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Showing papers by "Université catholique de Louvain published in 2009"


Journal ArticleDOI
23 Sep 2009-Nature
TL;DR: Identifying and quantifying planetary boundaries that must not be transgressed could help prevent human activities from causing unacceptable environmental change, argue Johan Rockstrom and colleagues.
Abstract: Identifying and quantifying planetary boundaries that must not be transgressed could help prevent human activities from causing unacceptable environmental change, argue Johan Rockstrom and colleagues.

8,837 citations


Journal ArticleDOI
TL;DR: Gmsh as mentioned in this paper is an open-source 3D finite element grid generator with a build-in CAD engine and post-processor that provides a fast, light and user-friendly meshing tool with parametric input and advanced visualization capabilities.
Abstract: Gmsh is an open-source 3-D finite element grid generator with a build-in CAD engine and post-processor. Its design goal is to provide a fast, light and user-friendly meshing tool with parametric input and advanced visualization capabilities. This paper presents the overall philosophy, the main design choices and some of the original algorithms implemented in Gmsh. Copyright (C) 2009 John Wiley & Sons, Ltd.

5,322 citations


Journal ArticleDOI
TL;DR: In this article, the authors proposed a new approach to global sustainability in which they define planetary boundaries within which they expect that humanity can operate safely. But the proposed concept of "planetary boundaries" lays the groundwork for shifting our approach to governance and management, away from the essentially sectoral analyses of limits to growth aimed at minimizing negative externalities, toward the estimation of the safe space for human development.
Abstract: Anthropogenic pressures on the Earth System have reached a scale where abrupt global environmental change can no longer be excluded. We propose a new approach to global sustainability in which we define planetary boundaries within which we expect that humanity can operate safely. Transgressing one or more planetary boundaries may be deleterious or even catastrophic due to the risk of crossing thresholds that will trigger non-linear, abrupt environmental change within continental- to planetary-scale systems. We have identified nine planetary boundaries and, drawing upon current scientific understanding, we propose quantifications for seven of them. These seven are climate change (CO2 concentration in the atmosphere <350 ppm and/or a maximum change of +1 W m-2 in radiative forcing); ocean acidification (mean surface seawater saturation state with respect to aragonite ≥ 80% of pre-industrial levels); stratospheric ozone (<5% reduction in O3 concentration from pre-industrial level of 290 Dobson Units); biogeochemical nitrogen (N) cycle (limit industrial and agricultural fixation of N2 to 35 Tg N yr-1) and phosphorus (P) cycle (annual P inflow to oceans not to exceed 10 times the natural background weathering of P); global freshwater use (<4000 km3 yr-1 of consumptive use of runoff resources); land system change (<15% of the ice-free land surface under cropland); and the rate at which biological diversity is lost (annual rate of <10 extinctions per million species). The two additional planetary boundaries for which we have not yet been able to determine a boundary level are chemical pollution and atmospheric aerosol loading. We estimate that humanity has already transgressed three planetary boundaries: for climate change, rate of biodiversity loss, and changes to the global nitrogen cycle. Planetary boundaries are interdependent, because transgressing one may both shift the position of other boundaries or cause them to be transgressed. The social impacts of transgressing boundaries will be a function of the social-ecological resilience of the affected societies. Our proposed boundaries are rough, first estimates only, surrounded by large uncertainties and knowledge gaps. Filling these gaps will require major advancements in Earth System and resilience science. The proposed concept of "planetary boundaries" lays the groundwork for shifting our approach to governance and management, away from the essentially sectoral analyses of limits to growth aimed at minimizing negative externalities, toward the estimation of the safe space for human development. Planetary boundaries define, as it were, the boundaries of the "planetary playing field" for humanity if we want to be sure of avoiding major human-induced environmental change on a global scale.

4,771 citations



Journal ArticleDOI
01 Aug 2009-Gut
TL;DR: It is found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP1-2-dependent mechanism, contributing to the improvement of Gut barrier functions during obesity and diabetes.
Abstract: BACKGROUND AND AIMS: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. METHODS: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. RESULTS: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. CONCLUSION: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.

2,127 citations


Journal ArticleDOI
TL;DR: This paper describes how to implement a new model, generate the Feynman rules, use a generic translation interface, and write a new translation interface.

1,068 citations


Book ChapterDOI
16 Apr 2009
TL;DR: In this paper, the authors propose a framework for the analysis of cryptographic implementations that includes a theoretical model and an application methodology based on commonly accepted hypotheses about side-channels that computations give rise to.
Abstract: The fair evaluation and comparison of side-channel attacks and countermeasures has been a long standing open question, limiting further developments in the field. Motivated by this challenge, this work makes a step in this direction and proposes a framework for the analysis of cryptographic implementations that includes a theoretical model and an application methodology. The model is based on commonly accepted hypotheses about side-channels that computations give rise to. It allows quantifying the effect of practically relevant leakage functions with a combination of information theoretic and security metrics, measuring the quality of an implementation and the strength of an adversary, respectively. From a theoretical point of view, we demonstrate formal connections between these metrics and discuss their intuitive meaning. From a practical point of view, the model implies a unified methodology for the analysis of side-channel key recovery attacks. The proposed solution allows getting rid of most of the subjective parameters that were limiting previous specialized and often ad hoc approaches in the evaluation of physically observable devices. It typically determines the extent to which basic (but practically essential) questions such as "How to compare two implementations? " or "How to compare two side-channel adversaries? " can be answered in a sound fashion.

934 citations


Journal ArticleDOI
TL;DR: Yambo is an ab initio code for calculating quasiparticle energies and optical properties of electronic systems within the framework of many-body perturbation theory and time-dependent density functional theory.

915 citations


Journal ArticleDOI
TL;DR: Data obtained in experimental models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate in the control of the development of metabolic diseases associated with obesity.
Abstract: Obesity is now classically characterized by a cluster of several metabolic disorders, and by a low grade inflammation. The evidence that the gut microbiota composition can be different between healthy and or obese and type 2 diabetic patients has led to the study of this environmental factor as a key link between the pathophysiology of metabolic diseases and the gut microbiota. Several mechanisms are proposed linking events occurring in the colon and the regulation of energy metabolism, such as i.e. the energy harvest from the diet, the synthesis of gut peptides involved in energy homeostasis (GLP-1, PYY...), and the regulation of fat storage. Moreover, the development of obesity and metabolic disorders following a high-fat diet may be associated to the innate immune system. Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex. Importantly, fat feeding is also associated with the development of metabolic endotoxemia in human subjects and participates in the low-grade inflammation, a mechanism associated with the development of atherogenic markers. Finally, data obtained in experimental models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate in the control of the development of metabolic diseases associated with obesity. Thus, it would be useful to find specific strategies for modifying gut microbiota to impact on the occurrence of metabolic diseases.

781 citations


Journal ArticleDOI
TL;DR: In patients with AML who are older than 60 years of age, escalation of the dose of daunorubicin to twice the conventional dose, with the entire dose administered in the first induction cycle, effects a more rapid response and a higher response rate than does the conventional doses, without additional toxic effects.
Abstract: BACKGROUND: A complete remission is essential for prolonging survival in patients with acute myeloid leukemia (AML). Daunorubicin is a cornerstone of the induction regimen, but the optimal dose is unknown. In older patients, it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter of body-surface area. METHODS: Patients in whom AML or high-risk refractory anemia had been newly diagnosed and who were 60 to 83 years of age (median, 67) were randomly assigned to receive cytarabine, at a dose of 200 mg per square meter by continuous infusion for 7 days, plus daunorubicin for 3 days, either at the conventional dose of 45 mg per square meter (411 patients) or at an escalated dose of 90 mg per square meter (402 patients); this treatment was followed by a second cycle of cytarabine at a dose of 1000 mg per square meter for 6 days. The primary end point was event-free survival. RESULTS: The complete remission rates were 64% in the group that received the escalated dose of daunorubicin and 54% in the group that received the conventional dose (P=0.002); the rates of remission after the first cycle of induction treatment were 52% and 35%, respectively (P<0.001). There was no significant difference between the two groups in the incidence of hematologic toxic effects, 30-day mortality (11% and 12% in the two groups, respectively), or the incidence of moderate, severe, or life-threatening adverse events (P=0.08). Survival end points in the two groups did not differ significantly overall, but patients in the escalated-treatment group who were 60 to 65 years of age, as compared with the patients in the same age group who received the conventional dose, had higher rates of complete remission (73% vs. 51%), event-free survival (29% vs. 14%), and overall survival (38% vs. 23%). CONCLUSIONS: In patients with AML who are older than 60 years of age, escalation of the dose of daunorubicin to twice the conventional dose, with the entire dose administered in the first induction cycle, effects a more rapid response and a higher response rate than does the conventional dose, without additional toxic effects. (Current Controlled Trials number, ISRCTN77039377; and Netherlands National Trial Register number, NTR212.)

759 citations



Journal ArticleDOI
TL;DR: Patients with APS still develop significant morbidity and mortality despite current treatment, and it is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.
Abstract: Objectives: To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance. Methods: The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed. Results: 200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected. Conclusion: Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).

Journal ArticleDOI
TL;DR: In this article, a new array-based method allowed screening of genome-wide copy number and loss of heterozygosity in single cells, which revealed not only mosaicism for whole-chromosome aneuploidies and uniparental disomies in most cleavage-stage embryos but also frequent segmental deletions, duplications and amplifications that were reciprocal in sister blastomeres, implying the occurrence of breakage-fusion-bridge cycles.
Abstract: Chromosome instability is a hallmark of tumorigenesis. This study establishes that chromosome instability is also common during early human embryogenesis. A new array-based method allowed screening of genome-wide copy number and loss of heterozygosity in single cells. This revealed not only mosaicism for whole-chromosome aneuploidies and uniparental disomies in most cleavage-stage embryos but also frequent segmental deletions, duplications and amplifications that were reciprocal in sister blastomeres, implying the occurrence of breakage-fusion-bridge cycles. This explains the low human fecundity and identifies post-zygotic chromosome instability as a leading cause of constitutional chromosomal disorders.

Journal ArticleDOI
TL;DR: Prebiotic supplementation was associated with an increase in plasma gut peptide concentrations (glucagon-like peptide 1 and peptide YY), which may contribute in part to changes in appetite sensation and glucose excursion responses after a meal in healthy subjects.

Journal ArticleDOI
TL;DR: A review of late-Holocene palaeoclimaoclimatology represents the results from a PAGES/CLIVAR Intersection Panel meeting that took place in June 2006 as mentioned in this paper, emphasizing current issues in their use for climate reconstruction; various approaches that have been adopted to combine multiple climate proxy records to provide estimates of past annual-to-decadal timescale Northern Hemisphere surface temperatures and other climate variables, such as large-scale circulation indices; and the forcing histories used in climate model simulations of the past millennium.
Abstract: This review of late-Holocene palaeoclimatology represents the results from a PAGES/CLIVAR Intersection Panel meeting that took place in June 2006. The review is in three parts: the principal high-resolution proxy disciplines (trees, corals, ice cores and documentary evidence), emphasizing current issues in their use for climate reconstruction; the various approaches that have been adopted to combine multiple climate proxy records to provide estimates of past annual-to-decadal timescale Northern Hemisphere surface temperatures and other climate variables, such as large-scale circulation indices; and the forcing histories used in climate model simulations of the past millennium. We discuss the need to develop a framework through which current and new approaches to interpreting these proxy data may be rigorously assessed using pseudo-proxies derived from climate model runs, where the `answer' is known. The article concludes with a list of recommendations. First, more raw proxy data are required from the diverse disciplines and from more locations, as well as replication, for all proxy sources, of the basic raw measurements to improve absolute dating, and to better distinguish the proxy climate signal from noise. Second, more effort is required to improve the understanding of what individual proxies respond to, supported by more site measurements and process studies. These activities should also be mindful of the correlation structure of instrumental data, indicating which adjacent proxy records ought to be in agreement and which not. Third, large-scale climate reconstructions should be attempted using a wide variety of techniques, emphasizing those for which quantified errors can be estimated at specified timescales. Fourth, a greater use of climate model simulations is needed to guide the choice of reconstruction techniques (the pseudo-proxy concept) and possibly help determine where, given limited resources, future sampling should be concentrated.

Journal ArticleDOI
TL;DR: A consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network forCSF biomarker research in multiple sclerosis, and focuses on CSf collection procedures, preanalytical factors, and high-quality clinical and paraclinical information.
Abstract: There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.

Journal ArticleDOI
TL;DR: The known short- and long-term mechanisms involved in the control of glucose and fatty acid utilization at the cytoplasmic and mitochondrial level in mammalian muscle and liver under normal and pathophysiological conditions are reviewed.
Abstract: In 1963, Lancet published a paper by Randle et al. that proposed a "glucose-fatty acid cycle" to describe fuel flux between and fuel selection by tissues. The original biochemical mechanism explained the inhibition of glucose oxidation by fatty acids. Since then, the principle has been confirmed by many investigators. At the same time, many new mechanisms controlling the utilization of glucose and fatty acids have been discovered. Here, we review the known short- and long-term mechanisms involved in the control of glucose and fatty acid utilization at the cytoplasmic and mitochondrial level in mammalian muscle and liver under normal and pathophysiological conditions. They include allosteric control, reversible phosphorylation, and the expression of key enzymes. However, the complexity is formidable. We suggest that not all chapters of the Randle cycle have been written.

Journal ArticleDOI
TL;DR: Revisions of the sensitivities of the RFCs to increases in GMT and a more thorough understanding of the concept of vulnerability that has evolved over the past 8 years are described.
Abstract: Article 2 of the United Nations Framework Convention on Climate Change [United Nations (1992) http://unfccc.int/resource/docs/convkp/conveng.pdf. Accessed February 9, 2009] commits signatory nations to stabilizing greenhouse gas concentrations in the atmosphere at a level that “would prevent dangerous anthropogenic interference (DAI) with the climate system.” In an effort to provide some insight into impacts of climate change that might be considered DAI, authors of the Third Assessment Report (TAR) of the Intergovernmental Panel on Climate Change (IPCC) identified 5 “reasons for concern” (RFCs). Relationships between various impacts reflected in each RFC and increases in global mean temperature (GMT) were portrayed in what has come to be called the “burning embers diagram.” In presenting the “embers” in the TAR, IPCC authors did not assess whether any single RFC was more important than any other; nor did they conclude what level of impacts or what atmospheric concentrations of greenhouse gases would constitute DAI, a value judgment that would be policy prescriptive. Here, we describe revisions of the sensitivities of the RFCs to increases in GMT and a more thorough understanding of the concept of vulnerability that has evolved over the past 8 years. This is based on our expert judgment about new findings in the growing literature since the publication of the TAR in 2001, including literature that was assessed in the IPCC Fourth Assessment Report (AR4), as well as additional research published since AR4. Compared with results reported in the TAR, smaller increases in GMT are now estimated to lead to significant or substantial consequences in the framework of the 5 “reasons for concern.”

Journal ArticleDOI
TL;DR: PTX-loaded nanoparticles showed greater tumor growth inhibition effect in vivo on TLT tumor, compared with Taxol, and may be considered as an effective anticancer drug delivery system for cancer chemotherapy.

Journal ArticleDOI
06 Apr 2009-Small
TL;DR: Exposure to silica nanoparticles causes cytotoxic damage and a decrease in cell survival in the EAHY926 cell line in a dose-related manner and the smaller particles appear to affect the exposed cells faster with cell death being observed within just a few hours.
Abstract: The effect that monodisperse amorphous spherical silica particles of different sizes have on the viability of endothelial cells (EAHY926 cell line) is investigated. The results indicate that exposure to silica nanoparticles causes cytotoxic damage (as indicated by lactate dehydrogenase (LDH) release) and a decrease in cell survival (as determined by the tetrazolium reduction, MTT, assay) in the EAHY926 cell line in a dose-related manner. Concentrations leading to a 50% reduction in cell viability (TC(50)) for the smallest particles tested (14-, 15-, and 16-nm diameter) ranging from 33 to 47 microg cm(-2) of cell culture differ significantly from values assessed for the bigger nanoparticles: 89 and 254 microg cm(-2) (diameter of 19 and 60 nm, respectively). Two fine silica particles with diameters of 104 and 335 nm show very low cytotoxic response compared to nanometer-sized particles with TC(50) values of 1095 and 1087 microg cm(-2), respectively. The smaller particles also appear to affect the exposed cells faster with cell death (by necrosis) being observed within just a few hours. The surface area of the tested particles is an important parameter in determining the toxicity of monodisperse amorphous silica nanoparticles.

Journal ArticleDOI
TL;DR: In this article, an integrative framework of corporate social responsibility (CSR) design and implementation is presented, which highlights four stages that span nine steps of the CSR design process.
Abstract: This article introduces an integrative framework of corporate social responsibility (CSR) design and implementation. A review of CSR literature in particular with regard to design and implementation models provides the background to develop a multiple case study. The resulting integrative framework, based on this multiple case study and Lewins change model, highlights four stages that span nine steps of the CSR design and implementation process. Finally, the study identifies critical success factors for the CSR process.

Journal ArticleDOI
TL;DR: This work analyzes the historical circumstances in which rising yields have been accompanied by declines in cultivated areas, thereby leading to land-sparing, and predicts future projections of cropland abandonment and ensuing environmental services cannot be assumed without explicit policy intervention.
Abstract: Does the intensification of agriculture reduce cultivated areas and, in so doing, spare some lands by concentrating production on other lands? Such sparing is important for many reasons, among them the enhanced abilities of released lands to sequester carbon and provide other environmental services. Difficulties measuring the extent of spared land make it impossible to investigate fully the hypothesized causal chain from agricultural intensification to declines in cultivated areas and then to increases in spared land. We analyze the historical circumstances in which rising yields have been accompanied by declines in cultivated areas, thereby leading to land-sparing. We use national-level United Nations Food and Agricultural Organization data on trends in cropland from 1970-2005, with particular emphasis on the 1990-2005 period, for 10 major crop types. Cropland has increased more slowly than population during this period, but paired increases in yields and declines in cropland occurred infrequently, both globally and nationally. Agricultural intensification was not generally accompanied by decline or stasis in cropland area at a national scale during this time period, except in countries with grain imports and conservation set-aside programs. Future projections of cropland abandonment and ensuing environmental services cannot be assumed without explicit policy intervention.

Journal ArticleDOI
TL;DR: Phylogenetic analysis of the ABC pleiotropic drug resistance family has provided a new view of the evolution of this important class of efflux pumps, and potential therapeutic approaches that could overcome azole resistance are proposed.
Abstract: Fungi cause serious infections in the immunocompromised and debilitated, and the incidence of invasive mycoses has increased significantly over the last 3 decades. Slow diagnosis and the relatively few classes of antifungal drugs result in high attributable mortality for systemic fungal infections. Azole antifungals are commonly used for fungal infections, but azole resistance can be a problem for some patient groups. High-level, clinically significant azole resistance usually involves overexpression of plasma membrane efflux pumps belonging to the ATP-binding cassette (ABC) or the major facilitator superfamily class of transporters. The heterologous expression of efflux pumps in model systems, such Saccharomyces cerevisiae, has enabled the functional analysis of efflux pumps from a variety of fungi. Phylogenetic analysis of the ABC pleiotropic drug resistance family has provided a new view of the evolution of this important class of efflux pumps. There are several ways in which the clinical significance of efflux-mediated antifungal drug resistance can be mitigated. Alternative antifungal drugs, such as the echinocandins, that are not efflux pump substrates provide one option. Potential therapeutic approaches that could overcome azole resistance include targeting efflux pump transcriptional regulators and fungal stress response pathways, blockade of energy supply, and direct inhibition of efflux pumps.

Journal ArticleDOI
TL;DR: In this paper, the authors simulate the Holocene thermal maximum in a coupled global ocean-atmosphere-vegetation model and find that before 7,000 years ago, summers were substantially cooler over regions directly influenced by the presence of the Laurentide ice sheet.
Abstract: The Holocene thermal maximum, a period of relatively warm climate between 11,000 and 5,000 years ago1, 2, is most clearly recorded in the middle and high latitudes2, 3 of the Northern Hemisphere, where it is generally associated with the local orbitally forced summer insolation maximum. However, proxy-based reconstructions have shown that both the timing and magnitude of the warming vary substantially between different regions2, 3, 4, suggesting the involvement of extra feedbacks and forcings. Here, we simulate the Holocene thermal maximum in a coupled global ocean–atmosphere–vegetation model. We find that before 7,000 years ago, summers were substantially cooler over regions directly influenced by the presence of the Laurentide ice sheet, whereas other regions of the Northern Hemisphere were dominated by orbital forcing. Our simulations suggest that the cool conditions arose from a combination of the inhibition of Labrador Sea deep convection by the flux of meltwater from the ice sheet, which weakened northward heat transport by the ocean, and the high surface albedo of the ice sheet. We thus conclude that interglacial climate is highly sensitive to relatively small changes in ice-sheet configuration.

Journal ArticleDOI
TL;DR: It is demonstrated that high-density arrays of nanostructures of a ferroelectric polymer can be easily fabricated by a simple nano-embossing protocol, with integration densities larger than 33 Gbits inch(-2).
Abstract: Ferroelectric nanostructures are attracting tremendous interest because they offer a promising route to novel integrated electronic devices such as non-volatile memories and probe-based mass data storage. Here, we demonstrate that high-density arrays of nanostructures of a ferroelectric polymer can be easily fabricated by a simple nano-embossing protocol, with integration densities larger than 33 Gbits inch(-2). The orientation of the polarization axis, about which the dipole moment rotates, is simultaneously aligned in plane over the whole patterned region. Internal structural defects are significantly eliminated in the nanostructures. The improved crystal orientation and quality enable well-defined uniform switching behaviour from cell to cell. Each nanocell shows a narrow and almost ideal square-shaped hysteresis curve, with low energy losses and a coercive field of approximately 10 MV m(-1), well below previously reported bulk values. These results pave the way to the fabrication of soft plastic memories compatible with all-organic electronics and low-power information technology.

Journal ArticleDOI
TL;DR: In this article, a controlled experimental design was used to investigate whether it is possible to increase emotional intelligence (EI) by using a brief empirically-derived EI training session while the control participants continued to live normally.

Journal ArticleDOI
TL;DR: Combination with radiotherapy renders remaining cells more sensitive to irradiation, emphasizing how interference with tumor cell metabolism may complement current anticancer modalities.

Journal ArticleDOI
TL;DR: These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee and includes an update in the light of advances in PET technology, the introduction of hybrid PET/CT systems and the broadening clinical indications for FDG brain imaging.
Abstract: These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting the results of fluorine-18 fluoro-2-deoxyglucose ([(18)F]FDG) PET imaging of the brain. The aim is to help achieve a high standard of FDG imaging, which will increase the diagnostic impact of this technique in neurological and psychiatric practice. The present document replaces a former version of the guidelines that were published in 2002 [1] and includes an update in the light of advances in PET technology, the introduction of hybrid PET/CT systems and the broadening clinical indications for FDG brain imaging. These guidelines are intended to present information specifically adapted for European practice. The information provided should be taken in the context of local conditions and regulations.

Journal ArticleDOI
TL;DR: The continuum of the influence of eNOS in cardiovascular biology explains its growing implication in mechanosensitive aspects of integrated physiology, such as the control of blood pressure variability or the modulation of cardiac remodeling in situations of hemodynamic overload.
Abstract: Nitric oxide production in response to flow-dependent shear forces applied on the surface of endothelial cells is a fundamental mechanism of regulation of vascular tone, peripheral resistance, and tissue perfusion. This implicates the concerted action of multiple upstream "mechanosensing" molecules reversibly assembled in signalosomes recruiting endothelial nitric oxide synthase (eNOS) in specific subcellular locales, e.g., plasmalemmal caveolae. Subsequent short- and long-term increases in activity and expression of eNOS translate this mechanical stimulus into enhanced NO production and bioactivity through a complex transcriptional and posttranslational regulation of the enzyme, including by shear-stress responsive transcription factors, oxidant stress-dependent regulation of transcript stability, eNOS regulatory phosphorylations, and protein-protein interactions. Notably, eNOS expressed in cardiac myocytes is amenable to a similar regulation in response to stretching of cardiac muscle cells and in part mediates the length-dependent increase in cardiac contraction force. In addition to short-term regulation of contractile tone, eNOS mediates key aspects of cardiac and vascular remodeling, e.g., by orchestrating the mobilization, recruitment, migration, and differentiation of cardiac and vascular progenitor cells, in part by regulating the stabilization and transcriptional activity of hypoxia inducible factor in normoxia and hypoxia. The continuum of the influence of eNOS in cardiovascular biology explains its growing implication in mechanosensitive aspects of integrated physiology, such as the control of blood pressure variability or the modulation of cardiac remodeling in situations of hemodynamic overload.

Journal ArticleDOI
TL;DR: How atomic force microscopy can be applied to force probe surfaces of living cells to single-molecule resolution is reviewed to provide unique insight into how cells structurally and functionally modulate the molecules of their surfaces to interact with the cellular environment.
Abstract: Biological processes rely on molecular interactions that can be directly measured using force spectroscopy techniques. Here we review how atomic force microscopy can be applied to force probe surfaces of living cells to single-molecule resolution. Such probing of individual interactions can be used to map cell surface receptors, and to assay the receptors' functional states, binding kinetics and landscapes. This information provides unique insight into how cells structurally and functionally modulate the molecules of their surfaces to interact with the cellular environment.