Showing papers by "University of Geneva published in 2002"
TL;DR: The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
Abstract: The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.
6,643 citations
TL;DR: It is clear that the understanding of the myofibroblast — its origins, functions and molecular regulation — will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
Abstract: During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
3,836 citations
TL;DR: The Guideline for Hand Hygiene in Health-Care Settings provides health-care workers (HCWs) with a review of data regarding handwashing and hand antisepsis and provides specific recommendations to promote improved hand-hygiene practices and reduce transmission of pathogenic microorganisms to patients and personnel in health- Care settings.
2,882 citations
TL;DR: The orphan nuclear receptor REV-ERBalpha is identified as the major regulator of cyclic Bmal1 transcription, and constitutes a molecular link through which components of the negative limb drive antiphasic expression of component of the positive limb.
2,052 citations
TL;DR: The samova algorithm was applied to a set of European roe deer populations examined for their mitochondrial DNA (mtDNA) HVRI diversity and the inferred genetic structure seemed to confirm the hypothesis that some Italian populations were recently reintroduced from a Balkanic stock.
Abstract: We present a new approach for defining groups of populations that are geographically homogeneous and maximally differentiated from each other. As a by-product, it also leads to the identification of genetic barriers between these groups. The method is based on a simulated annealing procedure that aims to maximize the proportion of total genetic variance due to differences between groups of populations (spatial analysis of molecular variance; samova). Monte Carlo simulations were used to study the performance of our approach and, for comparison, the behaviour of the Monmonier algorithm, a procedure commonly used to identify zones of sharp genetic changes in a geographical area. Simulations showed that the samova algorithm indeed finds maximally differentiated groups, which do not always correspond to the simulated group structure in the presence of isolation by distance, especially when data from a single locus are available. In this case, the Monmonier algorithm seems slightly better at finding predefined genetic barriers, but can often lead to the definition of groups of populations not differentiated genetically. The samova algorithm was then applied to a set of European roe deer populations examined for their mitochondrial DNA (mtDNA) HVRI diversity. The inferred genetic structure seemed to confirm the hypothesis that some Italian populations were recently reintroduced from a Balkanic stock, as well as the differentiation of groups of populations possibly due to the postglacial recolonization of Europe or the action of a specific barrier to gene flow.
1,831 citations
TL;DR: Histone H3 methylated in vitro by the E(Z)/ESC complex binds specifically to Polycomb protein, which is closely associated with Polycomb binding sites on polytene chromosomes but is also found in centric heterochromatin, chromosome 4, and telomeric sites.
1,540 citations
TL;DR: In this article, a new program is developed for ab initio crystal structure determination from powder diffraction data (X-ray and neutron) using global optimization algorithms to solve the structure by performing trials in direct space.
Abstract: A new program has been developed for ab initio crystal structure determination from powder diffraction data (X-ray and neutron). It uses global-optimization algorithms to solve the structure by performing trials in direct space. It is a modular program, capable of using several criteria for evaluating each trial configuration (e.g. multi-pattern). It is also modular in the description of the crystal content, with the possibility of describing building blocks in the sample, such as polyhedra or molecules, and with automatic adaptive handling of special positions and sharing of identical atoms between neighbouring building blocks. It can therefore find the correct structure without any assumption about the connectivity of the building blocks and is suitable for any kind of material. Several optimization algorithms (simulated annealing, parallel tempering) are available, with the possibility of choosing the convergence criterion as a combination of available cost functions. This program is freely available for Linux and Windows platforms; it is also fully `open source', which, combined with an object-oriented design and a complete developer documentation, ensures its future evolution.
1,209 citations
TL;DR: The information gained by a potential eavesdropper applying a cloning-based individual attack is derived, along with an upper bound on the error rate that ensures unconditional security against coherent attacks.
Abstract: We consider two quantum cryptographic schemes relying on encoding the key into qudits, i.e., quantum states in a d-dimensional Hilbert space. The first cryptosystem uses two mutually unbiased bases (thereby extending the BB84 scheme), while the second exploits all d+1 available such bases (extending the six-state protocol for qubits). We derive the information gained by a potential eavesdropper applying a cloning-based individual attack, along with an upper bound on the error rate that ensures unconditional security against coherent attacks.
1,188 citations
TL;DR: In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1beta, followed by NF-kappaB activation, Fas upregulation, DNA fragmentation, and impaired beta cell function, which implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes.
Abstract: In type 2 diabetes, chronic hyperglycemia is suggested to be detrimental to pancreatic beta cells, causing impaired insulin secretion. IL-1beta is a proinflammatory cytokine acting during the autoimmune process of type 1 diabetes. IL-1beta inhibits beta cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor NF-kappaB. Recently, we have shown that increased glucose concentrations also induce Fas expression and beta cell apoptosis in human islets. The aim of the present study was to test the hypothesis that IL-1beta may mediate the deleterious effects of high glucose on human beta cells. In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1beta, followed by NF-kappaB activation, Fas upregulation, DNA fragmentation, and impaired beta cell function. The IL-1 receptor antagonist protected cultured human islets from these deleterious effects. beta cells themselves were identified as the islet cellular source of glucose-induced IL-1beta. In vivo, IL-1beta-producing beta cells were observed in pancreatic sections of type 2 diabetic patients but not in nondiabetic control subjects. Similarly, IL-1beta was induced in beta cells of the gerbil Psammomys obesus during development of diabetes. Treatment of the animals with phlorizin normalized plasma glucose and prevented beta cell expression of IL-1beta. These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1beta/NF-kappaB pathway as a target to preserve beta cell mass and function in this condition.
1,105 citations
TL;DR: PlGF stimulated angiogenesis and collateral growth in ischemic heart and limb with at least a comparable efficiency to vascular endothelial growth factor (VEGF) and an antibody against Flt1 suppressed neovascularization in tumors and isChemic retina, and angiogenic and inflammatory joint destruction in autoimmune arthritis.
Abstract: The therapeutic potential of placental growth factor (PlGF) and its receptor Flt1 in angiogenesis is poorly understood. Here, we report that PlGF stimulated angiogenesis and collateral growth in ischemic heart and limb with at least a comparable efficiency to vascular endothelial growth factor (VEGF). An antibody against Flt1 suppressed neovascularization in tumors and ischemic retina, and angiogenesis and inflammatory joint destruction in autoimmune arthritis. Anti-Flt1 also reduced atherosclerotic plaque growth and vulnerability, but the atheroprotective effect was not attributable to reduced plaque neovascularization. Inhibition of VEGF receptor Flk1 did not affect arthritis or atherosclerosis, indicating that inhibition of Flk1-driven angiogenesis alone was not sufficient to halt disease progression. The anti-inflammatory effects of anti-Flt1 were attributable to reduced mobilization of bone marrow-derived myeloid progenitors into the peripheral blood; impaired infiltration of Flt1-expressing leukocytes in inflamed tissues; and defective activation of myeloid cells. Thus, PlGF and Flt1 constitute potential candidates for therapeutic modulation of angiogenesis and inflammation.
1,100 citations
TL;DR: Antimony is ubiquitously present in the environment as a result of natural processes and human activities as discussed by the authors and is considered to be priority pollutants interest by the USEPA and the EU.
Council on Education for Public Health1, Cancer Research UK2, French Institute of Health and Medical Research3, Peking Union Medical College4, Chinese Academy of Sciences5, University of Geneva6, National Cancer Research Institute7, Temple University8, University of Los Andes9, Florida International University10, Harbin Medical University11, Yale University12, Stanford University13, University of Turin14, Marshfield Clinic15
TL;DR: A resource of 1064 cultured lymphoblastoid cell lines from individuals in different world populations and corresponding milligram quantities of DNA is deposited at the Foundation Jean Dausset (CEPH) in Paris.
Abstract: A resource of 1064 cultured lymphoblastoid cell lines (LCLs) ([1][1]) from individuals in different world populations and corresponding milligram quantities of DNA is deposited at the Foundation Jean Dausset (CEPH) ([2][2]) in Paris. LCLs were collected from various laboratories by the Human Genome
TL;DR: Different strategies, including polymer-PS conjugation or encapsulation of the drug in colloidal carriers such as oil-dispersions, liposomes and polymeric particles, have been investigated to improve tumour targeting and to minimize the side effects.
Abstract: In photodynamic therapy, one of the problems limiting the use of many photosensitizers (PS) is the difficulty in preparing pharmaceutical formulations that enable their parenteral administration. Due to their low water solubility, the hydrophobic PS cannot be simply injected intravenously. Different strategies, including polymer-PS conjugation or encapsulation of the drug in colloidal carriers such as oil-dispersions, liposomes and polymeric particles, have been investigated. Although these colloidal carriers tend to accumulate selectively in tumour tissues, they are rapidly taken up by the mononuclear phagocytic system. In order to reduce this undesirable uptake by phagocytic cells, long-circulating carriers that consist of surface modified carriers have been developed. Moreover, considerable effort has been directed towards using other types of carriers to improve tumour targeting and to minimize the side effects. One of the approaches is to entrap PS into the lipophilic core of low-density lipoproteins (LDL) without altering their biological properties. The LDL receptor pathway is an important factor in the selective accumulation of PS in tumour tissue owing to the increased number of LDL receptors on the proliferating cell surface. Specific targeting can also be achieved by binding of monoclonal antibodies or specific tumour-seeking molecules to PS or by the coating of PS loaded carriers.
TL;DR: This work gives an analytic description of previous numerical results and generalizes them to arbitrarily high dimensionality and constructs a family of Bell inequalities for bipartite quantum systems of arbitrarily high Dimensionality which are strongly resistant to noise.
Abstract: We develop a novel approach to Bell inequalities based on a constraint that the correlations exhibited by local variable theories must satisfy. This is used to construct a family of Bell inequalities for bipartite quantum systems of arbitrarily high dimensionality which are strongly resistant to noise. In particular, our work gives an analytic description of previous numerical results and generalizes them to arbitrarily high dimensionality.
TL;DR: The large conformational flexibility of HSp90 and a multitude of dynamic co-chaperone complexes contribute to generating functional diversity, and allow Hsp90 to assist a wide range of substrates.
Abstract: Heat-shock protein 90 (Hsp90) is an abundant and highly conserved molecular chaperone that is essential for viability in eukaryotes. Hsp90 fulfills a housekeeping function in contributing to the folding, maintenance of structural integrity and proper regulation of a subset of cytosolic proteins. A remarkable proportion of its substrates are proteins involved in cell cycle control and signal transduction. Hsp90 acts with a cohort of Hsp90 co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. The large conformational flexibility of Hsp90 and a multitude of dynamic co-chaperone complexes contribute to generating functional diversity, and allow Hsp90 to assist a wide range of substrates.
TL;DR: The mammalian circadian timing system is composed of almost as many individual clocks as there are cells, and these countless oscillators have to be synchronized by a central pacemaker to coordinate temporal physiology and behavior.
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TL;DR: In this article, the authors provide a theoretical foundation for rescuing Bagehot's view and derive policy implications about banking regulation (solvency and liquidity ratios) and interventions of the Lender of Last Resort as well as on the disclosure policy of the Central Bank.
Abstract: The classical doctrine of the Lender of Last Resort, elaborated by Thornton (1802) and Bagehot (1873), asserts that the Central Bank should lend to 'illiquid but solvent' banks under certain conditions. Several authors have argued that this view is now obsolete: when interbank markets are efficient, a solvent bank cannot be illiquid. This Paper provides a possible theoretical foundation for rescuing Bagehot's view. Our theory does not rely on the multiplicity of equilibria that arises in classical models of bank runs. We build a model of banks' liquidity crises that possesses a unique Bayesian equilibrium. In this equilibrium, there is a positive probability that a solvent bank cannot find liquidity assistance in the market. We derive policy implications about banking regulation (solvency and liquidity ratios) and interventions of the Lender of Last Resort as well as on the disclosure policy of the Central Bank.
TL;DR: Through numerous examples, it is demonstrated that both techniques allow reduced solvent consumption and shorter extraction times, while the extraction yields of the analytes are equivalent to or even higher than those obtained with conventional methods.
Abstract: In the last 10 years there has been an increased interest in using techniques involving microwave-assisted extraction and pressurised solvent extraction in analytical laboratories This review gives a brief overview of both methods, and reports on their application to the extraction of natural products The influence of parameters such as the nature of the solvent and volume, temperature, time and particle size of the matrix is discussed Through numerous examples, it is demonstrated that both techniques allow reduced solvent consumption and shorter extraction times, while the extraction yields of the analytes are equivalent to or even higher than those obtained with conventional methods
TL;DR: The results show that both H3-K9 acetylation and methylation can occur on independent sets of H3 molecules in pericentric heterochromatin, and identify an RNA- and histone modification–dependent structure that brings methylated H1 protein–binding tails together in a specific configuration required for the accumulation of HP1 proteins in these domains.
Abstract: Post-translational modification of histone tails is thought to modulate higher-order chromatin structure. Combinations of modifications including acetylation, phosphorylation and methylation have been proposed to provide marks recognized by specific proteins. This is exemplified, in both mammalian cells and fission yeast, by transcriptionally silent constitutive pericentric heterochromatin. Such heterochromatin contains histones that are generally hypoacetylated and methylated by Suv39h methyltransferases at lysine 9 of histone H3 (H3-K9). Each of these modification states has been implicated in the maintenance of HP1 protein-binding at pericentric heterochromatin, in transcriptional silencing and in centromere function. In particular, H3-K9 methylation is thought to provide a marking system for the establishment and maintenance of stably repressed regions and heterochromatin subdomains. To address the question of how these two types of modifications, as well as other unidentified parameters, function to maintain pericentric heterochromatin, we used a combination of histone deacetylase inhibitors, RNAse treatments and an antibody raised against methylated branched H3-K9 peptides. Our results show that both H3-K9 acetylation and methylation can occur on independent sets of H3 molecules in pericentric heterochromatin. In addition, we identify an RNA- and histone modification-dependent structure that brings methylated H3-K9 tails together in a specific configuration required for the accumulation of HP1 proteins in these domains.
TL;DR: It is demonstrated that on DCs DC-SIGN is rapidly internalized upon binding of soluble ligand, which points to a novel function of the adhesion receptor DC- SIGN as an efficient DC-specific Ag receptor that can be used as a target to induce viral and antitumor immunity.
Abstract: Dendritic cells (DCs) capture Ags or viruses in peripheral tissue to transport them to lymphoid organs to induce cellular T cell responses. Recently, a DC-specific C-type lectin was identified, DC-specific ICAM-grabbing non-integrin (DC-SIGN), that functions as cell adhesion receptor mediating both DC migration and T cell activation. DC-SIGN also functions as an HIV-1R that captures HIVgp120 and facilitates DC-induced HIV transmission of T cells. Internalization motifs in the cytoplasmic tail of DC-SIGN hint to a function of DC-SIGN as endocytic receptor. In this study we demonstrate that on DCs DC-SIGN is rapidly internalized upon binding of soluble ligand. Mutating a putative internalization motif in the cytoplasmic tail reduces ligand-induced internalization. Detailed analysis using ratio fluorescence imaging and electron microscopy showed that DC-SIGN-ligand complexes are targeted to late endosomes/lysosomes. Moreover, ligands internalized by DC-SIGN are efficiently processed and presented to CD4+ T cells. The distinct pattern of expression of C-type lectins on DCs in situ and their nonoverlapping Ag recognition profile hint to selective functions of these receptors to allow a DC to recognize a wide variety of Ags and to process these to induce T cell activation. These data point to a novel function of the adhesion receptor DC-SIGN as an efficient DC-specific Ag receptor that can be used as a target to induce viral and antitumor immunity.
TL;DR: It is shown that a set of ponds of small size has more species and has a higher conservation value than a single large pond of the same total area, and that large ponds harbour species missing in the smaller ponds.
TL;DR: A review of the cerebral substrates of the central executive component of the working memory model is presented in this article, where it is shown that different executive functions (manipulating and updating of information, dual-task coordination, inhibition and shifting processes) not only recruit various frontal areas but also depend upon posterior (mainly parietal) regions.
TL;DR: In this article, the main characteristics of the solution chemistry of antimony in relation to its behaviour and fate in natural waters are discussed based on a careful and systematic examination of a comprehensive collection of solution equilibrium and environmentally oriented studies, some published more than 100 years ago.
TL;DR: The three regimens studied are very efficacious for emergency contraception and prevent a high proportion of pregnancies if taken within 5 days of unprotected coitus, and most women menstruated within 2 days of the expected date.
TL;DR: In this paper, a simple model capable of exploiting geostationary satellite visible images for the production of site/time-specific global and direct irradiances is presented, which can also exploit operationally available snow cover resource data.
TL;DR: In this paper, the authors compared generalized additive models (GAM) and ecological niche factor analysis (ENFA) models fitted with identical presence data and computer generated "pseudo" absences.
TL;DR: It is postulate that both endogenous and environmental temperature cycles can participate in the synchronization of peripheral clocks in mammals.
TL;DR: In this article, the authors presented a fibre-optical quantum key distribution system based on the plug-and-play set-up, which works at 1550nm and is tested under field conditions using aerial and terrestrial cables and performed key exchange over 67 km between Geneva and Lausanne.
Abstract: We present a fibre-optical quantum key distribution system. It works at 1550 nm and is based on the plug&play set-up. We tested the stability under field conditions using aerial and terrestrial cables and performed a key exchange over 67 km between Geneva and Lausanne.
TL;DR: In this article, a new formulation for the Linke turbidity coefficient with the objective of removing its dependence upon solar geometry is proposed, and two simple clear sky models for global and direct normal irradiance are developed.
TL;DR: The electric field dependence of the domain wall velocity demonstrates that domain wall motion in ferroelectric thin films is a creep process, with the critical exponent mu close to 1.The dimensionality of the films suggests that disorder is at the origin of the observed creep behavior.
Abstract: Ferroelectric switching and nanoscale domain dynamics were investigated using atomic force microscopy on monocrystalline $\mathrm{P}\mathrm{b}\mathrm{(}\mathrm{Z}{\mathrm{r}}_{\mathrm{0.2}}\mathrm{T}{\mathrm{i}}_{\mathrm{0.8}}\mathrm{)}{\mathrm{O}}_{\mathrm{3}}$ thin films. Measurements of domain size versus writing time reveal a two-step domain growth mechanism, in which initial nucleation is followed by radial domain wall motion perpendicular to the polarization direction. The electric field dependence of the domain wall velocity demonstrates that domain wall motion in ferroelectric thin films is a creep process, with the critical exponent $\ensuremath{\mu}$ close to 1. The dimensionality of the films suggests that disorder is at the origin of the observed creep behavior.