Stable Constrained Dynamics

International audienceWe present a unification of the two main approaches to simulate deformable solids, namely elasticity and constraints. Elasticity accurately handles soft to moderately stiff objects, but becomes numerically hard as stiffness increases. Constraints efficiently handle high stiffness, but when integrated in time they can suffer from instabilities in the nullspace directions, generating spurious transverse vibrations when pulling hard on thin inextensible objects or articulated rigid bodies. We show that geometric stiffness, the tensor encoding the change of force directions (as opposed to intensities) in response to a change of positions, is the missing piece between the two approaches. This previously neglected stiffness term is easy to implement and dramatically improves the stability of inextensible objects and articulated chains, without adding artificial bending forces. This allows time step increases up to several orders of magnitude using standard linear solvers

Why do results conflict regarding the prognostic value of the methylation status in colon cancers? the role of the preservation method

<p>Abstract</p> <p>Background</p> <p>In colorectal carcinoma, extensive gene promoter hypermethylation is called the CpG island methylator phenotype (CIMP). Explaining why studies on CIMP and survival yield conflicting results is essential. Most experiments to measure DNA methylation rely on the sodium bisulfite conversion of unmethylated cytosines into uracils. No study has evaluated the performance of bisulfite conversion and methylation levels from matched cryo-preserved and Formalin-Fixed Paraffin Embedded (FFPE) samples using pyrosequencing.</p> <p>Methods</p> <p>Couples of matched cryo-preserved and FFPE samples from 40 colon adenocarcinomas were analyzed. Rates of bisulfite conversion and levels of methylation of <it>LINE-1, MLH1 </it>and <it>MGMT </it>markers were measured.</p> <p>Results</p> <p>For the reproducibility of bisulfite conversion, the mean of bisulfite-to-bisulfite standard deviation (SD) was 1.3%. The mean of run-to-run SD of PCR/pyrosequencing was 0.9%. Of the 40 DNA couples, only 67.5%, 55.0%, and 57.5% of FFPE DNA were interpretable for <it>LINE-1, MLH1</it>, and <it>MGMT </it>markers, respectively, after the first analysis. On frozen samples the proportion of well converted samples was 95.0%, 97.4% and 87.2% respectively. For DNA showing a total bisulfite conversion, 8 couples (27.6%) for <it>LINE-1</it>, 4 couples (15.4%) for <it>MLH1 </it>and 8 couples (25.8%) for <it>MGMT </it>displayed significant differences in methylation levels.</p> <p>Conclusions</p> <p>Frozen samples gave reproducible results for bisulfite conversion and reliable methylation levels. FFPE samples gave unsatisfactory and non reproducible bisulfite conversions leading to random results for methylation levels. The use of FFPE collections to assess DNA methylation by bisulfite methods must not be recommended. This can partly explain the conflicting results on the prognosis of CIMP colon cancers.</p

Seamless Adaptivity of Elastic Models

International audienceA new adaptive model for viscoelastic solids is presented. Unlike previous approaches, it allows seamless transitions, and simplifications in deformed states. The deformation field is generated by a set of physically animated frames. Starting from a fine set of frames and mechanical energy integration points, the model can be coarsened by attaching frames to others, and merging integration points. Since frames can be attached in arbitrary relative positions, simplifications can occur seamlessly in deformed states, without returning to the original shape, which can be recovered later after refinement. We propose a new class of velocity-based simplification criterion based on relative velocities. Integration points can be merged to reduce the computation time even more, and we show how to maintain constant elastic forces through the levels of detail. This meshless adaptivity allows significant improvements of computation time

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.Published versionThe authors thank the UK MS Society for financial support (grant number: C008-16.1). DRO was funded by an MRC Clinician Scientist Award (MR/N008219/1). P.M.M. acknowledges generous support from Edmond J Safra Foundation and Lily Safra, the NIHR Senior Investigator programme and the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. P.M.M. and D.R.O. thank the Imperial College Healthcare Trust-NIHR Biomedical Research Centre for infrastructure support and the Medical Research Council for support of TSPO studies (MR/N016343/1). E.A. was supported by the ALS Stichting (grant “The Dutch ALS Tissue Bank”). P.M. and B.B.T. are funded by the Swiss National Science Foundation (projects 320030_184713 and 310030_212322, respectively). S.T. was supported by an “Early Postdoc.Mobility” scholarship (P2GEP3_191446) from the Swiss National Science Foundation, a “Clinical Medicine Plus” scholarship from the Prof Dr. Max Cloëtta Foundation (Zurich, Switzerland), from the Jean et Madeleine Vachoux Foundation (Geneva, Switzerland) and from the University Hospitals of Geneva. This work was funded by NIH grants U01AG061356 (De Jager/Bennett), RF1AG057473 (De Jager/Bennett), and U01AG046152 (De Jager/Bennett) as part of the AMP-AD consortium, as well as NIH grants R01AG066831 (Menon) and U01AG072572 (De Jager/St George-Hyslop)

Role of clock genes in the decodage of the photoperiod by the suprachiasmatic nuclei and the pars tuberalis in mammals

Les noyaux suprachiasmatiques (SCN) des mammifères sont le siège de l'horloge circadienne. L'objectif de la thèse a été de mettre en évidence que les SCN jouent un rôle dans les rythmes saisonniers et de déterminer comment ces signaux sont décodés par la Pars tuberalis (PT). Dans les SCN, nous montrons que l'expression de gènes (horloges et de sortie de l'horloge) dépend de la photopériode. La chronologie de ces modifications montre que les SCN intègrent le changement de photopériode, et qu ils construisent des messages saisonniers. De plus, le gène Clock semble particulièrement important dans ce fonctionnement saisonnier, y compris au cours de la "photopériode réfractaire". Dans la PT, nous montrons que l'expression des gènes horloges dépend de la photopériode sous le contrôle de la mélatonine qui active l'expression de Cry1 et inhibe celle des autres gènes horloges. A court terme, il apparaît, sauf pour Cry1, que la mélatonine n est pas nécessaire à l'expression des gènes horloges.Physiological and behavioral rhythms are driven by the principal circadian pacemaker located in the SCN (suprachiasmatic nuclei). We tried to demonstrated that SCN play a role in the appearance of the seasonal rhythms and to determine how these messages are decoded in the Pars tuberalis (PT). In the SCN, the genes (clock and clock-controlled) expression depend of the photoperiod. The chronology of the modifications show that SCN integrate the photoperiod and construct seasonal messages. Moreover, the gene Clock seems to be particularly important in this functioning, and also during the "refractory state". In the PT, we show that the clock genes expression depend of the photoperiod under the control of the melatonin which increase the Cry1 expression and inhibit the other genes. In short-term, it seems that, expect for Cry1, melatonin is not necessary for the gene expressions

Neuroimaging and biological role of TSPO in brain disorders

In the last decade, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in vivo imaging has attempted to demonstrate the presence of neuroinflammatory reactions by detecting the 18 kDa translocator protein (TSPO) in many diseases of the central nervous system. Of these diseases, Alzheimer's disease has been the most widely studied with more than forty pre-clinical and clinical studies. Thus, it is now more or less accepted that TSPO is upregulated in Alzheimer's disease. However, studies differ as to the cerebral location of the variations, the timecourse of the appearance of TSPO and the cells responsible for this increase. In the case of schizophrenia, while studies remain more contradictory, it seems that TSPO shows decreases in expression instead. This review focuses on the use of TSPO as a biomarker of neuroinflammation in psychiatric disorders, on the cellular origin of the variations in its expression, on its possible biological/pathological roles and, finally, on its links with other neurochemical actors of Alzheimer's pathology, b-amyloid and neurofibrillary tangles

Role of clock genes in the decodage of the photoperiod by the suprachiasmatic nuclei and the pars tuberalis in mammals

Les noyaux suprachiasmatiques (SCN) des mammifères sont le siège de l'horloge circadienne. L'objectif de la thèse a été de mettre en évidence que les SCN jouent un rôle dans les rythmes saisonniers et de déterminer comment ces signaux sont décodés par laPhysiological and behavioral rhythms are driven by the principal circadian pacemaker located in the SCN (suprachiasmatic nuclei). We tried to demonstrated that SCN play a role in the appearance of the seasonal rhythms and to determine how these messages

Rôle des gènes horloges dans la traduction biologique de la photopériode par les Noyaux Suprachiasmatiques et la Pars tuberalis des mammifères

Les noyaux suprachiasmatiques (SCN) des mammifères sont le siège de l’horloge circadienne. L’objectif de la thèse a été de mettre en évidence que les SCN jouent un rôle dans les rythmes saisonniers et de déterminer comment ces signaux sont décodés par la Pars tuberalis (PT). Dans les SCN, nous montrons que l’expression de gènes (horloges et de sortie de l’horloge) dépend de la photopériode. La chronologie de ces modifications montre que les SCN intègrent le changement de photopériode, et qu’ils construisent des messages saisonniers. De plus, le gène Clock semble particulièrement important dans ce fonctionnement saisonnier, y compris au cours de la "photopériode réfractaire". Dans la PT, nous montrons que l’expression des gènes horloges dépend de la photopériode sous le contrôle de la mélatonine qui active l’expression de Cry1 et inhibe celle des autres gènes horloges. A court terme, il apparaît, sauf pour Cry1, que la mélatonine n’est pas nécessaire à l’expression des gènes horloges.Physiological and behavioral rhythms are driven by the principal circadian pacemaker located in the SCN (suprachiasmatic nuclei). We tried to demonstrated that SCN play a role in the appearance of the seasonal rhythms and to determine how these messages are decoded in the Pars tuberalis (PT). In the SCN, the genes (clock and clock-controlled) expression depend of the photoperiod. The chronology of the modifications show that SCN integrate the photoperiod and construct seasonal messages. Moreover, the gene Clock seems to be particularly important in this functioning, and also during the "refractory state". In the PT, we show that the clock genes expression depend of the photoperiod under the control of the melatonin which increase the Cry1 expression and inhibit the other genes. In short-term, it seems that, expect for Cry1, melatonin is not necessary for the gene expressions