Shannon Wavelet Entropy and Acoustic Emission Applied to Assess Damage in Concrete in Dynamical Tests

Shannon wavelet entropy (SWE), a powerful mathematical tool for transient signal analysis, is applied to acoustic emission signals originated in crack like damages. In previous work, the complex Morlet Continuous Wavelet Transform (CWT) was applied to acoustic emission (AE) signals from dynamic tests conducted on a reinforced concrete slab with a shaking table. Comparison of the evolution of the scale position of maximum values of CWT coefficients and the histories of response acceleration obtained in different seismic simulations allowed us to identify the frequency band corresponding to the fracture of concrete, which is the main failure mechanism. In the present work, the same frequency band, assigned to fracture, was considered. The discrete dyadic wavelet transform (DDWT), a faster transform algorithm, is first used as a filter to obtain the coefficients in the desired frequency band, and then SWE is calculated. SWE is extracted from each AE hit, which allows us to obtain the SWE evolution overthe test duration and connect sharp transitions of entropy values with the occurrence of dangerous macrocracks.Publicado en: Mecánica Computacional vol. XXXV no.44Facultad de Ingenierí

Light, medium-weight or heavy? The nature of the first supermassive black hole seeds

Observations of hyper-luminous quasars at $z>6$ reveal the rapid growth of supermassive black holes (SMBHs $>10^9 \rm M_{\odot}$) whose origin is still difficult to explain. Their progenitors may have formed as remnants of massive, metal free stars (light seeds), via stellar collisions (medium-weight seeds) and/or massive gas clouds direct collapse (heavy seeds). In this work we investigate for the first time the relative role of these three seed populations in the formation of $z>6$ SMBHs within an Eddington-limited gas accretion scenario. To this aim, we implement in our semi-analytical data-constrained model a statistical description of the spatial fluctuations of Lyman-Werner (LW) photo-dissociating radiation and of metal/dust enrichment. This allows us to set the physical conditions for BH seeds formation, exploring their relative birth rate in a highly biased region of the Universe at $z>6$. We find that the inclusion of medium-weight seeds does not qualitatively change the growth history of the first SMBHs: although less massive seeds ($<10^3 \rm M_\odot$) form at a higher rate, the mass growth of a $\sim 10^9 \rm M_\odot$ SMBH at $z<15$ is driven by efficient gas accretion (at a sub-Eddington rate) onto its heavy progenitors ($10^5 \rm M_\odot$). This conclusion holds independently of the critical level of LW radiation and even when medium-weight seeds are allowed to form in higher metallicity galaxies, via the so-called super-competitive accretion scenario. Our study suggests that the genealogy of $z \sim 6$ SMBHs is characterized by a rich variety of BH progenitors, which represent only a small fraction ($< 10 - 20\%$) of all the BHs that seed galaxies at $z > 15$.Comment: (21 pages, 18 figures, 2 tables. Accepted for publication in MNRAS

Role of extracellular microvesicles in celiac disease as potential pathogenetic agents and biomarkers of intestinal inflammation

BACKGROUND AND AIM: Celiac Disease (CD) is a chronic intestinal disease caused by the ingestion of gluten. Microvesicles (MVs) belong to a heterogeneous population, released by cells both in homeostasis and pathological conditions. MVs can be considered mediators of inflammation and potential biomarkers. The aim of this study is: 1) to evaluate the possible role of MVs in the propagation of inflammation in CD, using MVs purified by supernatant of duodenal biopsies from CD patients; 2) to identify potential biomarkers by proteomic analysis of pasma-derived MVs from CD patients. MATERIAL AND METHODS: MVs were isolated by molecular exclusion chromatography and ultracentrifugation respectively from plasma and culture supernatant of duodenal biopsies of 10 active CD, 5 remission CD and 6 controls. Proteomic analysis of plasma-derived MVs was performed by mass spectrometry. The possible effects of duodenal-derived MVs on confluent Caco-2 cells were evaluated by measuring Transepithelial Electrical Resistance (TEER) and analyzing the expression of actin, tissue transglutaminase (TG2) and Zonula Occludens-1 (ZO-1). The dosage of IL-8 in the Caco-2 culture supernatant was carried out by ELISA test. The statistical analysis of the data obtained was performed using the Student's t-test. RESULTS: The proteomic analysis of circulating MVs showed 8 proteins from desmosome and cytoskeleton (desmoglein-1 and gamma-enteric actin) associated with the active phase of the disease. Caco-2 cells, treated with the MVs purified from the duodenal biopsies of active CD patients showed: 1) rearrangement of actin filaments; 2) increased expression of TG2; 3) decreased expression of the ZO-1 protein, although an alteration of intestinal permeability was not observed. The analysis of Caco-2 cell supernatants showed a statistically significant increase in IL-8 (p &lt;0.05), in the presence of MVs isolated from biopsies of active CD patients, compared to remission CD patients and controls. CONCLUSIONS: MVs isolated from plasma of active CD patients could represent potential diagnostic and prognostic biomarkers. Although they don’t induce changes in intestinal permeability, MVs could contribute to inflammatory cascade increasing IL-8 production

Loss of Primary Cilia Potentiates BRAF/MAPK Pathway Activation in Rhabdoid Colorectal Carcinoma: A Series of 21 Cases Showing Ciliary Rootlet CoiledCoil (CROCC) Alterations

A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the SMARCB1 and Ciliary Rootlet Coiled-Coil (CROCC). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing. Mismatch repair-deficient phenotypes were identified in 60% of RCTs. Similarly, a large proportion of cancers exhibited the combined marker phenotype (CK7-/CK20-/CDX2-) not common to classical adenocarcinoma variants. More than 70% of cases displayed aberrant activation of the mitogen-activated protein kinase (MAPK) pathway with mutations prevalently in BRAF V600E. SMARCB1/INI1 expression was normal in a large majority of lesions. In contrast, ciliogenic markers including CROCC and γ-tubulin were globally altered in tumors. Notably, CROCC and γ-tubulin were observed to colocalize in large cilia found on cancer tissues but not in normal controls. Taken together, our findings indicate that primary ciliogenesis and MAPK pathway activation contribute to the aggressiveness of RCTs and, therefore, may constitute a novel therapeutic target

N -Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT 2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues

A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at serotonin receptors showed that most of the compounds had the highest affinity at the 5-HT2 family receptors. Substitution at the para position of the benzyl group resulted in reduced affinity, whereas substitution in either the ortho or the meta position enhanced affinity. In general, introduction of a large lipophilic group improved affinity, whereas functional activity often followed the opposite trend. Tests of the compounds for functional activity utilized intracellular Ca2+ mobilization. Function was measured at the human 5-HT2A, 5-HT2B, and 5-HT2C receptors, as well as at the rat 5-HT2A and 5-HT2C receptors. There was no general correlation between affinity and function. Several of the tryptamine congeners were very potent functionally (EC50 values from 7.6 to 63 nM), but most were partial agonists. Tests in the mouse head twitch assay revealed that many of the compounds induced the head twitch and that there was a significant correlation between this behavior and functional potency at the rat 5-HT2A receptor

Rational Drug Design Leading to the Identification of a Potent 5-HT 2C Agonist Lacking 5-HT 2B Activity

The 5-HT2C receptor is an attractive drug target in the quest for new therapeutics to treat a variety of human disorders. We have previously undertaken a structural optimization campaign that has led to some potent and moderately selective 5-HT2C receptor agonists. After expanding our structure–function library, we were able to combine our data sets so as to allow the design of compounds of improved selectivity and potency. We disclose herein the structural optimization of our previously reported 5-HT2B/5-HT2C agonists, which has led to the identification of a highly selective 5-HT2C agonist, (+)-trans-[2-(2-cyclopropylmethoxyphenyl)cyclopropyl]methylamine hydrochloride, with an EC50 of 55 nM and no detectable agonism at the 5-HT2B receptor