increased metabolic demand. Here we show that regulation of mRNA translation through phosphorylation of eukaryotic initiation factor 2 (eIF2α) is essential to preserve the integrity of the endoplasmic reticulum (ER) and to increase insulin production to meet the demand imposed by a high-fat diet. Accumulation of unfolded proteins in the ER activates phosphorylation of eIF2α at Ser51 and inhibits translation. To elucidate the role of this pathway in beta-cell function we studied glucose homeostasis in Eif2s1tm1Rjk mutant mice, which have an alanine substitution at Ser51. Heterozygous (Eif2s1+/tm1Rjk) mice became obese and diabetic on a high-fat diet. Profound glucose intolerance resulted from reduced insulin secretion accompanied by abnormal distension of the ER lumen, defective trafficking of proinsulin, and a reduced number of insulin granules in beta cells. We propose that translational control couples insulin synthesis with folding capacity to maintain ER integrity and that this signal is essential to prevent diet-induced type 2 diabetes.
TL;DR: Results and a brief survey of the methods used by participants of CAPRI Rounds 3–5 suggest that genuine progress in the performance of docking methods is being achieved, with CAPRI acting as the catalyst.
Abstract: The current status of docking procedures for predicting protein-protein interactions starting from their three-dimensional (3D) structure is reassessed by evaluating blind predictions, performed during 2003-2004 as part of Rounds 3-5 of the community-wide experiment on Critical Assessment of PRedicted Interactions (CAPRI). Ten newly determined structures of protein-protein complexes were used as targets for these rounds. They comprised 2 enzyme-inhibitor complexes, 2 antigen-antibody complexes, 2 complexes involved in cellular signaling, 2 homo-oligomers, and a complex between 2 components of the bacterial cellulosome. For most targets, the predictors were given the experimental structures of 1 unbound and 1 bound component, with the latter in a random orientation. For some, the structure of the free component was derived from that of a related protein, requiring the use of homology modeling. In some of the targets, significant differences in conformation were displayed between the bound and unbound components, representing a major challenge for the docking procedures. For 1 target, predictions could not go to completion. In total, 1866 predictions submitted by 30 groups were evaluated. Over one-third of these groups applied completely novel docking algorithms and scoring functions, with several of them specifically addressing the challenge of dealing with side-chain and backbone flexibility. The quality of the predicted interactions was evaluated by comparison to the experimental structures of the targets, made available for the evaluation, using the well-agreed-upon criteria used previously. Twenty-four groups, which for the first time included an automatic Web server, produced predictions ranking from acceptable to highly accurate for all targets, including those where the structures of the bound and unbound forms differed substantially. These results and a brief survey of the methods used by participants of CAPRI Rounds 3-5 suggest that genuine progress in the performance of docking methods is being achieved, with CAPRI acting as the catalyst.
TL;DR: It is shown that movements as recorded in the Cattle Tracing System data archive, and particularly those from areas where BTB is reported, consistently outperform environmental, topographic and other anthropogenic variables as the main predictor of disease occurrence.
Abstract: For 20 years, bovine tuberculosis (BTB) has been spreading in Great Britain (England, Wales and Scotland) and is now endemic in the southwest and parts of central England and in southwest Wales, and occurs sporadically elsewhere. Although its transmission pathways remain poorly understood, the disease's distribution was previously modelled statistically by using environmental variables and measures of their seasonality. Movements of infected animals have long been considered a critical factor in the spread of livestock diseases, as reflected in strict import/export regulations, the extensive movement restrictions imposed during the 2001 foot-and-mouth disease outbreak, the tracing procedures after a new case of BTB has been confirmed and the Government's recently published strategic framework for the sustainable control on BTB. Since January 2001 it has been mandatory for stock-keepers in Great Britain to notify the British Cattle Movement Service of all cattle births, movements and deaths. Here we show that movements as recorded in the Cattle Tracing System data archive, and particularly those from areas where BTB is reported, consistently outperform environmental, topographic and other anthropogenic variables as the main predictor of disease occurrence. Simulation distribution models for 2002 and 2003, incorporating all predictor categories, are presented and used to project distributions for 2004 and 2005.