878 research outputs found

    A phase-field approximation of the Willmore flow with volume and area constraints

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    The well-posedness of a phase-field approximation to the Willmore flow with area and volume constraints is established when the functional approximating the area has no critical point satisfying the two constraints. The existence proof relies on the underlying gradient flow structure of the problem: the time discrete approximation is solved by a variational minimization principle. The main difficulty stems from the nonlinearity of the area constraint

    Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-“decoy” strategy

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    MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and subsequent neutralization-we identified a single aminoacid in the extracellular domain of MET-lysine 842-that is critical for MvDN30 binding and engineered the corresponding recombinant decoyMET (K842E). DecoyMET(K842E) retains the ability to bind HGF with high affinity and inhibits HGF-induced MET phosphorylation. In HGF-dependent cellular models, MvDN30 antibody and decoyMET(K842E) used in combination cooperate in restraining invasive growth, and synergize in blocking cancer cell "scattering." The antibody and the decoy unbridle apoptosis of colon cancer stem cells grown in vitro as spheroids. In a preclinical model, built by orthotopic transplantation of a human pancreatic carcinoma in SCID mice engineered to express human HGF, concomitant treatment with antibody and decoy significantly reduces metastatic spread. The data reported indicate that vertical targeting of the MET/HGF axis results in powerful inhibition of ligand-dependent MET activation, providing proof of concept in favor of combined target therapy of MET "expedience.

    Phase field approach to optimal packing problems and related Cheeger clusters

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    In a fixed domain of RN\Bbb{R}^N we study the asymptotic behaviour of optimal clusters associated to α\alpha-Cheeger constants and natural energies like the sum or maximum: we prove that, as the parameter α\alpha converges to the "critical" value (N−1N)+\Big (\frac{N-1}{N}\Big ) _+, optimal Cheeger clusters converge to solutions of different packing problems for balls, depending on the energy under consideration. As well, we propose an efficient phase field approach based on a multiphase Gamma convergence result of Modica-Mortola type, in order to compute α\alpha-Cheeger constants, optimal clusters and, as a consequence of the asymptotic result, optimal packings. Numerical experiments are carried over in two and three space dimensions

    Classifying human motor imagery abilities from heart rate variability analysis: a preliminary study

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    Frontal brain asymmetries as effective parameters to assess the quality of audiovisual stimuli perception in adult and young cochlear implant users

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    How is music perceived by cochlear implant (CI) users? This question arises as "the next step" given the impressive performance obtained by these patients in language perception. Furthermore, how can music perception be evaluated beyond self-report rating, in order to obtain measurable data? To address this question, estimation of the frontal electroencephalographic (EEG) alpha activity imbalance, acquired through a 19-channel EEG cap, appears to be a suitable instrument to measure the approach/withdrawal (AW index) reaction to external stimuli. Specifically, a greater value of AW indicates an increased propensity to stimulus approach, and vice versa a lower one a tendency to withdraw from the stimulus. Additionally, due to prelingually and postlingually deafened pathology acquisition, children and adults, respectively, would probably differ in music perception. The aim of the present study was to investigate children and adult CI users, in unilateral (UCI) and bilateral (BCI) implantation conditions, during three experimental situations of music exposure (normal, distorted and mute). Additionally, a study of functional connectivity patterns within cerebral networks was performed to investigate functioning patterns in different experimental populations. As a general result, congruency among patterns between BCI patients and control (CTRL) subjects was seen, characterised by lowest values for the distorted condition (vs. normal and mute conditions) in the AW index and in the connectivity analysis. Additionally, the normal and distorted conditions were significantly different in CI and CTRL adults, and in CTRL children, but not in CI children. These results suggest a higher capacity of discrimination and approach motivation towards normal music in CTRL and BCI subjects, but not for UCI patients. Therefore, for perception of music CTRL and BCI participants appear more similar than UCI subjects, as estimated by measurable and not self-reported parameters

    A study of methyl formate in astrochemical environments

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    Several complex organic molecules are routinely detected in high abundances towards hot cores and hot corinos. For many of them, their paths of formation in space are uncertain, as gas phase reactions alone seem to be insufficient. In this paper, we investigate a possible solid-phase route of formation for methyl formate (HCOOCH3). We use a chemical model updated with recent results from an experiment where simulated grain surfaces were irradiated with 200 keV protons at 16 K, to simulate the effects of cosmic ray irradiation on grain surfaces. We find that this model may be sufficient to reproduce the observed methyl formate in dark clouds, but not that found in hot cores and corinos.Comment: 6 pages, 2 figures, 2 tables Accepted by MNRA

    Sympatric sibling species: The case of Caloria elegans and Facelina quatrefagesi (Gastropoda: Nudibranchia)

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    The aeolid nudibranch Caloria elegans (Facelinidae) is quite common in the Mediterranean Sea and eastern Atlantic Ocean and is easily recognized by the presence of a typical black spot at the apical portion of its cerata. Facelina quatrefagesi (Facelinidae) was long considered as a synonym of C. elegans until recently, when it was re-evaluated as a valid species based mainly on rhinophore morphology. In order to definitively assess the status of these aeolid taxa, we employed an integrative taxonomy approach using the nuclear H3 and the two mitochondrial cytochrome oxidase subunit I and 16S markers. The molecular analyses clearly showed that, although morphologically closely related to C. elegans, F. quatrefagesi is a valid species

    Une approche simplifiée pour la conception de tranchées d'infiltration

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    Colloque avec actes et comité de lecture. Internationale.International audienc

    Droplet minimizers for the Gates-Lebowitz-Penrose free energy functional

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    We study the structure of the constrained minimizers of the Gates-Lebowitz-Penrose free-energy functional FGLP(m){\mathcal F}_{\rm GLP}(m), non-local functional of a density field m(x)m(x), x∈TLx\in {\mathcal T}_L, a dd-dimensional torus of side length LL. At low temperatures, FGLP{\mathcal F}_{\rm GLP} is not convex, and has two distinct global minimizers, corresponding to two equilibrium states. Here we constrain the average density L^{-d}\int_{{\cal T}_L}m(x)\dd x to be a fixed value nn between the densities in the two equilibrium states, but close to the low density equilibrium value. In this case, a "droplet" of the high density phase may or may not form in a background of the low density phase, depending on the values nn and LL. We determine the critical density for droplet formation, and the nature of the droplet, as a function of nn and LL. The relation between the free energy and the large deviations functional for a particle model with long-range Kac potentials, proven in some cases, and expected to be true in general, then provides information on the structure of typical microscopic configurations of the Gibbs measure when the range of the Kac potential is large enough
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