Elastoplastic analysis of plane steel frames under dynamic loading

Knowledge of structural behavior is essential for designing lighter constructions without affecting their safety and quality standards. Lack of levels and characteristics of dynamic response, for example, can lead to system failure during repetitive loading application, due to the accumulation of structural damage. Thus, it becomes necessary to use more complex theories, such as nonlinear formulations, avoiding simplifications in the process of analysis/design. Plastic analysis of steel structures enhances several benefits compared to the elastic’s, because one of the most important characteristics of this material, the ductility - ability to withstand large deformations before breaking - is fully considered. This allows for force redistribution after the yielding limit of some structural member’s cross section has been achieved. This property also promotes the absorption of energy, which becomes extremely important in structures subjected to seismic excitation

Monitoring Breast Cancer Response to Neoadjuvant Chemotherapy Using Ultrasound Strain Elastography

© 2019 The Authors Strain elastography was used to monitor response to neoadjuvant chemotherapy (NAC) in 92 patients with biopsy-proven, locally advanced breast cancer. Strain elastography data were collected before, during, and after NAC. Relative changes in tumor strain ratio (SR) were calculated over time, and responder status was classified according to tumor size changes. Statistical analyses determined the significance of changes in SR over time and between response groups. Machine learning techniques, such as a naïve Bayes classifier, were used to evaluate the performance of the SR as a marker for Miller-Payne pathological endpoints. With pathological complete response (pCR) as an endpoint, a significant difference (P < .01) in the SR was observed between response groups as early as 2 weeks into NAC. Naïve Bayes classifiers predicted pCR with a sensitivity of 84%, specificity of 85%, and area under the curve of 81% at the preoperative scan. This study demonstrates that strain elastography may be predictive of NAC response in locally advanced breast cancer as early as 2 weeks into treatment, with high sensitivity and specificity, granting it the potential to be used for active monitoring of tumor response to chemotherapy

Genome sequencing suggests diverse secondary metabolism in coral-associated aquimarina megaterium

We report here the genome sequences of three Aquimarina megaterium strains isolated from the octocoral Euniceila labiata. We reveal a coding potential for versatile carbon metabolism and biosynthesis of natural products belonging to the polyketide, nonribosomal peptide, and terpene compound classes.info:eu-repo/semantics/publishedVersio

The Roseibium album (Labrenzia alba) genome possesses multiple symbiosis factors possibly underpinning host-microbe relationships in the Marine Benthos

Here, we announce the genomes of eight Roseibium album (synonym Labrenzia alba) strains that were obtained from the octocoral Eunicella labiata. Genome annotation revealed multiple symbiosis factors common to all genomes, such as eukaryotic-like repeat protein- and multidrug resistance-encoding genes, which likely underpin symbiotic relationships with marine invertebrate hosts.info:eu-repo/semantics/publishedVersio

Variability of Disk Emission in Pre-Main Sequence and Related Stars IV. Investigating the Structural Changes in the Inner Disk Region of MWC 480

We present five epochs of near IR observations of the protoplanetary disk around MWC 480 (HD31648) obtained with the SpeX spectrograph on NASA's Infrared Telescope Facility (IRTF) between 2007 and 2013, inclusive. Using the measured line fluxes in the Pa beta and Br gamma lines, we found the mass accretion rates to be (1.43 - 2.61)x10^-8 Msun y^-1 and (1.81 - 2.41)x10^-8 Msun y^-1 respectively, but which varied by more than 50% from epoch to epoch. The spectral energy distribution (SED)reveals a variability of about 30% between 1.5 and 10 microns during this same period of time. We investigated the variability using of the continuum emission of the disk in using the Monte-Carlo Radiative Transfer Code (MCRT) HOCHUNK3D. We find that varying the height of the inner rim successfully produces a change in the NIR flux, but lowers the far IR emission to levels below all measured fluxes. Because the star exhibits bipolar flows, we utilized a structure that simulates an inner disk wind to model the variability in the near IR, without producing flux levels in the far IR that are inconsistent with existing data. For this object, variable near IR emission due to such an outflow is more consistent with the data than changing the scale height of the inner rim of the disk.Comment: 19 pages, 14 figure

Differences in the gas and dust distribution in the transitional disk of a sun-like young star, PDS 70

We present ALMA 0.87 mm continuum, HCO+ J=4--3 emission line, and CO J=3--2 emission line data of the disk of material around the young, Sun-like star PDS 70. These data reveal the existence of a possible two component transitional disk system with a radial dust gap of 0."2 +/- 0."05, an azimuthal gap in the HCO+ J=4--3 moment zero map, as well as two bridge-like features in the gas data. Interestingly these features in the gas disk have no analogue in the dust disk making them of particular interest. We modeled the dust disk using the Monte Carlo radiative transfer code HOCHUNK3D (Whitney et al. 2013) using a two disk components. We find that there is a radial gap that extends from 15-60 au in all grain sizes which differs from previous work

Non-peptidic Cruzain Inhibitors with Trypanocidal Activity Discovered by Virtual Screening and in Vitro Assay

A multi-step cascade strategy using integrated ligand-and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K-i) in the low micromolar range (3-60 mu M) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4-80 mu M), yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. in order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR) studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. the IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6 +/- 0.1 mu M, tenfold lower than that obtained for benznidazole, which was taken as positive control. in addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE) of 0.33 kcal mol(-1) atom(-1) (compound Nequimed176) is highlighted as a novel non-peptidic, non-covalent cruzain inhibitor as a trypanocidal agent candidate for optimization.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Sao Carlos, Dept Quim, BR-13560 Sao Carlos, SP, BrazilUniv São Paulo, Inst Quim Sao Carlos, Grp Quim Med IQSC USP, Sao Carlos, SP, BrazilUniv Calif San Francisco, Dept Pathol, Ctr Discovery & Innovat Parasit Dis, San Francisco, CA 94140 USAUniv São Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilFAPESP: 2011/01893-3,CNPq: 301614/2010-5CAPES: 5985/11-0Web of Scienc

Mitochondrial DNA signals of late glacial recolonization of Europe from near Eastern refugia

Human populations, along with those of many other species, are thought to have contracted into a number of refuge areas at the height of the last Ice Age. European populations are believed to be, to a large extent, the descendants of the inhabitants of these refugia, and some extant mtDNA lineages can be traced to refugia in Franco-Cantabria (haplogroups H1, H3, V, and U5b1), the Italian Peninsula (U5b3), and the East European Plain (U4 and U5a). Parts of the Near East, such as the Levant, were also continuously inhabited throughout the Last Glacial Maximum, but unlike western and eastern Europe, no archaeological or genetic evidence for Late Glacial expansions into Europe from the Near East has hitherto been discovered. Here we report, on the basis of an enlarged whole-genome mitochondrial database, that a substantial, perhaps predominant, signal from mitochondrial haplogroups J and T, previously thought to have spread primarily from the Near East into Europe with the Neolithic population, may in fact reflect dispersals during the Late Glacial period, ?19–12 thousand years (ka) ago.<br/

Scalable production of human mesenchymal stromal cell-derived extracellular vesicles under serum-/xeno-free conditions in a microcarrier-based bioreactor culture system

Copyright © 2020 de Almeida Fuzeta, Bernardes, Oliveira, Costa, Fernandes-Platzgummer, Farinha, Rodrigues, Jung, Tseng, Milligan, Lee, Castanho, Gaspar, Cabral and da Silva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Mesenchymal stromal cells (MSC) hold great promise for tissue engineering and cell-based therapies due to their multilineage differentiation potential and intrinsic immunomodulatory and trophic activities. Over the past years, increasing evidence has proposed extracellular vesicles (EVs) as mediators of many of the MSC-associated therapeutic features. EVs have emerged as mediators of intercellular communication, being associated with multiple physiological processes, but also in the pathogenesis of several diseases. EVs are derived from cell membranes, allowing high biocompatibility to target cells, while their small size makes them ideal candidates to cross biological barriers. Despite the promising potential of EVs for therapeutic applications, robust manufacturing processes that would increase the consistency and scalability of EV production are still lacking. In this work, EVs were produced by MSC isolated from different human tissue sources [bone marrow (BM), adipose tissue (AT), and umbilical cord matrix (UCM)]. A serum-/xeno-free microcarrier-based culture system was implemented in a Vertical-WheelTM bioreactor (VWBR), employing a human platelet lysate culture supplement (UltraGROTM-PURE), toward the scalable production of MSC-derived EVs (MSC-EVs). The morphology and structure of the manufactured EVs were assessed by atomic force microscopy, while EV protein markers were successfully identified in EVs by Western blot, and EV surface charge was maintained relatively constant (between −15.5 ± 1.6 mV and −19.4 ± 1.4 mV), as determined by zeta potential measurements. When compared to traditional culture systems under static conditions (T-flasks), the VWBR system allowed the production of EVs at higher concentration (i.e., EV concentration in the conditioned medium) (5.7-fold increase overall) and productivity (i.e., amount of EVs generated per cell) (3-fold increase overall). BM, AT and UCM MSC cultured in the VWBR system yielded an average of 2.8 ± 0.1 × 1011, 3.1 ± 1.3 × 1011, and 4.1 ± 1.7 × 1011 EV particles (n = 3), respectively, in a 60 mL final volume. This bioreactor system also allowed to obtain a more robust MSC-EV production, regarding their purity, compared to static culture. Overall, we demonstrate that this scalable culture system can robustly manufacture EVs from MSC derived from different tissue sources, toward the development of novel therapeutic products.unding received by iBB-Institute for Bioengineering and Biosciences from the Portuguese Foundation for Science and Technology (FCT) (UID/BIO/04565/2020) and through the projects PTDC/EQU-EQU/31651/2017, PTDC/BBB-BQB/1693/2014, and PTDC/BTM-SAL/31057/2017 is acknowledged. Funding received from POR de Lisboa 2020 through the project PRECISE – Accelerating progress toward the new era of precision medicine (Project N. 16394) is also acknowledged. MAF (PD/BD/128328/2017) and FO (PD/BD/135046/2017) acknowledge FCT for the Ph.D. fellowships and DG (SFRH/BPD/109010/2015) for the Post-Doctoral fellowship.info:eu-repo/semantics/publishedVersio