Continuum limit of amorphous elastic bodies (III): Three dimensional systems

Extending recent numerical studies on two dimensional amorphous bodies, we characterize the approach of elastic continuum limit in three dimensional (weakly polydisperse) Lennard-Jones systems. While performing a systematic finite-size analysis (for two different quench protocols) we investigate the non-affine displacement field under external strain, the linear response to an external delta force and the low-frequency harmonic eigenmodes and their density distribution. Qualitatively similar behavior is found as in two dimensions. We demonstrate that the classical elasticity description breaks down below an intermediate length scale $\xi$, which in our system is approximately 23 molecular sizes. This length characterizes the correlations of the non-affine displacement field, the self-averaging of external noise with distance from the source and gives the lower wave length bound for the applicability of the classical eigenfrequency calculations. We trace back the "Boson-peak" of the density of eigenfrequencies (obtained from the velocity auto-correlation function) to the inhomogeneities on wave lengths smaller than $\xi$.Comment: 27 pages, 11 figures, submitted to Phys. Rev.

Lagrangian Floer superpotentials and crepant resolutions for toric orbifolds

We investigate the relationship between the Lagrangian Floer superpotentials for a toric orbifold and its toric crepant resolutions. More specifically, we study an open string version of the crepant resolution conjecture (CRC) which states that the Lagrangian Floer superpotential of a Gorenstein toric orbifold $\mathcal{X}$ and that of its toric crepant resolution $Y$ coincide after analytic continuation of quantum parameters and a change of variables. Relating this conjecture with the closed CRC, we find that the change of variable formula which appears in closed CRC can be explained by relations between open (orbifold) Gromov-Witten invariants. We also discover a geometric explanation (in terms of virtual counting of stable orbi-discs) for the specialization of quantum parameters to roots of unity which appears in Y. Ruan's original CRC ["The cohomology ring of crepant resolutions of orbifolds", Gromov-Witten theory of spin curves and orbifolds, 117-126, Contemp. Math., 403, Amer. Math. Soc., Providence, RI, 2006]. We prove the open CRC for the weighted projective spaces $\mathcal{X}=\mathbb{P}(1,\ldots,1,n)$ using an equality between open and closed orbifold Gromov-Witten invariants. Along the way, we also prove an open mirror theorem for these toric orbifolds.Comment: 48 pages, 1 figure; v2: references added and updated, final version, to appear in CM

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes

Mutations in OPA1, a dynamin-related GTPase involved in mitochondrial fusion, cristae organization and control of apoptosis, have been linked to non-syndromic optic neuropathy transmitted as an autosomal-dominant trait (DOA). We here report on eight patients from six independent families showing that mutations in the OPA1 gene can also be responsible for a syndromic form of DOA associated with sensorineural deafness, ataxia, axonal sensory-motor polyneuropathy, chronic progressive external ophthalmoplegia and mitochondrial myopathy with cytochrome c oxidase negative and Ragged Red Fibres. Most remarkably, we demonstrate that these patients all harboured multiple deletions of mitochondrial DNA (mtDNA) in their skeletal muscle, thus revealing an unrecognized role of the OPA1 protein in mtDNA stability. The five OPA1 mutations associated with these DOA ‘plus’ phenotypes were all mis-sense point mutations affecting highly conserved amino acid positions and the nuclear genes previously known to induce mtDNA multiple deletions such as POLG1, PEO1 (Twinkle) and SLC25A4 (ANT1) were ruled out. Our results show that certain OPA1 mutations exert a dominant negative effect responsible for multi-systemic disease, closely related to classical mitochondrial cytopathies, by a mechanism involving mtDNA instability

Measurement of the cosmogenic activation of germanium detectors in EDELWEISS-III

International audienceWe present a measurement of the cosmogenic activation in the germanium cryogenic detectors of the EDELWEISS III direct dark matter search experiment. The decay rates measured in detectors with different exposures to cosmic rays above ground are converted into production rates of different isotopes. The measured production rates in units of nuclei/kg/day are 82 $\pm$ 21 for $^3$H, 2.8 $\pm$ 0.6 for $^{49}$V, 4.6 $\pm$ 0.7 for $^{55}$Fe, and 106 $\pm$ 13 for $^{65}$Zn. These results are the most accurate for these isotopes. A lower limit on the production rate of $^{68}$Ge of 74 nuclei/kg/day is also presented. They are compared to model predictions present in literature and to estimates calculated with the ACTIVIA code

Signals induced by charge-trapping in EDELWEISS FID detectors: Analytical modeling and applications

The EDELWEISS-III direct dark matter search experiment uses cryogenic HP-Ge detectors Fully covered with Inter-Digitized electrodes (FID). They are operated at low fields (< 1 V/cm), and as a consequence charge-carrier trapping significantly affects both the ionization and heat energy measurements. This paper describes an analytical model of the signals induced by trapped charges in FID detectors based on the Shockley-Ramo theorem. It is used to demonstrate that veto electrodes, initially designed for the sole purpose of surface event rejection, can be used to provide a sensitivity to the depth of the energy deposits, characterize the trapping in the crystals, perform heat and ionization energy corrections and improve the ionization baseline resolutions. These procedures are applied successfully to actual data

Improved EDELWEISS-III sensitivity for low-mass WIMPs using a profile likelihood approach

We report on a dark matter search for a Weakly Interacting Massive Particle (WIMP) in the mass range mχ∈[4,30]GeV/c2 with the EDELWEISS-III experiment. A 2D profile likelihood analysis is performed on data from eight selected detectors with the lowest energy thresholds leading to a combined fiducial exposure of 496 kg-days. External backgrounds from γ- and β-radiation, recoils from 206Pb and neutrons as well as detector intrinsic backgrounds were modelled from data outside the region of interest and constrained in the analysis. The basic data selection and most of the background models are the same as those used in a previously published analysis based on boosted decision trees (BDT) [1]. For the likelihood approach applied in the analysis presented here, a larger signal efficiency and a subtraction of the expected background lead to a higher sensitivity, especially for the lowest WIMP masses probed. No statistically significant signal was found and upper limits on the spin-independent WIMP-nucleon scattering cross section can be set with a hypothesis test based on the profile likelihood test statistics. The 90 % C.L. exclusion limit set for WIMPs with mχ=4GeV/c2 is 1.6×10-39cm2, which is an improvement of a factor of seven with respect to the BDT-based analysis. For WIMP masses above 15GeV/c2 the exclusion limits found with both analyses are in good agreement

TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy

Recent studies have suggested that activation of the EGFR pathway leads to malignant transformation only if the p53 protein is inactivated. Therefore, we evaluated the impact of TP53 mutations on cetuximab-based chemotherapy (CT) sensitivity in combination with KRAS mutations that have been associated with cetuximab resistance. KRAS and TP53 status were assessed in tumours from 64 metastatic colorectal cancer patients treated with cetuximab-based CT and correlated to clinical response using the Fisher's exact test. Times to progression (TTPs) according to gene status were calculated using the Kaplan–Meier method and compared with log-rank test. TP53 mutations were found in 41 patients and were significantly associated with controlled disease (CD), as defined as complete response, partial response or stable disease (P=0.037) and higher TTP (20 vs 12 weeks, P=0.004). Remarkably, in the subgroup of 46 patients without KRAS mutation, but not in patients with KRAS mutation, TP53 mutations were also associated with CD (P=0.008) and higher TTP (24 vs 12 weeks, P=0.0007). This study suggests that TP53 mutations are predictive of cetuximab sensitivity, particularly in patients without KRAS mutation, and that TP53 genotyping could have a clinical interest to select patients who should benefit from cetuximab-based CT