Numerical explicit analysis of hole flanging by single-stage incremental forming

The use of Single-Point Incremental Forming (SPIF) technology in hole flanging operations using multi-stages strategies have been widely studied in the last few years. However, these strategies are very time-consuming, limiting its industrial application.In a very recent work of the authors, the capability of SPIF process to successfully perform hole-flanges using a single-stage strategy has been experimentally investigated. The aim of the present work is to develop a numerical model of this process to beable to predict the sheet failure as a function of the size of the pre-cut hole. The numerical results are compared and discussed in the light of experimental tests over AA7075-O metal sheets with 1.6mm thickness.Ministerio de Economía y Competitividad DPI2015-64047-

Marine debris ingestion by albatrosses in the southwest Atlantic Ocean

Plastics and other marine debris affect wildlife through entanglement and by ingestion. We assessed the ingestion of marine debris by seven albatross species in the southwest Atlantic by analyzing stomach contents of birds killed in fisheries. Of the 128 specimens examined, including four Diomedea species (n = 78) and three Thalassarche species (n = 50), 21 (16.4%) contained 1–4 debris items, mainly in the ventriculus. The most common type was plastic fragments. Debris was most frequent in Diomedea species (25.6%) and, particularly, Diomedea sanfordi (38.9%) and very rare in Thalassarche species (2.0%), presumably reflecting differences in foraging behavior or distribution. Frequency of occurrence was significantly higher in male than female Diomedea albatrosses (39.3% vs. 18.0%). Although levels of accumulated debris were relatively low overall, and unlikely to result in gut blockage, associated toxins might nevertheless represent a health risk for Diomedea albatrosses, compounding the negative impact of other human activities on these threatened species

The foot-and-mouth disease RNA virus as a model in experimental phylogenetics

Phylogenetic reconstruction methods are subject to two types of limitations: our knowledge about the true history of organisms and the gross simplification implied in the numerical simulation models of the relationships between them. In such a situation, experimental phylogenetics provides a way to assess the accuracy of the phylogenetic reconstruction methods. Nonetheless, this capacity is only feasible for organisms in which replication and mutation rates are high enough to provide valuable data. On the other hand, experimental phylogenetics also provides insights on the main evolutionary processes acting on viral variability under different population dynamics. Our study with the foot-and-mouth disease virus (FMDV) strongly suggests that the phylogenetic reconstruction methods can infer erroneous phylogenies due to nucleotide convergences between isolates belonging to different experimental lineages. We also point out that the diverse evolutionary mechanisms acting in different experimental dynamics generate alterations and change the frequencies of genetic variants, which can lead to the misinterpretation of the real evolutionary history

Confident methods for the evaluation of the hydrogen content in nanoporous carbon microfibers

Abstract Nanoporous carbon microfibers were grown by chemical vapor deposition in the vapor-liquid solid mode using different fluid hydrocarbons as precursors in different proportions. The as-grown samples were further treated in argon and hydrogen atmospheres at different pressure conditions and annealed at several temperatures in order to deduce the best conditions for the incorporation and re-incorporation of hydrogen into the microfibers through the nanopores. Since there are some discrepancies in the results on the hydrogen content obtained under vacuum conditions, in this work, we have measured the hydrogen content in the microfibers using several analytical methods in ambient conditions: surface tension, mass density, and Raman measurements. A discussion on the validity of the results obtained through the correlation between them is the purpose of the present work.Peer Reviewe

Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D

The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB- 231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data the SAR study concluded that more than 75% of the open-chain Lam-D analogs tested showed cytotoxicity in a low micromolar GI50 range

RPS4Y gene family evolution in primates

Background: The RPS4 gene codifies for ribosomal protein S4, a very well-conserved protein present in all kingdoms. In primates, RPS4 is codified by two functional genes located on both sex chromosomes: the RPS4X and RPS4Y genes. In humans, RPS4Y is duplicated and the Y chromosome therefore carries a third functional paralog: RPS4Y2, which presents a testis-specific expression pattern. Results: DNA sequence analysis of the intronic and cDNA regions of RPS4Y genes from species covering the entire primate phylogeny showed that the duplication event leading to the second Y-linked copy occurred after the divergence of New World monkeys, about 35 million years ago. Maximum likelihood analyses of the synonymous and non-synonymous substitutions revealed that positive selection was acting on RPS4Y2 gene in the human lineage, which represents the first evidence of positive selection on a ribosomal protein gene. Putative positive amino acid replacements affected the three domains of the protein: one of these changes is located in the KOW protein domain and affects the unique invariable position of this motif, and might thus have a dramatic effect on the protein function. Conclusion: Here, we shed new light on the evolutionary history of RPS4Y gene family, especially on that of RPS4Y2. The results point that the RPS4Y1 gene might be maintained to compensate gene dosage between sexes, while RPS4Y2 might have acquired a new function, at least in the lineage leading to humans

Highly Enantioselective Iridium(I)-Catalyzed Hydrocarbonation of Alkenes: A Versatile Approach to Heterocyclic Systems Bearing Quaternary Stereocenters

We report a versatile, highly enantioselective intramolecular hydrocarbonation reaction that provides a direct access to heteropolycyclic systems bearing chiral quaternary carbon stereocenters. The method, which relies on an iridium(I)/bisphosphine chiral catalyst, is particularly efficient for the synthesis of five-, six- and seven-membered fused indole and pyrrole products, bearing one and two stereocenters, with enantiomeric excesses of up to >99 %. DFT computational studies allowed to obtain a detailed mechanistic profile and identify a cluster of weak non-covalent interactions as key factors to control the enantioselectivityThis work received financial support from the Spanish MINECO (SAF2016-76689-R, PID2019-108624RB-I00, CTQ2017-84767-P, PID2020-118579GB-I00), the Xunta de Galicia (ED431C 2017/19, 2015-CP082, Centro Singular de Investigación de Galicia accreditation 2019-2022, ED431G 2019/03, a predoctoral Fellowship to A. A. and M. C. and a postdoctoral Fellowship to D. F. F, ED481B-2019-005) and the ERDF, ERC (Adv. Grant No. 340055). The Orfeo-Cinqa network (CTQ2016-81797-REDC)S

Brief update on the satellite tagging of Atlantic swordfish

This paper provides a brief update of the study on habitat use for swordfish, developed within the working plan of the Swordfish Species Group of ICCAT. A total of 9 miniPAT tags have been deployed by observers on Portuguese and Spanish vessels and the Uruguayan research cruise in the North and South Atlantic. Data from eight tags/specimens are available, four specimens suffered from post-release mortality and one individual tag pop-up date has not occurred yet. These preliminary results showed swordfish moved in several directions, travelling considerable distances. Swordfish spent most of the daytime in deeper waters, being closer to the surface during night-time. The main plan for the next phase of the project is to continue the tag deployment during 2020 in several regions of the Atlantic Ocean and Mediterranean Sea

Clonal hematopoiesis is not prevalent in Hutchinson-Gilford progeria syndrome.

Clonal hematopoiesis of indeterminate potential (CHIP), defined as the presence of somatic mutations in cancer-related genes in blood cells in the absence of hematological cancer, has recently emerged as an important risk factor for several age-related conditions, especially cardiovascular disease. CHIP is strongly associated with normal aging, but its role in premature aging syndromes is unknown. Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare genetic condition driven by the accumulation of a truncated form of the lamin A protein called progerin. HGPS patients exhibit several features of accelerated aging and typically die from cardiovascular complications in their early teens. Previous studies have shown normal hematological parameters in HGPS patients, except for elevated platelets, and low levels of lamin A expression in hematopoietic cells relative to other cell types in solid tissues, but the prevalence of CHIP in HGPS remains unexplored. To investigate the potential role of CHIP in HGPS, we performed high-sensitivity targeted sequencing of CHIP-related genes in blood DNA samples from a cohort of 47 HGPS patients. As a control, the same sequencing strategy was applied to blood DNA samples from middle-aged and elderly individuals, expected to exhibit a biological age and cardiovascular risk profile similar to HGPS patients. We found that CHIP is not prevalent in HGPS patients, in marked contrast to our observations in individuals who age normally. Thus, our study unveils a major difference between HGPS and normal aging and provides conclusive evidence that CHIP is not frequent in HGPS and, therefore, is unlikely to contribute to the pathophysiology of this accelerated aging syndrome.This work was supported by Fundación “la Caixa” (grant number LCF/PR/HR17/52150007 to VF, and JJF). JJF is supported by a Ramón y Cajal award (RYC2016–20026) from the Spanish Ministerio de Ciencia e Innovación (MICIN)/Agencia Estatal de Investigación (AEI)/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro”. VA’s lab is supported by MICIN/ AEI/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro” (grant number PID2019-108489RBI00), the Progeria Research Foundation (Award PRF 2019–77), and a donation from Asociación Progeria Alexandra Peraut. LBG is supported by The Progeria Research Foundation. MDD is supported by a predoctoral FPI fellowship from the Spanish MICIN/AEI/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro” (PRE2019-087463), and MA-P is supported by a predoctoral FPU contract from the Ministerio de Educación, Cultura y Deporte (FPU18/02913). The CNIC is supported by the MICIN, the Instituto de Salud Carlos III, the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant number CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).S

Efficacy and Safety of Reslizumab in Patients with Severe Asthma with Inadequate Response to Omalizumab : A Multicenter, Open-Label Pilot Study

Funding: This study was endorsed by the Asthma Research Program of the Spanish Respiratory Society (PII de Asma de SEPAR) supported by a grant from Teva Pharmaceutical Industries.Background: Patients with severe allergic and eosinophilic asthma could qualify for different biologic therapies. Objective: To evaluate the efficacy and safety of weight-based intravenous reslizumab dosing in patients who have previously failed therapy with omalizumab. Methods: We carried out a 24-week prospective, multicenter, open-label, single-group, self-controlled study in patients with severe eosinophilic asthma who had previously failed to respond to omalizumab. The main objective was to determine whether treatment with reslizumab significantly improved asthma symptoms assessed by the Asthma Control Test (ACT) at week 24. Secondary objectives were to evaluate symptoms at weeks 4 and 12, change in FEV at week 24, and the incidence of severe exacerbations over the study period. Results: Twenty-nine patients (62.1% women, median age, 50.8 years) were included in the study. The median ACT score significantly increased from 13.0 (interquartile range, 8.0-18.0) at baseline to 21.0 (interquartile range, 14.0-24.0) at 24 weeks (P =.002). Only 2 of 29 patients developed at least 1 severe exacerbation during follow-up and none of them required hospitalization. Overall, 15 of 25 patients (60%) were considered as being controlled (ACT score of ≥20 and no exacerbations) at week 24. The percentage of patients who were receiving daily systemic corticosteroids significantly decreased from 72.4% to 52.0% (P =.019). Adverse events were mostly moderate and within the range of previously reported side effects with reslizumab. Conclusion: Reslizumab is an effective and safe option for patients with severe eosinophilic asthma and a history of omalizumab failure