Along strike preorogenic thickness variation and onlapping geometries control on thrust wedge evolution: insight from sandbox analogue modelling

Abstract: Thickness variation of sedimentary sequences is largely viewed as a controlling factor on the evolution of orogenic wedges; among the different structural and stratigraphic features generating thickness variation, we focused our analysis on the onlapping geometries, using laboratory sandbox experiments. The aim was trying to describe how a common sedimentary configuration could influence thrusts geometry and mode of accretion. Model results showed that onlapping geometries in pretectonic sediments cause a great complexity, dominated by curvilinear thrusts, back thrust and out-ofsequence thrusts. They also influence mode of accretion, generating diachronous thrusting along strike, reactivation and under-thrusting alternating to simple piggy-back sequence. Our modeling results are compared with natural examples from the Apennines, the southern Pyrenees, the Pindos (Greece) and the West Spitsbergen (Greenland) fold and thrust belts, among many others, where strain localization and diachronic thrusting affecting thrust propagation in correspondence to complex geometries both in the pre-orogenic stratigraphy and in the upper crust

Setting the optimal sheet thickness distribution for plastics thermoforming by multi-objective optimization

Thermoforming is a thermoplastic processing technique commonly used in the rigid packaging industry. The process comprises a heating stage, which aims at allowing the sheet to acquire the required deformability, a deformation stage, in which the sheets conform to the mould surface, and, finally, a cooling stage, which allows the part to be extracted from the mould without distorting. Since there are several processing variables associated with those stages, optimizing the thermoforming process is a complex task. In this work, a multi-objective optimization evolutionary algorithm is proposed to optimize the plastics thermoforming process. For that purpose, the thickness distribution of the final part was optimized considering that it is manufactured from uniform temperature sheets with different thickness distributions, such as constant and spline and concentric profiles. The aims were to minimize the sheet volume, as it implies less material use; assure a minimum value for the part thickness distribution, to avoid hindering its mechanical behavior; and minimize the thickness heterogeneity, i.e., the difference between the thickness of the part and a reference thickness. The Pareto optimal solutions found by the algorithm correspond to different thickness profiles for the three different sheet shapes. In all cases, an improvement of the different profiles along the successive generations of the evolutionary algorithm was obtained, which are related to the objectives considered. Moreover, the initial sheet thickness distribution was found to clearly influence the optimization process. The results obtained for these three different initial sheet shapes indicate that the proposed methodology is valid, providing solutions with physical meaning and with great potential to be applied in more complex cases

Multi-objective optimization of plastics thermoforming

The practical application of a multi-objective optimization strategy based on evolutionary algorithms was proposed to optimize the plastics thermoforming process. For that purpose, in this work, differently from the other works proposed in the literature, the shaping step was considered individually with the aim of optimizing the thickness distribution of the final part originated from sheets characterized by different thickness profiles, such as constant thickness, spline thickness variation in one direction and concentric thickness variation in two directions, while maintaining the temperature constant. As far we know, this is the first work where such a type of approach is proposed. A multi-objective optimization strategy based on Evolutionary Algorithms was applied to the determination of the final part thickness distribution with the aim of demonstrating the validity of the methodology proposed. The results obtained considering three different theoretical initial sheet shapes indicate clearly that the methodology proposed is valid, as it provides solutions with physical meaning and with great potential to be applied in real practice. The different thickness profiles obtained for the optimal Pareto solutions show, in all cases, that that the different profiles along the front are related to the objectives considered. Also, there is a clear improvement in the successive generations of the evolutionary algorithm.This research was funded by NAWA-Narodowa Agencja Wymiany Akademickiej, under grant PPN/ULM/2020/1/00125 and European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No 734205–H2020-MSCA-RISE2016. The authors also acknowledge the funding by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT (Portuguese Foundation for Science and Technology) under the projects UID-B/05256/2020, UID-P/05256/2020, UIDB/00319/2020, MORPHING.TECH— Direct digital Manufacturing of automatic programmable and Continuously adaptable patterned surfaces with a discrete and patronized composition (POCI-01-0247-FEDER-033408)

New boundary conditions for simulating the filling stage of the injection molding process

Purpose The purpose of this paper is to develop new boundary conditions for simulating the injection molding process of polymer melts. Design/methodology/approach The boundary conditions are derived and implemented to simulate real-life air vents (used to allow the air escape from the mold). The simulations are performed in the computational libraryOpenFOAM (R) by considering two different fluid models, namely, Newtonian and generalized Newtonian (Bird-Carreau model). Findings A detailed study on the accuracy of the solverinterFoamfor simulating the filling stage is presented, by considering simple geometries and adaptive mesh refinement. The verified code is then used to study the three-dimensional filling of a more complex geometry. Originality/value The results obtained showed that the numerical method is stable and allows one to model the filling process, simulating the real injection molding process.This work is funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT (Portuguese Foundation for Science and Technology) under the projects UID-B/05256/2020, UID-P/05256/2020 and MOLDPRO-Aproximacoes multi-escala para moldacao por injecao de materiais plasticos (POCI-01-0145-FEDER-016665).The research of L.L. Ferras was partially financed by the Portuguese Funds through FCT within the Projects UID-B/00013/2020, UID-P/00013/2020 and the scholarship SFRH/BPD/100353/2014.The authors would like to acknowledge the Minho University Cluster (NORTE-07-0162-FEDER-000086) for providing the HPC resources that contributed to the research results reported within this paper

GW0742, a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice.

Peroxisome Proliferator-Activated Receptor β/δ belongs to a family of ligand-activated transcription factors. Recent data have clarified its metabolic roles and enhanced the potential role of this receptor as a pharmacological target. Moreover, although its role in acute inflammation remains unclear, being the nuclear receptor PPAR β/δ widely expressed in many tissues, including the vascular endothelium, we assume that the infiltration of PMNs into tissues, a prominent feature in inflammation, may also be related to PPAR β/δ. Mice subjected to intratracheal instillation of bleomycin (BLEO, 1 mg/kg), a glycopeptide produced by the bacterium Streptomyces verticillus, develop lung inflammation and injury characterized by a significant neutrophil infiltration and tissue oedema. Therefore, the aim of this study is to investigate the effects of GW0742, a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Our data showed that GW0742-treatment (0.3 mg/Kg, 10% DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of: 1) cytokine production; 2) leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity; 3) IκBα degradation and NF-κB nuclear translocation; 4) ERK phosphorylation; 5) stress oxidative by NO formation due to iNOS expression; 6) nitrotyrosine and PAR localization; 7) the degree of apoptosis, evaluated by Bax and Bcl2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO-instillation in mice

Monitoring campaign over an edible dormouse population (Glis glis; rodentia: Gliridae) in Sicily: First report of mesocestodiasis

This study reports on the health status of the edible dormouse (Glis glis) living in Nebrodi Park (Sicily, Italy), responsible for nut crop damage in the area. In the frame of a monitoring campaign for potential zoonotic risk involving 30 dormice, rectal and conjunctival swabs and fur and nest content were collected for bacteriological and parasitological examinations, respectively. A large presence of fleas belonging to Monopsyllus sciurorum was found. Necropsy of a dead dormouse revealed an infection of Mesocestoides lineatus, whose cysts were found in the abdomen cavity and on the liver; this is the first report of this in this species. Further studies are necessary to identify their role in the environment, considering the limited knowledge of this species in Italy

Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a multicenter cohort analysis.

The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging. METHODS: A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors. RESULTS: Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1-3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P < 0.001), absence of visceral metastases (P = 0.001), estrogen receptor positivity (P = 0.016), and low Ki-67 index (P = 0.024) were significantly associated with CR. In the first 48 h, 10.4 % of patients reported severe skin pain. Dermatologic toxicity included grade 3 skin ulceration (8.0 %) and grade 2 skin hyperpigmentation (8.8 %). Tumor 1-year local progression-free survival was 86.2 % (95 % confidence interval 79.3-93.8) and 96.4 % (95 % confidence interval 91.6-100) in the subgroup of those with CR. CONCLUSIONS: In this study, small tumor size, absence of visceral metastases, estrogen receptor positivity, and low Ki-67 index were predictors of CR after ECT. Patients who experienced CR had durable local control. ECT represents a valuable skin-directed therapy for selected patients with BC

ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment

Mechanisms underlying the resistance of acute lymphoblastic leukemia (ALL) blasts to L-asparaginase are still incompletely known. Here we demonstrate that human primary bone marrow mesenchymal stromal cells (MSCs) successfully adapt to L-asparaginase and markedly protect leukemic blasts from the enzyme-dependent cytotoxicity through an amino acid tradeoff. ALL blasts synthesize and secrete glutamine, thus increasing extracellular glutamine availability for stromal cells. In turn, MSCs use glutamine, either synthesized through glutamine synthetase (GS) or imported, to produce asparagine, which is then extruded to sustain asparagine-auxotroph leukemic cells. GS inhibition prevents mesenchymal cells adaptation to L-asparaginase, lowers glutamine secretion by ALL blasts, and markedly hinders the protection exerted by MSCs on leukemic cells. The pro-survival amino acid exchange is hindered by the inhibition or silencing of the asparagine efflux transporter SNAT5, which is induced in mesenchymal cells by ALL blasts. Consistently, primary MSCs from ALL patients express higher levels of SNAT5 (P &lt;.05), secrete more asparagine (P &lt;.05), and protect leukemic blasts (P &lt;.05) better than MSCs isolated from healthy donors. In conclusion, ALL blasts arrange a pro-leukemic amino acid trade-off with bone marrow mesenchymal cells, which depends on GS and SNAT5 and promotes leukemic cell survival during L-asparaginase treatment

What hinders the uptake of computerized decision support systems in hospitals? A qualitative study and framework for implementation

Background: Advanced Computerized Decision Support Systems (CDSSs) assist clinicians in their decision-making process, generating recommendations based on up-to-date scientific evidence. Although this technology has the potential to improve the quality of patient care, its mere provision does not guarantee uptake: even where CDSSs are available, clinicians often fail to adopt their recommendations. This study examines the barriers and facilitators to the uptake of an evidence-based CDSS as perceived by diverse health professionals in hospitals at different stages of CDSS adoption. Methods: Qualitative study conducted as part of a series of randomized controlled trials of CDSSs. The sample includes two hospitals using a CDSS and two hospitals that aim to adopt a CDSS in the future. We interviewed physicians, nurses, information technology staff and members of the boards of directors (n=30). We used a constant comparative approach to develop a framework for guiding implementation. Findings: We identified six clusters of experiences of, and attitudes towards CDSSs, which we label as ‘positions’. The six positions represent a gradient of acquisition of control over CDSSs (from low to high) and are characterized by different types of barriers to CDSS uptake. The most severe barriers (prevalent in the first positions) include clinicians’ perception that the CDSSs may reduce their professional autonomy or may be used against them in the event of medical-legal controversies. Moving towards the last positions, these barriers are substituted by technical and usability problems related with the technology interface. When all barriers are overcome, CDSSs are perceived as a working tool at the service of its users, integrating clinicians’ reasoning and fostering organizational learning. Discussion: Barriers and facilitators to the use of CDSSs are dynamic and may exist prior to their introduction in clinical contexts; providing a static list of obstacles and facilitators, irrespective of the specific implementation phase and context, may not be sufficient or useful to facilitate uptake. Factors such as clinicians’ attitudes towards scientific evidences and guidelines, the quality of inter-disciplinary relationships and an organizational ethos of transparency and accountability need to considered when exploring the readiness of a hospital to adopt CDSSs.This work is supported by the Italian Ministry of Health (GR-2009-1606736), Regione Lombardia (D.R.G. IX/4340 26/10/2012), and the Wellcome Trust (WT097899)