Showing papers by "Université libre de Bruxelles published in 2011"
The Royal Marsden NHS Foundation Trust1, University of British Columbia2, University of Edinburgh3, Imperial College London4, Queen Mary University of London5, Washington University in St. Louis6, University of Alberta7, National Institutes of Health8, University of Auvergne9, Autonomous University of Barcelona10, Harvard University11, Université libre de Bruxelles12
TL;DR: Comprehensive recommendations on preanalytical and analytical assessment, and interpretation and scoring of Ki67 were formulated based on current evidence, geared toward achieving a harmonized methodology, create greater between-laboratory and between-study comparability, and allow earlier valid applications of this marker in clinical practice.
Abstract: Uncontrolled proliferation is a hallmark of cancer. In breast cancer, immunohistochemical assessment of the proportion of cells staining for the nuclear antigen Ki67 has become the most widely used method for comparing proliferation between tumor samples. Potential uses include prognosis, prediction of relative responsiveness or resistance to chemotherapy or endocrine therapy, estimation of residual risk in patients on standard therapy and as a dynamic biomarker of treatment efficacy in samples taken before, during, and after neoadjuvant therapy, particularly neoadjuvant endocrine therapy. Increasingly, Ki67 is measured in these scenarios for clinical research, including as a primary efficacy endpoint for clinical trials, and sometimes for clinical management. At present, the enormous variation in analytical practice markedly limits the value of Ki67 in each of these contexts. On March 12, 2010, an international panel of investigators with substantial expertise in the assessment of Ki67 and in the development of biomarker guidelines was convened in London by the cochairs of the Breast International Group and North American Breast Cancer Group Biomarker Working Party to consider evidence for potential applications. Comprehensive recommendations on preanalytical and analytical assessment, and interpretation and scoring of Ki67 were formulated based on current evidence. These recommendations are geared toward achieving a harmonized methodology, create greater between-laboratory and between-study comparability, and allow earlier valid applications of this marker in clinical practice.
1,556 citations
Wellcome Trust Sanger Institute1, Université de Montréal2, University of Edinburgh3, University of Kiel4, Karolinska Institutet5, Cedars-Sinai Medical Center6, University of Cambridge7, University of Pennsylvania8, Casa Sollievo della Sofferenza9, University of Pittsburgh10, Université libre de Bruxelles11, University of Otago12, Johns Hopkins University13, Ludwig Maximilian University of Munich14, Charité15, Lille University of Science and Technology16, Cincinnati Children's Hospital Medical Center17, Ghent University18, Torbay Hospital19, University of Groningen20, Mater Health Services21, University of Liège22, University of Washington23, University of Utah24, QIMR Berghofer Medical Research Institute25, University of Paris26, University of Western Australia27, Tel Aviv University28, University of Dundee29, Harvard University30, University of Manchester31, Utrecht University32, University of Florence33, King's College London34, Yale University35, Royal Hospital for Sick Children36, Katholieke Universiteit Leuven37, Guy's and St Thomas' NHS Foundation Trust38, University of Barcelona39, University of Chicago40, University of Bern41, Agency for Science, Technology and Research42, University of California, San Francisco43, University of Toronto44, University of Oslo45, Leiden University46, University of Amsterdam47, Aarhus University48, National and Kapodistrian University of Athens49, Lithuanian University of Health Sciences50, Newcastle University51, Emory University52, Örebro University53, French Institute of Health and Medical Research54, Center for Applied Genomics55
TL;DR: A meta-analysis of six ulcerative colitis genome-wide association study datasets found many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1.
Abstract: Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.
1,291 citations
TL;DR: This work introduces a novel architecture that reduces the usually required large number of elements to a single nonlinear node with delayed feedback and proves that delay-dynamical systems, even in their simplest manifestation, can perform efficient information processing.
Abstract: Novel methods for information processing are highly desired in our information-driven society. Inspired by the brain's ability to process information, the recently introduced paradigm known as 'reservoir computing' shows that complex networks can efficiently perform computation. Here we introduce a novel architecture that reduces the usually required large number of elements to a single nonlinear node with delayed feedback. Through an electronic implementation, we experimentally and numerically demonstrate excellent performance in a speech recognition benchmark. Complementary numerical studies also show excellent performance for a time series prediction benchmark. These results prove that delay-dynamical systems, even in their simplest manifestation, can perform efficient information processing. This finding paves the way to feasible and resource-efficient technological implementations of reservoir computing.
1,121 citations
TL;DR: In this paper, the coupling, guiding and polarizing of electromagnetic waves in graphene and demonstrate a graphene-based fibre polarizer that exhibits a transverse electric-pass polarization at an extinction ratio of up to ∼27 dB in the telecommunications band.
Abstract: Scientists study the coupling, guiding and polarizing of electromagnetic waves in graphene and demonstrate a graphene-based fibre polarizer that exhibits a transverse-electric-pass polarization at an extinction ratio of up to ∼27 dB in the telecommunications band.
969 citations
TL;DR: The synthesis and polymerization of a novel thieno[3,2-b]thiophene-diketopyrrolopyrrole-based monomer is reported, which has a maximum hole mobility of 1.95 cm(2) V(-1) s(-1), which is the highest mobility from a polymer-based OFET reported to date.
Abstract: We report the synthesis and polymerization of a novel thieno[3,2-b]thiophene−diketopyrrolopyrrole-based monomer. Copolymerization with thiophene afforded a polymer with a maximum hole mobility of 1.95 cm2 V−1 s−1, which is the highest mobility from a polymer-based OFET reported to date. Bulk-heterojunction solar cells comprising this polymer and PC71BM gave a power conversion efficiency of 5.4%.
861 citations
Université libre de Bruxelles1, University of Miami2, University of Alberta3, Suffolk University4, Bond University5, St. Joseph's Healthcare Hamilton6, Durham University7, Salt Lake Regional Medical Center8, University of Utah9, Oslo University Hospital10, State University of New York System11, University of California, Los Angeles12, University of Limerick13, Konyang University14, University of Nevada, Reno15, Washington State University16, University of the Pacific (United States)17
TL;DR: Myalgic encephalomyelitis: International Consensus Criteria (Review).
Abstract: 12 FatigueConsultationClinic,SaltLake RegionalMedicalCenter; 13 InternalMedicine,FamilyPractice,UniversityofUtah,SaltLakeCity,UT,USA; 14 ME ⁄CFSCenter,OsloUniversity HospitalHF,Norway; 15 DepartmentofPaediatrics,StateUniversityofNewYork,Buffalo,NY,USA; 16 Independent,Pavia,Italy; 17 Harbor-UCLA MedicalCenter,UniversityofCalifornia,LosAngeles,CA; 18 EVMedResearch,Lomita,CA,USA; 19 UniversityofLimerick,Limerick,Ireland; 20 Pain Clinic,KonyangUniversityHospital,Daejeon,Korea; 21 DonvaleSpecialistMedicalCentre,Donvale,Victoria,Australia; 22 Departmentsof Anesthesiology,NeurobiologyandAnatomy,UniversityofUtah,SaltLakeCity,UT,USA; 23 DepartmentofMedicinaNuclear,ClinicaLasCondes, Santiago,Chile; 24 WhittemorePetersonInstitute,UniversityofNevada,Reno,NV,USA; 25 MiwaNaikaClinic,Toyama,Japan; 26 A.Kirchenstein InstituteofMicrobiologyandVirology,RigaStradinsUniversity,Riga,Latvia; 27 DepartmentofBiochemistryBand 28 DepartmentofSportsSciences,UniversityofthePacific,Stockton,CAUSA
810 citations
TL;DR: In postnatal unperturbed mammary gland, both luminal and myoepithelial lineages contain long-lived unipotent stem cells that display extensive renewing capacities, as demonstrated by their ability to clonally expand during morphogenesis and adult life as well as undergo massive expansion during several cycles of pregnancy.
Abstract: The mammary epithelium is composed of several cell lineages including luminal, alveolar and myoepithelial cells. Transplantation studies have suggested that the mammary epithelium is maintained by the presence of multipotent mammary stem cells. To define the cellular hierarchy of the mammary gland during physiological conditions, we performed genetic lineage-tracing experiments and clonal analysis of the mouse mammary gland during development, adulthood and pregnancy. We found that in postnatal unperturbed mammary gland, both luminal and myoepithelial lineages contain long-lived unipotent stem cells that display extensive renewing capacities, as demonstrated by their ability to clonally expand during morphogenesis and adult life as well as undergo massive expansion during several cycles of pregnancy. The demonstration that the mammary gland contains different types of long-lived stem cells has profound implications for our understanding of mammary gland physiology and will be instrumental in unravelling the cells at the origin of breast cancers.
765 citations
University of Cincinnati1, Northwestern University2, Harvard University3, University of Florida4, Johns Hopkins University5, University of Colorado Denver6, University of North Carolina at Chapel Hill7, Université libre de Bruxelles8, University of Amsterdam9, Vertex Pharmaceuticals10, Cedars-Sinai Medical Center11
TL;DR: Among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients.
Abstract: We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 μg per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon– ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48. Results Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, −2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001). Conclusions In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon–ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.)
762 citations
TL;DR: In this article, the transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transversal momentum resolution.
Abstract: Measurements of the jet energy calibration and transverse momentum resolution in CMS are presented, performed with a data sample collected in proton-proton collisions at a centre-of-mass energy of 7TeV, corresponding to an integrated luminosity of 36pb−1. The transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transverse momentum resolution. The results are presented for three different methods to reconstruct jets: a calorimeter-based approach, the ``Jet-Plus-Track'' approach, which improves the measurement of calorimeter jets by exploiting the associated tracks, and the ``Particle Flow'' approach, which attempts to reconstruct individually each particle in the event, prior to the jet clustering, based on information from all relevant subdetectors
750 citations
TL;DR: In this article, the authors studied the effect of collision centrality on the transverse momentum of PbPb collisions at the LHC with a data sample of 6.7 inverse microbarns.
Abstract: Jet production in PbPb collisions at a nucleon-nucleon center-of-mass energy of 2.76 TeV was studied with the CMS detector at the LHC, using a data sample corresponding to an integrated luminosity of 6.7 inverse microbarns. Jets are reconstructed using the energy deposited in the CMS calorimeters and studied as a function of collision centrality. With increasing collision centrality, a striking imbalance in dijet transverse momentum is observed, consistent with jet quenching. The observed effect extends from the lower cut-off used in this study (jet transverse momentum = 120 GeV/c) up to the statistical limit of the available data sample (jet transverse momentum approximately 210 GeV/c). Correlations of charged particle tracks with jets indicate that the momentum imbalance is accompanied by a softening of the fragmentation pattern of the second most energetic, away-side jet. The dijet momentum balance is recovered when integrating low transverse momentum particles distributed over a wide angular range relative to the direction of the away-side jet.
621 citations
TL;DR: A routine-based model of AC is proposed as a first step toward the operationalization of the AC construct, which decomposes the construct into two components, internal and external AC capabilities, and identifies the configuration of metaroutines underlying these two components.
Abstract: The 20 years following the introduction of the seminal construct of absorptive capacity (AC) by Cohen and Levinthal (Cohen, W. M., D. A. Levinthal. 1989. Innovation and learning: The two faces of RD Cohen, W. M., D. A. Levinthal. 1990. Absorptive capacity: A new perspective on learning and innovation. Admin. Sci. Quart.35(1) 128--152) have seen the proliferation of a vast literature citing the AC construct in over 10,000 published papers, chapters, and books, and interpreting it or applying it in many areas of organization science research, including organization theory, strategic management, and economics. However, with very few exceptions, the specific organizational routines and processes that constitute AC capabilities remain a black box. In this paper, we propose a routine-based model of AC as a first step toward the operationalization of the AC construct. Our intent is to direct attention to the importance of balancing internal knowledge creating processes with the identification, acquisition, and assimilation of new knowledge originating in the external environment. We decompose the construct of AC into two components, internal and external AC capabilities, and identify the configuration of metaroutines underlying these two components. These higher-level routines are expressed within organizations by configurations of empirically observable practiced routines that are idiosyncratic and firm specific. Therefore, we conceptualize metaroutines as the foundations of practiced routines. The ability of organizations to discover and implement complementarities between AC routines may explain why some firms are successful early adopters and most firms are imitators. Success as an early adopter of a new management practice or an innovation is expected to depend on the extent to which an organization evolves, adapts, and implements the configuration of its internal and external absorptive capacity routines.
National and Kapodistrian University of Athens1, Harvard University2, Université libre de Bruxelles3, Hoffmann-La Roche4, European Institute of Oncology5, The Royal Marsden NHS Foundation Trust6, Western General Hospital7, University of São Paulo8, Fudan University9, University of Toronto10, Geelong Hospital11
TL;DR: Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up and a substantial selective crossover of patients in the observation group to trastzumab was associated with improved outcomes for this cohort.
Abstract: Summary Background Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial. Methods The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48·4 months (IQR 42·0–56·5) and assess the effect of the extensive crossover to trastuzumab. Our analysis was by intention-to-treat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11. Findings The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78·6%) compared with the observation group (4-year disease-free survival 72·2%; hazard ratio [HR] 0·76; 95% CI 0·66–0·87; p vs 87·7%, respectively; HR 0·85; 95% CI 0·70–1·04; p=0·11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22·8 months (range 4·5–52·7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group (adjusted HR 0·68; 95% CI 0·51–0·90; p=0·0077). Higher incidences of grade 3–4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhoea. Interpretation Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort. Funding F Hoffmann-La Roche, Michelangelo Foundation.
TL;DR: Infinium Methylation 450K is a powerful technique in terms of reagent costs, time of labor, sample throughput and coverage, and holds great promise for the better understanding of the epigenetic component in health and disease.
Abstract: Aims: Studies of DNA methylomes hold enormous promise for biomedicine but are hampered by the technological challenges of analyzing many samples cost-effectively. Recently, a major extension of the...
TL;DR: The value of plant reintroductions as a conservation tool could be improved by an increased focus on species biology and using a higher number of transplants (preferring seedlings rather than seeds), and a consistent long-term monitoring after reintroduction.
TL;DR: Surprisingly, it was found that gene expression signatures—unrelated to cancer—of the effect of postprandial laughter, of mice social defeat and of skin fibroblast localization were all significantly associated with breast cancer outcome.
Abstract: Bridging the gap between animal or in vitro models and human disease is essential in medical research. Researchers often suggest that a biological mechanism is relevant to human cancer from the statistical association of a gene expression marker (a signature) of this mechanism, that was discovered in an experimental system, with disease outcome in humans. We examined this argument for breast cancer. Surprisingly, we found that gene expression signatures-unrelated to cancer-of the effect of postprandial laughter, of mice social defeat and of skin fibroblast localization were all significantly associated with breast cancer outcome. We next compared 47 published breast cancer outcome signatures to signatures made of random genes. Twenty-eight of them (60%) were not significantly better outcome predictors than random signatures of identical size and 11 (23%) were worst predictors than the median random signature. More than 90% of random signatures >100 genes were significant outcome predictors. We next derived a metagene, called meta-PCNA, by selecting the 1% genes most positively correlated with proliferation marker PCNA in a compendium of normal tissues expression. Adjusting breast cancer expression data for meta-PCNA abrogated almost entirely the outcome association of published and random signatures. We also found that, in the absence of adjustment, the hazard ratio of outcome association of a signature strongly correlated with meta-PCNA (R(2) = 0.9). This relation also applied to single-gene expression markers. Moreover, >50% of the breast cancer transcriptome was correlated with meta-PCNA. A corollary was that purging cell cycle genes out of a signature failed to rule out the confounding effect of proliferation. Hence, it is questionable to suggest that a mechanism is relevant to human breast cancer from the finding that a gene expression marker for this mechanism predicts human breast cancer outcome, because most markers do. The methods we present help to overcome this problem.
TL;DR: The HERMES high-resolution spectrograph project as discussed by the authors is based on the white-pupil beam folding for high resolution spectroscopy with a spectral resolution of 85'000 (63'000) for the low-resolution fiber.
Abstract: The HERMES high-resolution spectrograph project aims at exploiting the specific potential of small but flexible telescopes in observational astrophysics. The optimised optical design of the spectrograph is based on the well-proven concept of white-pupil beam folding for high-resolution spectroscopy. In this contribution we present the complete project, including the spectrograph design and procurement details, the telescope adaptor and calibration unit, the detector system, as well as the optimised data-reduction pipeline. We present a detailed performance analysis to show that the spectrograph performs as specified both in optical quality and in total efficiency. With a spectral resolution of 85 000 (63 000 for the low-resolution fibre), a spectral coverage from 377 to 900 nm in a single exposure and a peak efficiency of 28%, HERMES proves to be an ideal instrument for building up time series of high-quality data of variable (stellar) phenomena.
TL;DR: In this paper, the authors show consistency of a two-step estimation of the factors in a dynamic approximate factor model when the panel of time series is large (n large), in the first step, the parameters of the model are estimated from an OLS on principal components.
TL;DR: In this paper, the authors make use of relativistic hydrodynamical simulations of binary neutron star mergers and define consistently the conditions that determine the nucleosynthesis, i.e., neutron enrichment, entropy, early density evolution and thus expansion timescale, and ejecta mass.
Abstract: Although the rapid neutron-capture process, or r-process, is fundamentally important for explaining the origin of approximately half of the stable nuclei with A > 60, the astrophysical site of this process has not been identified yet. Here we study r-process nucleosynthesis in material that is dynamically ejected by tidal and pressure forces during the merging of binary neutron stars (NSs) and within milliseconds afterward. For the first time we make use of relativistic hydrodynamical simulations of such events, defining consistently the conditions that determine the nucleosynthesis, i.e., neutron enrichment, entropy, early density evolution and thus expansion timescale, and ejecta mass. We find that 10–3-10–2 M ☉ are ejected, which is enough for mergers to be the main source of heavy (A 140) galactic r-nuclei for merger rates of some 10–5 yr–1. While asymmetric mergers eject 2-3 times more mass than symmetric ones, the exact amount depends weakly on whether the NSs have radii of ~15 km for a "stiff" nuclear equation of state (EOS) or ~12 km for a "soft" EOS. r-process nucleosynthesis during the decompression becomes largely insensitive to the detailed conditions because of efficient fission recycling, producing a composition that closely follows the solar r-abundance distribution for nuclei with mass numbers A > 140. Estimating the light curve powered by the radioactive decay heating of r-process nuclei with an approximative model, we expect high emission in the B-V-R bands for 1-2 days with potentially observable longer duration in the case of asymmetric mergers because of the larger ejecta mass.
TL;DR: In this article, the authors make use of relativistic hydrodynamical simulations of binary neutron star mergers and define consistently the conditions that determine the nucleosynthesis, i.e., neutron enrichment, entropy, early density evolution and thus expansion timescale, and ejecta mass.
Abstract: Although the rapid neutron-capture process, or r-process, is fundamentally important for explaining the origin of approximately half of the stable nuclei with A > 60, the astrophysical site of this process has not been identified yet. Here we study r-process nucleosynthesis in material that is dynamically ejected by tidal and pressure forces during the merging of binary neutron stars (NSs) and within milliseconds afterwards. For the first time we make use of relativistic hydrodynamical simulations of such events, defining consistently the conditions that determine the nucleosynthesis, i.e., neutron enrichment, entropy, early density evolution and thus expansion timescale, and ejecta mass. We find that 10^{-3}-10^{-2} solar masses are ejected, which is enough for mergers to be the main source of heavy (A > 140) galactic r-nuclei for merger rates of some 10^{-5} per year. While asymmetric mergers eject 2-3 times more mass than symmetric ones, the exact amount depends weakly on whether the NSs have radii of ~15 km for a "stiff" nuclear equation of state (EOS) or ~12 km for a "soft" EOS. R-process nucleosynthesis during the decompression becomes largely insensitive to the detailed conditions because of efficient fission recycling, producing a composition that closely follows the solar r-abundance distribution for nuclei with mass numbers A > 140. Estimating the light curve powered by the radioactive decay heating of r-process nuclei with an approximative model, we expect high emission in the B-V-R bands for 1-2 days with potentially observable longer duration in the case of asymmetric mergers because of the larger ejecta mass.
TL;DR: A dual role is identified for tumour-cell-derived V EGF in promoting cancer stemness: by stimulating angiogenesis in a paracrine manner, VEGF creates a perivascular niche for CSCs, and by directly affecting CSC’s through Nrp1 in an autocrine loop, VegF stimulatescancer stemness and renewal.
Abstract: Angiogenesis is critical during tumour initiation and malignant progression. Different strategies aimed at blocking vascular endothelial growth factor (VEGF) and its receptors have been developed to inhibit angiogenesis in cancer patients. It has become increasingly clear that in addition to its effect on angiogenesis, other mechanisms including a direct effect of VEGF on tumour cells may account for the efficiency of VEGF-blockade therapies. Cancer stem cells (CSCs) have been described in various cancers including squamous tumours of the skin. Here we use a mouse model of skin tumours to investigate the impact of the vascular niche and VEGF signalling on controlling the stemness (the ability to self renew and differentiate) of squamous skin tumours during the early stages of tumour progression. We show that CSCs of skin papillomas are localized in a perivascular niche, in the immediate vicinity of endothelial cells. Furthermore, blocking VEGFR2 caused tumour regression not only by decreasing the microvascular density, but also by reducing CSC pool size and impairing CSC renewal properties. Conditional deletion of Vegfa in tumour epithelial cells caused tumours to regress, whereas VEGF overexpression by tumour epithelial cells accelerated tumour growth. In addition to its well-known effect on angiogenesis, VEGF affected skin tumour growth by promoting cancer stemness and symmetric CSC division, leading to CSC expansion. Moreover, deletion of neuropilin-1 (Nrp1), a VEGF co-receptor expressed in cutaneous CSCs, blocked VEGF's ability to promote cancer stemness and renewal. Our results identify a dual role for tumour-cell-derived VEGF in promoting cancer stemness: by stimulating angiogenesis in a paracrine manner, VEGF creates a perivascular niche for CSCs, and by directly affecting CSCs through Nrp1 in an autocrine loop, VEGF stimulates cancer stemness and renewal. Finally, deletion of Nrp1 in normal epidermis prevents skin tumour initiation. These results may have important implications for the prevention and treatment of skin cancers.
TL;DR: PoPMuSiC-2.1 is a web server that predicts the thermodynamic stability changes caused by single site mutations in proteins, using a linear combination of statistical potentials whose coefficients depend on the solvent accessibility of the mutated residue.
Abstract: The rational design of modified proteins with controlled stability is of extreme importance in a whole range of applications, notably in the biotechnological and environmental areas, where proteins are used for their catalytic or other functional activities. Future breakthroughs in medical research may also be expected from an improved understanding of the effect of naturally occurring disease-causing mutations on the molecular level. PoPMuSiC-2.1 is a web server that predicts the thermodynamic stability changes caused by single site mutations in proteins, using a linear combination of statistical potentials whose coefficients depend on the solvent accessibility of the mutated residue. PoPMuSiC presents good prediction performances (correlation coefficient of 0.8 between predicted and measured stability changes, in cross validation, after exclusion of 10% outliers). It is moreover very fast, allowing the prediction of the stability changes resulting from all possible mutations in a medium size protein in less than a minute. This unique functionality is user-friendly implemented in PoPMuSiC and is particularly easy to exploit. Another new functionality of our server concerns the estimation of the optimality of each amino acid in the sequence, with respect to the stability of the structure. It may be used to detect structural weaknesses, i.e. clusters of non-optimal residues, which represent particularly interesting sites for introducing targeted mutations. This sequence optimality data is also expected to have significant implications in the prediction and the analysis of particular structural or functional protein regions. To illustrate the interest of this new functionality, we apply it to a dataset of known catalytic sites, and show that a much larger than average concentration of structural weaknesses is detected, quantifying how these sites have been optimized for function rather than stability. The freely available PoPMuSiC-2.1 web server is highly useful for identifying very rapidly a list of possibly relevant mutations with the desired stability properties, on which subsequent experimental studies can be focused. It can also be used to detect sequence regions corresponding to structural weaknesses, which could be functionally important or structurally delicate regions, with obvious applications in rational protein design.
TL;DR: In this article, the authors present a review of work carried out by the eutrophication task group, and report their main findings to the scientific community, focusing on integrated approaches that account for physico-chemical and biological components.
Abstract: In 2009, following approval of the European Marine Strategy Framework Directive (MSFD, 2008/56/EC), the European Commission (EC) created task groups to develop guidance for eleven quality descriptors that form the basis for evaluating ecosystem function. The objective was to provide European countries with practical guidelines for implementing the MSFD, and to produce a Commission Decision that encapsulated key points of the work in a legal framework. This paper presents a review of work carried out by the eutrophication task group, and reports our main findings to the scientific community. On the basis of an operational, management-oriented definition, we discuss the main methodologies that could be used for coastal and marine eutrophication assessment. Emphasis is placed on integrated approaches that account for physico–chemical and biological components, and combine both pelagic and benthic symptoms of eutrophication, in keeping with the holistic nature of the MSFD. We highlight general features that any marine eutrophication model should possess, rather than making specific recommendations. European seas range from highly eutrophic systems such as the Baltic to nutrient-poor environments such as the Aegean Sea. From a physical perspective, marine waters range from high energy environments of the north east Atlantic to the permanent vertical stratification of the Black Sea. This review aimed to encapsulate that variability, recognizing that meaningful guidance should be flexible enough to accommodate the widely differing characteristics of European seas, and that this information is potentially relevant in marine ecosystems worldwide. Given the spatial extent of the MSFD, innovative approaches are required to allow meaningful monitoring and assessment. Consequently, substantial logistic and financial challenges will drive research in areas such as remote sensing of harmful algal blooms, in situ sensor development, and mathematical models. Our review takes into account related legislation, and in particular the EU Water Framework Directive (WFD – 2000/60/EC), which deals with river basins, including estuaries and a narrow coastal strip, in order to examine these issues within the framework of integrated coastal zone management.
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TL;DR: In this article, the surface charges associated with the symmetries of asymptotically flat four dimensional spacetimes at null infinity are constructed, and they realize the symmetry algebra in general only up to a field-dependent central extension that satisfies a suitably generalized cocycle condition.
Abstract: The surface charges associated with the symmetries of asymptotically flat four dimensional spacetimes at null infinity are constructed. They realize the symmetry algebra in general only up to a field-dependent central extension that satisfies a suitably generalized cocycle condition. This extension vanishes when using the globally well defined BMS algebra. For the Kerr black hole and the enlarged BMS algebra with both supertranslations and superrotations, some of the supertranslation charges diverge whereas there are no divergences for the superrotation charges. The central extension is proportional to the rotation parameter and involves divergent integrals on the sphere.
TL;DR: The high hole mobility of a series of highly soluble diketo pyrrolo-pyrrole (DPP)-bithiophene copolymers may arise from the molecular packing feature common to the entire polymer series: backbones that are strictly oriented parallel to the substrate plane and coplanar with other backbones in the same layer.
Abstract: We describe a series of highly soluble diketo pyrrolo-pyrrole (DPP)-bithiophene copolymers exhibiting field effect hole mobilities up to 0.74 cm2 V–1 s–1, with a common synthetic motif of bulky 2-octyldodecyl side groups on the conjugated backbone. Spectroscopy, diffraction, and microscopy measurements reveal a transition in molecular packing behavior from a preferentially edge-on orientation of the conjugated plane to a preferentially face-on orientation as the attachment density of the side chains increases. Thermal annealing generally reduces both the face-on population and the misoriented edge-on domains. The highest hole mobilities of this series were obtained from edge-on molecular packing and in-plane liquid-crystalline texture, but films with a bimodal orientation distribution and no discernible in-plane texture exhibited surprisingly comparable mobilities. The high hole mobility may therefore arise from the molecular packing feature common to the entire polymer series: backbones that are strictly...
TL;DR: The complex geodomestication pathways that generated the vast range of banana cultivars (cvs) are clarified and several key stages of domestication for different cv groups are elucidated.
Abstract: Original multidisciplinary research hereby clarifies the complex geodomestication pathways that generated the vast range of banana cultivars (cvs). Genetic analyses identify the wild ancestors of modern-day cvs and elucidate several key stages of domestication for different cv groups. Archaeology and linguistics shed light on the historical roles of people in the movement and cultivation of bananas from New Guinea to West Africa during the Holocene. The historical reconstruction of domestication processes is essential for breeding programs seeking to diversify and improve banana cvs for the future.
University of Hamburg1, Thomas Jefferson University2, University of Texas MD Anderson Cancer Center3, University of Antwerp4, University of Bern5, Humboldt University of Berlin6, King's College London7, Université libre de Bruxelles8, Université catholique de Louvain9, Maastricht University10, University of Texas Southwestern Medical Center11, University of Turin12, Hannover Medical School13, Katholieke Universiteit Leuven14, University of Groningen15, Medical University of Graz16, University of Liverpool17, Boston University18, University of Reading19, Medical University of Vienna20, University of Upper Alsace21
TL;DR: The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients.
Abstract: The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.
TL;DR: It is proposed that due to their addictive properties, TA systems are likely to be maintained in chromosomes even though they do not necessarily confer an advantage to their bacterial hosts.
Abstract: Type II toxin-antitoxin (TA) systems are generally composed of two genes organized in an operon, encoding a labile antitoxin and a stable toxin. They were first discovered on plasmids where they contribute to plasmid stability by a phenomenon denoted as 'addiction', and subsequently in bacterial chromosomes. To discover novel families of antitoxins and toxins, we developed a bioinformatics approach based on the 'guilt by association' principle. Extensive experimental validation in Escherichia coli of predicted antitoxins and toxins increased significantly the number of validated systems and defined novel toxin and antitoxin families. Our data suggest that toxin families as well as antitoxin families originate from distinct ancestors that were assembled multiple times during evolution. Toxin and antitoxin families found on plasmids tend to be promiscuous and widespread, indicating that TA systems move through horizontal gene transfer. We propose that due to their addictive properties, TA systems are likely to be maintained in chromosomes even though they do not necessarily confer an advantage to their bacterial hosts. Therefore, addiction might play a major role in the evolutionary success of TA systems both on mobile genetic elements and in bacterial chromosomes.
TL;DR: In this paper, the surface composition and electronic structure of Au/TiO2 catalysts in comparison with TiO2 (anatase) and to reveal time-dependent X-ray irradiation damage of the samples.
Abstract: X-ray photoelectron spectroscopy (XPS) was employed to study the surface composition and electronic structure of Au/TiO2 catalysts in comparison with TiO2 (anatase) and to reveal time-dependent X-ray irradiation damage of the samples. The occurrence of Au nano-sized particles on a TiO2 support was found to result in a slight shift of Ti 2p core-level spectrum and in changes of the valence band and X-ray induced Auger spectra, compared to TiO2-only. It was shown that for different means of energy referencing the charge-corrected Au 4f7/2 binding energy in Au/TiO2 catalysts was 0.15–0.45 eV lower than that in pure bulk Au. Exposure to X-rays of Au/TiO2 catalysts and pure TiO2 caused a reduction of Ti 4+ oxidation state and desorption of oxygen from the surface. As a result, the surface chemical composition and electronic structure of the samples changed with time. The X-ray irradiation affected charge transfer processes in Au/TiO2 so that the pattern of X-ray induced damage in the Au-based catalyst turned out to be quite different from that in TiO2, with some characteristics displaying the very opposite features. Decreasing of the Au 4f7/2 binding energy and concurrent increasing of the fraction of Ti3+ species observed in the beginning of X-ray irradiation of Au/TiO2 may be taken as direct evidence for charge transfer from oxygen vacancies created by irradiation to Au particles.
TL;DR: This work shows that device-independent QKD is possible with key rates comparable to those of standard schemes, and provides a general security proof for a large class of protocols in a model in which the raw key is generated by independent measurements.
Abstract: Device-independent quantum key distribution (QKD) aims to provide key distribution schemes, the security of which is based on the laws of quantum physics, but which does not require any assumptions about the internal working of the devices used in the protocol. This strong form of security is possible only when using correlations that violate a Bell inequality. Here, we provide a general security proof for a large class of protocols in a model in which the raw key is generated by independent measurements. This independence condition may be justifiable in several implementations and is necessarily satisfied when the raw key is generated by N separate pairs of devices. Our work shows that device-independent QKD is possible with key rates comparable to those of standard schemes.
Norwegian Institute for Air Research1, Université libre de Bruxelles2, University of Cambridge3, Michigan Technological University4, Swiss Federal Laboratories for Materials Science and Technology5, German Aerospace Center6, University of Natural Resources and Life Sciences, Vienna7, University of Iceland8
TL;DR: In this article, an inversion scheme was used to estimate the volcanic ash source strength as a function of altitude and time, and the results showed that volcanic ash concentrations at some altitude in the atmosphere exceeded the limits for the "Normal" flying zone in up to 14 % (6-16 %), 2 % (1-3 %) and 7 % (4-11 %) of the European area.
Abstract: . The April–May, 2010 volcanic eruptions of Eyjafjallajokull, Iceland caused significant economic and social disruption in Europe whilst state of the art measurements and ash dispersion forecasts were heavily criticized by the aviation industry. Here we demonstrate for the first time that large improvements can be made in quantitative predictions of the fate of volcanic ash emissions, by using an inversion scheme that couples a priori source information and the output of a Lagrangian dispersion model with satellite data to estimate the volcanic ash source strength as a function of altitude and time. From the inversion, we obtain a total fine ash emission of the eruption of 8.3 ± 4.2 Tg for particles in the size range of 2.8–28 μm diameter. We evaluate the results of our model results with a posteriori ash emissions using independent ground-based, airborne and space-borne measurements both in case studies and statistically. Subsequently, we estimate the area over Europe affected by volcanic ash above certain concentration thresholds relevant for the aviation industry. We find that during three episodes in April and May, volcanic ash concentrations at some altitude in the atmosphere exceeded the limits for the "Normal" flying zone in up to 14 % (6–16 %), 2 % (1–3 %) and 7 % (4–11 %), respectively, of the European area. For a limit of 2 mg m−3 only two episodes with fractions of 1.5 % (0.2–2.8 %) and 0.9 % (0.1–1.6 %) occurred, while the current "No-Fly" zone criterion of 4 mg m−3 was rarely exceeded. Our results have important ramifications for determining air space closures and for real-time quantitative estimations of ash concentrations. Furthermore, the general nature of our method yields better constraints on the distribution and fate of volcanic ash in the Earth system.