Showing papers by "Université catholique de Louvain published in 2013"

Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

Abstract: Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.

Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer

Abstract: BACKGROUND: Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor (EGFR) therapy. Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy. METHODS: In this prospective-retrospective analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS (KRAS or NRAS) or BRAF mutation status. A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon 15. The overall rate of ascertainment of RAS status was 90%. RESULTS: Among 512 patients without RAS mutations, progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone (hazard ratio for progression or death with combination therapy, 0.72; 95% confidence interval [CI], 0.58 to 0.90; P = 0.004). Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group (hazard ratio for death, 0.78; 95% CI, 0.62 to 0.99; P = 0.04). A total of 108 patients (17%) with non-mutated KRAS exon 2 had other RAS mutations. These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2. BRAF mutations were a negative prognostic factor. No new safety signals were identified. CONCLUSIONS: Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy

Long-term Climate Change: Projections, Commitments and Irreversibility

Abstract: This chapter assesses long-term projections of climate change for the end of the 21st century and beyond, where the forced signal depends on the scenario and is typically larger than the internal variability of the climate system. Changes are expressed with respect to a baseline period of 1986–2005, unless otherwise stated.

Climate change projections using the IPSL-CM5 Earth System Model: From CMIP3 to CMIP5

Abstract: We present the global general circulation model IPSL-CM5 developed to study the long-term response of the climate system to natural and anthropogenic forcings as part of the 5th Phase of the Coupled Model Intercomparison Project (CMIP5). This model includes an interactive carbon cycle, a representation of tropospheric and stratospheric chemistry, and a comprehensive representation of aerosols. As it represents the principal dynamical, physical, and bio-geochemical processes relevant to the climate system, it may be referred to as an Earth System Model. However, the IPSL-CM5 model may be used in a multitude of configurations associated with different boundary conditions and with a range of complexities in terms of processes and interactions. This paper presents an overview of the different model components and explains how they were coupled and used to simulate historical climate changes over the past 150 years and different scenarios of future climate change. A single version of the IPSL-CM5 model (IPSL-CM5A-LR) was used to provide climate projections associated with different socio-economic scenarios, including the different Representative Concentration Pathways considered by CMIP5 and several scenarios from the Special Report on Emission Scenarios considered by CMIP3. Results suggest that the magnitude of global warming projections primarily depends on the socio-economic scenario considered, that there is potential for an aggressive mitigation policy to limit global warming to about two degrees, and that the behavior of some components of the climate system such as the Arctic sea ice and the Atlantic Meridional Overturning Circulation may change drastically by the end of the twenty-first century in the case of a no climate policy scenario. Although the magnitude of regional temperature and precipitation changes depends fairly linearly on the magnitude of the projected global warming (and thus on the scenario considered), the geographical pattern of these changes is strikingly similar for the different scenarios. The representation of atmospheric physical processes in the model is shown to strongly influence the simulated climate variability and both the magnitude and pattern of the projected climate changes.

Crowdfunding: Tapping the Right Crowd

Abstract: With crowdfunding, an entrepreneur raises external financing from a large audience (the "crowd"), in which each individual provides a very small amount, instead of soliciting a small group of sophisticated investors. This article compares two forms of crowdfunding: entrepreneurs solicit individuals either to pre-order the product or to advance a fixed amount of money in exchange for a share of future profits (or equity). In either case, we assume that "crowdfunders" enjoy "community benefits" that increase their utility. Using a unified model, we show that the entrepreneur prefers pre-ordering if the initial capital requirement is relatively small compared with market size and prefers profit sharing otherwise. Our conclusions have implications for managerial decisions in the early development stage of firms, when the entrepreneur needs to build a community of individuals with whom he or she must interact. We also offer extensions on the impact of quality uncertainty and information asymmetry.

Unique in the Crowd: The privacy bounds of human mobility

Abstract: We study fifteen months of human mobility data for one and a half million individuals and find that human mobility traces are highly unique. In fact, in a dataset where the location of an individual is specified hourly, and with a spatial resolution equal to that given by the carrier’s antennas, four spatio-temporal points are enough to uniquely identify 95% of the individuals. We coarsen the data spatially and temporally to find a formula for the uniqueness of human mobility traces given their resolution and the available outside information. This formula shows that the uniqueness of mobility traces decays approximately as the 1/10 power of their resolution. Hence, even coarse datasets provide little anonymity. These findings represent fundamental constraints to an individual’s privacy and have important implications for the design of frameworks and institutions dedicated to protect the privacy of individuals.

Identification of individual and few layers of WS2 using Raman Spectroscopy

Abstract: The Raman scattering of single- and few-layered WS2 is studied as a function of the number of S-W-S layers and the excitation wavelength in the visible range (488, 514 and 647 nm). For the three excitation wavelengths used in this study, the frequency of the A1g(Γ) phonon mode monotonically decreases with the number of layers. For single-layer WS2, the 514.5 nm laser excitation generates a second-order Raman resonance involving the longitudinal acoustic mode (LA(M)). This resonance results from a coupling between the electronic band structure and lattice vibrations. First-principles calculations were used to determine the electronic and phonon band structures of single-layer and bulk WS2. The reduced intensity of the 2LA mode was then computed, as a function of the laser wavelength, from the fourth-order Fermi golden rule. Our observations establish an unambiguous and nondestructive Raman fingerprint for identifying single- and few-layered WS2 films.

Polymer/carbon based composites as electromagnetic interference (EMI) shielding materials

Abstract: The extensive development of electronic systems and telecommunications has lead to major concerns regarding electromagnetic pollution. Motivated by environmental questions and by a wide variety of applications, the quest for materials with high efficiency to mitigate electromagnetic interferences (EMI) pollution has become a mainstream field of research. This paper reviews the state-of-the-art research in the design and characterization of polymer/carbon based composites as EMI shielding materials. After a brief introduction, in Section 1, the electromagnetic theory will be briefly discussed in Section 2 setting the foundations of the strategies to be employed to design efficient EMI shielding materials. These materials will be classified in the next section by the type of carbon fillers, involving carbon black, carbon fiber, carbon nanotubes and graphene. The importance of the dispersion method into the polymer matrix (melt-blending, solution processing, etc.) on the final material properties will be discussed. The combination of carbon fillers with other constituents such as metallic nanoparticles or conductive polymers will be the topic of Section 4. The final section will address advanced complex architectures that are currently studied to improve the performances of EMI materials and, in some cases, to impart additional properties such as thermal management and mechanical resistance. In all these studies, we will discuss the efficiency of the composites/devices to absorb and/or reflect the EMI radiation.

Continental-scale temperature variability during the past two millennia

Abstract: Past global climate changes had strong regional expression To elucidate their spatio-temporal pattern, we reconstructed past temperatures for seven continental-scale regions during the past one to two millennia The most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century At multi-decadal to centennial scales, temperature variability shows distinctly different regional patterns, with more similarity within each hemisphere than between them There were no globally synchronous multi-decadal warm or cold intervals that define a worldwide Medieval Warm Period or Little Ice Age, but all reconstructions show generally cold conditions between ad 1580 and 1880, punctuated in some regions by warm decades during the eighteenth century The transition to these colder conditions occurred earlier in the Arctic, Europe and Asia than in North America or the Southern Hemisphere regions Recent warming reversed the long-term cooling; during the period ad 1971–2000, the area-weighted average reconstructed temperature was higher than any other time in nearly 1,400 years

Robust 1-Bit Compressive Sensing via Binary Stable Embeddings of Sparse Vectors

Abstract: The compressive sensing (CS) framework aims to ease the burden on analog-to-digital converters (ADCs) by reducing the sampling rate required to acquire and stably recover sparse signals. Practical ADCs not only sample but also quantize each measurement to a finite number of bits; moreover, there is an inverse relationship between the achievable sampling rate and the bit depth. In this paper, we investigate an alternative CS approach that shifts the emphasis from the sampling rate to the number of bits per measurement. In particular, we explore the extreme case of 1-bit CS measurements, which capture just their sign. Our results come in two flavors. First, we consider ideal reconstruction from noiseless 1-bit measurements and provide a lower bound on the best achievable reconstruction error. We also demonstrate that i.i.d. random Gaussian matrices provide measurement mappings that, with overwhelming probability, achieve nearly optimal error decay. Next, we consider reconstruction robustness to measurement errors and noise and introduce the binary e-stable embedding property, which characterizes the robustness of the measurement process to sign changes. We show that the same class of matrices that provide almost optimal noiseless performance also enable such a robust mapping. On the practical side, we introduce the binary iterative hard thresholding algorithm for signal reconstruction from 1-bit measurements that offers state-of-the-art performance.

Observation of a new boson with mass near 125 GeV in pp collisions at $ \sqrt{s}=7 $ and 8 TeV

Abstract: A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 inverse femtobarns at sqrt(s) = 7 TeV, and up to 5.3 inverse femtobarns at sqrt(s) = 8 TeV. The results for five Higgs boson decay modes gamma gamma, ZZ, WW, tau tau, and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, gamma gamma and ZZ to 4 ell, gives a mass estimate of 125.3 +/- 0.4 (stat) +/- 0.5 (syst) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.

Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women

Abstract: Objective To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese women. Methods A double blind, placebo controlled, intervention study was performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose 50/50 mix; n=15) or placebo (maltodextrin; n=15) for 3 months (16 g/day). Blood, faeces and urine sampling, oral glucose tolerance test, homeostasis model assessment and impedancemetry were performed before and after treatment. The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA. Plasma and urine metabolic profiles were analysed by 1 H-NMR spectroscopy. Results Treatment with ITF prebiotics, but not the placebo, led to an increase in Bifidobacterium and Faecalibacterium prausnitzii; both bacteria negatively correlated with serum lipopolysaccharide levels. ITF prebiotics also decreased Bacteroides intestinalis, Bacteroides vulgatus and Propionibacterium, an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels. No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses. However, ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and/or diabetes. Conclusions ITF prebiotics selectively changed the gut microbiota composition in obese women, leading to modest changes in host metabolism, as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures.

Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial.

Abstract: Importance Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response. Objective To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality. Design, Setting, and Participants We performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. Interventions Patients with severe sepsis (n = 1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2:1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo, with n = 1304 and n = 657 patients, respectively. Main Outcome Measures The primary end point was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months after beginning treatment. Results Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P = .59; hazard ratio, 1.05; 95% CI, 0.88-1.26; difference in mortality rate, −1.1; 95% CI, −5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P = .79 (hazard ratio, 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. Conclusions and Relevance Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality. Trial Registration clinicaltrials.gov Identifier: NCT00334828

More Than Words: The Influence of Affective Content and Linguistic Style Matches in Online Reviews on Conversion Rates

Abstract: Customers increasingly rely on other consumers' reviews to make purchase decisions online. New insights into the customer review phenomenon can be derived from studying the semantic content and style properties of verbatim customer reviews to examine their influence on online retail sites' conversion rates. The authors employ text mining to extract changes in affective content and linguistic style properties of customer book reviews on Amazon.com. A dynamic panel data model reveals that the influence of positive affective content on conversion rates is asymmetrical, such that greater increases in positive affective content in customer reviews have a smaller effect on subsequent increases in conversion rate. No such tapering-off effect occurs for changes in negative affective content in reviews. Furthermore, positive changes in affective cues and increasing congruence with the product interest group's typical linguistic style directly and conjointly increase conversion rates. These findings suggest that managers should identify and promote the most influential reviews in a given product category, provide instructions to stimulate reviewers to write powerful reviews, and adapt the style of their own editorial reviews to the relevant product category.

Identification and design principles of low hole effective mass p -type transparent conducting oxides

Abstract: The development of high-performance transparent conducting oxides is critical to many technologies from transparent electronics to solar cells. Whereas n-type transparent con- ducting oxides are present in many devices, their p-type counterparts are not largely com- mercialized, as they exhibit much lower carrier mobilities due to the large hole effective masses of most oxides. Here we conduct a high-throughput computational search on thousands of binary and ternary oxides and identify several highly promising compounds displaying exceptionally low hole effective masses (up to an order of magnitude lower than state-of-the-art p-type transparent conducting oxides), as well as wide band gaps. In addition to the discovery of specific compounds, the chemical rationalization of our findings opens new directions, beyond current Cu-based chemistries, for the design and development of future p-type transparent conducting oxides.

Individual dispersal, landscape connectivity and ecological networks.

Abstract: Connectivity is classically considered an emergent property of landscapes encapsulating individuals’ flows across space. However, its operational use requires a precise understanding of why and how organisms disperse. Such movements, and hence landscape connectivity, will obviously vary according to both organism properties and landscape features. We review whether landscape connectivity estimates could gain in both precision and generality by incorporating three fundamental outcomes of dispersal theory. Firstly, dispersal is a multi-causal process; its restriction to an ‘escape reaction’ to environmental unsuitability is an oversimplification, as dispersing individuals can leave excellent quality habitat patches or stay in poor-quality habitats according to the relative costs and benefits of dispersal and philopatry. Secondly, species, populations and individuals do not always react similarly to those cues that trigger dispersal, which sometimes results in contrasting dispersal strategies. Finally, dispersal is a major component of fitness and is thus under strong selective pressures, which could generate rapid adaptations of dispersal strategies. Such evolutionary responses will entail spatiotemporal variation in landscape connectivity. We thus strongly recommend the use of genetic tools to: (i) assess gene flow intensity and direction among populations in a given landscape; and (ii) accurately estimate landscape features impacting gene flow, and hence landscape connectivity. Such approaches will provide the basic data for planning corridors or stepping stones aiming at (re)connecting local populations of a given species in a given landscape. This strategy is clearly species- and landscape-specific. But we suggest that the ecological network in a given landscape could be designed by stacking up such linkages designed for several species living in different ecosystems. This procedure relies on the use of umbrella species that are representative of other species living in the same ecosystem.

Diabetes, obesity and gut microbiota.

Abstract: The gut microbiota composition has been associated with several hallmarks of metabolic syndrome (e.g., obesity, type 2 diabetes, cardiovascular diseases, and non-alcoholic steatohepatitis). Growing evidence suggests that gut microbes contribute to the onset of the low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. Recently, enteroendocrine cells and the endocannabinoid system have been shown to control gut permeability and metabolic endotoxaemia. Moreover, targeted nutritional interventions using non-digestible carbohydrates with prebiotic properties have shown promising results in pre-clinical studies in this context, although human intervention studies warrant further investigations. Thus, in this review, we discuss putative mechanisms linking gut microbiota and type 2 diabetes. These data underline the advantage of investigating and changing the gut microbiota as a therapeutic target in the context of obesity and type 2 diabetes.

EANM/SNMMI Guideline for 18F-FDG Use in Inflammation and Infection

Abstract: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology and practical application of nuclear medicine. Its 16,000 members are physicians, technologists, and scientists specializing

Weights in Multidimensional Indices of Wellbeing: An Overview

Abstract: Multidimensional indices are becoming increasingly important instruments to assess the wellbeing of societies. They move beyond the focus on a single indicator and yet they are easy to present and communicate. A crucial step in the construction of a multidimensional index of wellbeing is the selection of the relative weights for the different dimensions. The aim of this article is to study the role of these weights and to critically survey eight different approaches to set them. We categorize the approaches in three classes: data-driven, normative, and hybrid weighting, and compare their respective advantages and drawbacks.

Photo-responsive block copolymer micelles: design and behavior

Abstract: Stimuli-responsive block copolymer micelles are the topic of intense research since they are able to show sharp and eventually reversible responses to various environmental changes and find applications in various fields including controlled drug delivery. Among all the available stimuli, light has recently attracted much attention since it can be localized in time and space, and it can also be triggered from outside of the system. In this tutorial review, we highlight the progress realized in recent years. More precisely, we provide some guidelines towards the rational design of photo-responsive block copolymers and we present the different photo-responsive moieties that have been used so far. We also discuss the different types of irreversible and reversible responses encountered by photo-responsive block copolymer micelles. Finally, we suggest possible future developments including the design of biocompatible systems operating at excitation wavelengths compatible for biomedical applications.

JAK/STAT signaling in hematological malignancies

Abstract: The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by cytokine receptors, a superfamily of more than 30 transmembrane proteins that recognize specific cytokines, and is critical in blood formation and immune response. Many of those receptors transmit anti-apoptotic, proliferative and differentiation signals, and their expression and functions are critical for the formation of blood lineages. Several cancers, including blood malignancies, have been associated with constitutive activation of members of the STAT family, which normally require JAK-mediated tyrosine phosphorylation for transcriptional activation. More recently, human myeloproliferative neoplasms were discovered to be associated with a unique acquired somatic mutation in JAK2 (JAK2 V617F), rare exon 12 JAK2 mutations, or thrombopoietin receptor mutations that constitutively activate wild-type JAK2. Prompted by these observations, many studies have explored the possibility that JAKs, cytokine receptors, or other components of the JAK/STAT pathway are mutated or upregulated in several hematological malignancies. This has been observed in certain pediatric acute lymphoblastic leukemias and adult T-cell lymphoblastic leukemias, and overexpression of JAK2 seems to be important in Hodgkin lymphoma. Here we discuss the nature and respective contribution of mutations dysregulating the JAK/STAT pathway in hematological malignancies and present examples in which such mutations drive the disease, contribute to the phenotype, or provide a survival and proliferative advantage. JAK inhibitors are making their way into the therapeutic arsenal (for example, in myelofibrosis), and we discuss the possibility that other hematological diseases might benefit from treatment with these inhibitors in combination with other agents.