A multiscale XFEM approach to investigate the fracture behavior of bio-inspired composite materials

In the setting of emerging approaches for material design, we investigate the use of the extended finite element method (XFEM) to predict the behavior of a newly designed bone-inspired fiber-reinforced composite and to elucidate the role of the characteristic microstructural features and interfaces on the overall fracture behavior. The outcome of the simulations, showing a good agreement with the experimental results, reveals the fundamental role played by the heterogeneous microstructure in altering the stress field, reducing the stress concentration at the crack tip, and the crucial role of the interface region (i.e. cement line) in fostering the activation of characteristic toughening mechanisms, thus increasing the overall flaw tolerance of the composite

BRAF AND MAPK PATHWAY MOLECULES FOR TARGETED THERAPY OF MALIGNANT MELANOMA

The clinical activity of the BRAF inhibitor PLX4032 (vemurafenib) in patients with BRAFV600E mutant melanoma is limited primarily by the development of resistance leading to tumor progression. Strategies to overcome primary and acquired resistance are required. In a panel of 27 genetically characterized patient-derived melanoma cell lines the sensitivity to PLX4032 was dependent on BRAFV600E and independent from other gene alterations that commonly occur in melanoma, such as CDKN2A, and mutations of TP53, PTEN loss, and BRAF and MITF gene amplification. To investigate the molecular basis underlying acquired resistance to BRAF inhibitor, PLX4032-resistant cells were derived from a high sensitive BRAFV600E melanoma cell line, and used as a model. The resistant variant line showed increased AKT and ERK phosphorylation and enhanced IGF-1R/PI3K signaling. Combined treatment with PLX4032 plus PI3K inhibitors resulted in significant cell growth inhibition by decreasing pAKT and pERK signaling. To explore molecular mechanisms underlying primary resistance two melanoma cell lines lacking sensitivity to PLX4032 were used as models. Resistance to PLX4032 was maintained after CRAF down-regulation by siRNA, indicating that CRAF is not involved in the activation of ERK in the resistant cell lines. Treatment with the MEK inhibitor UO126 inhibited cell growth and decreased ERK phosphorylation indicating alternative activation of MEK-ERK signaling. Genetic characterization by MLPA and analysis of pTyr signaling by MALDI-TOF mass spectrometry revealed the activation of MET and SRC signaling, associated with the amplification of MET and of CTNNB1 and CCND1 genes, respectively. Testing of co-inhibition of the MET, SRC and MAPK signaling pathways by the combined treatment with the MET inhibitor, SU11274 or the SRC inhibitor, BMS-354825 plus PLX4032 resulted in a significant inhibitory effect on melanoma cell proliferation, survival, migration and invasive capacity. These results support combinatorial approaches targeting MAPK pathway at different nodes and intercepting parallel signal transduction pathways as a strategy to override resistance to BRAF inhibitors

Mucopexy-Recto Anal Lifting (MuRAL) in managing obstructed defecation syndrome associated with prolapsed hemorrhoids and rectocele : preliminary results

Purpose: Treatment of rectocele associated with prolapsed hemorrhoids is a debated topic. Transanal stapling achieved good midterm results in patients with symptoms of obstructed defecation, nevertheless a number of severe complications have been reported. The aim of this study was to evaluate the safety and efficacy of a new endorectal manual technique in patients with obstructed defecation due to the combination of muco-hemorrhoidal prolapse and rectocele. Methods: Patients enrolled after preoperative obstructed defecation syndrome (ODS) score, defecography and anoscopy were submitted to the novel Mucopexy-Recto Anal Lifting (MuRAL) combined with a modified Block procedure, and followed up by independent observers with digital exploration 3 weeks postoperatively, and digital exploration plus anoscopy at 3, 6, and 12 months. Operative time, hospital stay, numerating rating scale (NRS), ODS, satisfaction scores, and recurrence rate were recorded. Results: Mean operative time was 35.7 minutes. Fifty-six patients completed 1-year follow-up: 7.1% had acute urinary retention, NRS score was < 3 from the third postoperative day, mean time of daily activity resumption was 12 days, none had persistent fecal urgency, 82% declared excellent/good satisfaction score, significant improvement of 6- and 12-month ODS score, no recurrence of rectocele, and 7.1% recurrence of prolapsed hemorrhoids were observed. Conclusion: MuRAL associated with modified Block technique gave no severe complications and resulted in a safe and effective approach to symptomatic rectocele associated with muco-rectal prolapse. Further randomized studies, larger series, and longer follow-up are needed. [Ann Surg Treat Res 2020;98(5):277-282

Design of an ankle prosthesis for swimming and walking

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Integral field spectroscopy with SINFONI of VVDS galaxies. II. The mass-metallicity relation at 1.2 < z < 1.6

This work aims to provide a first insight into the mass-metallicity (MZ) relation of star-forming galaxies at redshift z~1.4. To reach this goal, we present a first set of nine VVDS galaxies observed with the NIR integral-field spectrograph SINFONI on the VLT. Oxygen abundances are derived from empirical indicators based on the ratio between strong nebular emission-lines (Halpha, [NII]6584 and [SII]6717,6731). Stellar masses are deduced from SED fitting with Charlot & Bruzual (2007) population synthesis models, and star formation rates are derived from [OII]3727 and Halpha emission-line luminosities. We find a typical shift of 0.2-0.4 dex towards lower metallicities for the z~1.4 galaxies, compared to the MZ-relation in the local universe as derived from SDSS data. However, this small sample of eight galaxies does not show any clear correlation between stellar mass and metallicity, unlike other larger samples at different redshift (z~0, z~0.7, and z~2). Indeed, our galaxies lie just under the relation at z~2 and show a small trend for more massive galaxies to be more metallic (~0.1 logarithmic slope). There are two possible explanations to account for these observations. First, the most massive galaxies present higher specific star formation rates when compared to the global VVDS sample which could explain the particularly low metallicity of these galaxies as already shown in the SDSS sample. Second, inflow of metal-poor gas due to tidal interactions could also explain the low metallicity of these galaxies as two of these three galaxies show clear signatures of merging in their velocity fields. Finally, we find that the metallicity of 4 galaxies is lower by ~0.2 to 0.4 dex if we take into account the N/O abundance ratio in their metallicity estimate.Comment: 7 pages, 4 figures, accepted in A&A Comments: Comments: more accurate results with better stellar mass estimate

Microbial assisted phytodepuration for water reclamation: Environmental benefits and threats

Climate changes push for water reuse as a priority to counteract water scarcity and minimize water footprint especially in agriculture, one of the highest water consuming human activities. Phytodepuration is indicated as a promising technology for water reclamation, also in the light of its economic and ecological sustainability, and the use of specific bacterial inocula for microbial assisted phytodepuration has been proposed as a further advance for its implementation. Here we provided an overview on the selection and use of plant growth promoting bacteria in Constructed Wetland (CW) systems, showing their advantages in terms of plant growth support and pollutant degradation abilities. Moreover, CWs are also proposed for the removal of emerging organic pollutants like antibiotics from urban wastewaters. We focused on this issue, still debated in the literature, revealing the necessity to deepen the knowledge on the antibiotic resistance spread into the environment in relation to treated wastewater release and reuse. In addition, given the presence in the plant system of microhabitats (e.g. rhizosphere) that are hot spot for Horizontal Gene Transfer, we highlighted the importance of gene exchange to understand if these events can promote the diffusion of antibiotic resistance genes and antibiotic resistant bacteria, possibly entering in the food production chain when treated wastewater is used for irrigation. Ideally, this new knowledge will lead to improve the design of phytodepuration systems to maximize the quality and safety of the treated effluents in compliance with the 'One Health' concept

Dust and dark Gamma-Ray Bursts: mutual implications

In a cosmological context dust has been always poorly understood. That is true also for the statistic of GRBs so that we started a program to understand its role both in relation to GRBs and in function of z. This paper presents a composite model in this direction. The model considers a rather generic distribution of dust in a spiral galaxy and considers the effect of changing some of the parameters characterizing the dust grains, size in particular. We first simulated 500 GRBs distributed as the host galaxy mass distribution, using as model the Milky Way. If we consider dust with the same properties as that we observe in the Milky Way, we find that due to absorption we miss about 10% of the afterglows assuming we observe the event within about 1 hour or even within 100s. In our second set of simulations we placed GRBs randomly inside giants molecular clouds, considering different kinds of dust inside and outside the host cloud and the effect of dust sublimation caused by the GRB inside the clouds. In this case absorption is mainly due to the host cloud and the physical properties of dust play a strong role. Computations from this model agree with the hypothesis of host galaxies with extinction curve similar to that of the Small Magellanic Cloud, whereas the host cloud could be also characterized by dust with larger grains. To confirm our findings we need a set of homogeneous infrared observations. The use of coming dedicated infrared telescopes, like REM, will provide a wealth of cases of new afterglow observations.Comment: 16 pages, 8 figures, accepted by A&

New light on gamma-ray burst host galaxies with Herschel

Until recently, dust emission has been detected in very few host galaxies of gamma-ray bursts (GRBHs). With Herschel, we have now observed 17 GRBHs up to redshift z~3 and detected seven of them at infrared (IR) wavelengths. This relatively high detection rate (41%) may be due to the composition of our sample which at a median redshift of 1.1 is dominated by the hosts of dark GRBs. Although the numbers are small, statistics suggest that dark GRBs are more likely to be detected in the IR than their optically-bright counterparts. Combining our IR data with optical, near-infrared, and radio data from our own datasets and from the literature, we have constructed spectral energy distributions (SEDs) which span up to 6 orders of magnitude in wavelength. By fitting the SEDs, we have obtained stellar masses, dust masses, star-formation rate (SFR), and extinctions for our sample galaxies. We find that GRBHs are galaxies that tend to have a high specfic SFR (sSFR), and like other star-forming galaxies, their ratios of dust-to-stellar mass are well correlated with sSFR. We incorporate our Herschel sample into a larger compilation of GRBHs, and compare this combined sample to SFR-weighted median stellar masses of the widest, deepest galaxy survey to date. This is done in order to establish whether or not GRBs can be used as an unbiased tracer of cosmic comoving SFR density (SFRD) in the universe. In contrast with previous results, this comparison shows that GRBHs are medium-sized galaxies with relatively high sSFRs; stellar masses and sSFRs of GRBHs as a function of redshift are similar to what is expected for star-forming galaxy populations at similar redshifts. We conclude that there is no strong evidence that GRBs are biased tracers of SFRD; thus they should be able to reliably probe the SFRD to early epochs.Comment: 18 pages, 9 figures, accepted for publication in A&A. Revised to include Fig. 6, mistakenly omitted in origina