Jacobi stability analysis of scalar field models with minimal coupling to gravity in a cosmological background

We perform the study of the stability of the cosmological scalar field models, by using the Jacobi stability analysis, or the Kosambi-Cartan-Chern (KCC) theory. In the KCC approach we describe the time evolution of the scalar field cosmologies in geometric terms, by performing a "second geometrization", by considering them as paths of a semispray. By introducing a non-linear connection and a Berwald type connection associated to the Friedmann and Klein-Gordon equations, five geometrical invariants can be constructed, with the second invariant giving the Jacobi stability of the cosmological model. We obtain all the relevant geometric quantities, and we formulate the condition of the Jacobi stability for scalar field cosmologies in the second order formalism. As an application of the developed methods we consider the Jacobi stability properties of the scalar fields with exponential and Higgs type potential. We find that the Universe dominated by a scalar field exponential potential is in Jacobi unstable state, while the cosmological evolution in the presence of Higgs fields has alternating stable and unstable phases. By using the standard first order formulation of the cosmological models as dynamical systems we have investigated the stability of the phantom quintessence and tachyonic scalar fields, by lifting the first order system to the tangent bundle. It turns out that in the presence of a power law potential both these models are Jacobi unstable during the entire cosmological evolution.Comment: 24 pages, 14 figures, accepted for publication in Advances in High Energy Physics, special issue "Dark Physics in the Early Universe

EvoMaster: A Search-Based System Test Generation Tool

Testing web/enterprise applications is complex and expensive when done manually. Often, software testing takes up to half of the development time and cost for a system. So much testing is needed because the cost of software failure is simply too large: for example, in 2017, 304 software failures (reported in the media) impacted 3.6 billion people and $1.7 trillion in assets worldwide (Tricentis, 2017). Unfortunately, due to its high cost, software testing is often left incomplete, and only applied partially.To address this problem, in Software Engineering (SE) research a lot of effort has been spent in trying to design and implement novel techniques aimed at automating several different tasks, where software testing is among the most studied tasks. Search-Based Software Test- ing (SBST) (Harman et al., 2012) casts the problem of software testing as an optimization problem, aimed at, for example, maximizing code coverage and fault detection.Our SBST tool called EvoMaster addresses these challenges by using evolutionary techniques to automatically generate test cases. It currently focuses on RESTful web services, which are the pillars of modern web and enterprise applications (Allamaraju, 2010; Fielding, 2000).Fil: Arcuri, Andrea. Kristiania University College; NoruegaFil: Galeotti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Investigación en Ciencias de la Computación. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Investigación en Ciencias de la Computación; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; ArgentinaFil: Marculescu, Bogdan. Kristiania University College; NoruegaFil: Zhang, Man. Kristiania University College; Norueg

Building an open-source system test generation tool: lessons learned and empirical analyses with EvoMaster

Research in software testing often involves the development of software prototypes. Like any piece of software, there are challenges in the development, use and verification of such tools. However, some challenges are rather specific to this problem domain. For example, often these tools are developed by PhD students straight out of bachelor/master degrees, possibly lacking any industrial experience in software development. Prototype tools are used to carry out empirical studies, possibly studying different parameters of novel designed algorithms. Software scaffolding is needed to run large sets of experiments efficiently. Furthermore, when using AI-based techniques like evolutionary algorithms, care needs to be taken to deal with their randomness, which further complicates their verification. The aforementioned represent some of the challenges we have identified for this domain. In this paper, we report on our experience in building the open-source EvoMaster tool, which aims at system-level test case generation for enterprise applications. Many of the challenges we faced would be common to any researcher needing to build software testing tool prototypes. Therefore, one goal is that our shared experience here will boost the research community, by providing concrete solutions to many development challenges in the building of such kind of research prototypes. Ultimately, this will lead to increase the impact of scientific research on industrial practice.publishedVersio

Carbamazepine-induced DRESS syndrome: a case report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening, idiosyncratic, acute adverse drug reaction. Fever, morbilliform cutaneous eruption, and eosinophilia are essential features for the diagnosis of this syndrome, along with significant multisystem involvement, hepatitis being the most common, followed by nephritis. The pathogenesis of DRESS syndrome is not yet fully understood. Several hypotheses have been proposed which support the involvement of an intricate interplay of multiple factors. We report a clinical case of DRESS syndrome with renal injury, induced by carbamazepine, in a patient with alcohol abstinence syndrome. In order to define the case, the RegiSCAR score and the Japanese Group score, used in the diagnosis of drug-induced hypersensitivity, were applied. DRESS syndrome is a potentially fatal disease, with a mortality that can reach up to 40% of cases. This condition endangers the patient\u27s life by affecting the internal organs, mainly the liver, kidneys, heart, and lungs. Our case attempts to increase awareness among physicians about this serious disease and the importance of early diagnosis, especially since carbamazepine is a commonly used anticonvulsant drug

Nitrogen-doped graphene as metal free basic catalyst for coupling reactions

[EN] N-doped defective graphene [(N)G] obtained by pyrolysis at 900 degrees C of chitosan contains about 3.7% of residual N atoms, distributed as pyridinic, pyrrolic and graphitic N atoms. It has been found that (N)G acts as basic catalyst promoting two classical C-C bond forming nucleophilic additions in organic chemistry, such as the Michael and the Henry additions. Computational calculations at DFT level of models corresponding to the various N atoms leads to the conclusion that N atoms are more stable at the periphery of the graphene sheets and that H adsorption on these sites is a suitable descriptor to correlate with the catalytic activity of the various sites. According to these calculations the most active sites are pyridinic N atoms at zig-zag edges of the sheets. In addition, N as dopant changes the reactivity of the neigh. bour C atoms. Water was found a suitable solvent to achieve high conversions in both reactions. In this solvent the initial distribution of N atoms is affected due to the easy protonation of the N-py to N-pyH sites. As an effect, C edge sites adjacent at N-PyH with an appropriate reactivity towards the alpha-C-H bond breaking are formed. The present results show the general activity of N-doped graphene as base catalysts and illustrate the potential of carbocatalysis to promote reactions of general interest in organic synthesis. (C) 2019 Elsevier Inc. All rights reserved.This work was supported by UEFISCDI (PN-III-P4-ID-PCE-2016-0146. nr. 121/2017 and project number PN-III-P1-1.1-TE-2016-2191. nr. 89/2018). Financial support by the Spanish Ministry of Economy and Competitiveness (Severo Ochoa and CTQ2015-69653-CO2-R1) and Generalitat Valenciana (Prometeo 2017-083) is gratefully acknowledged. A.P thanks the Spanish Ministry of Science and Innovation for a Ramon y Cajal research associate contract.Candu, N.; Man, I.; Andrada, S.; Cojocaru, B.; Coman, SM.; Bucur, C.; Primo Arnau, AM.... (2019). Nitrogen-doped graphene as metal free basic catalyst for coupling reactions. Journal of Catalysis. 376:238-247. https://doi.org/10.1016/j.jcat.2019.07.011S23824737

Towards Rocket Engine Components with Increased Strength and Robust Operating Characteristics

High-energy rotating machines, powering liquid propellant rocket engines, are subject to various sources of high and low cycle fatigue generated by unsteady flow phenomena. Given the tremendous need for reliability in a sustainable space exploration program, a fundamental change in the design methodology for engine components is required for both launch and space based systems. A design optimization system based on neural-networks has been applied and demonstrated in the redesign of the Space Shuttle Main Engine (SSME) Low Pressure Oxidizer Turbo Pump (LPOTP) turbine nozzle. One objective of the redesign effort was to increase airfoil thickness and thus increase its strength while at the same time detuning the vane natural frequency modes from the vortex shedding frequency. The second objective was to reduce the vortex shedding amplitude. The third objective was to maintain this low shedding amplitude even in the presence of large manufacturing tolerances. All of these objectives were achieved without generating any detrimental effects on the downstream flow through the turbine, and without introducing any penalty in performance. The airfoil redesign and preliminary assessment was performed in the Exploration Technology Directorate at NASA ARC. Boeing/Rocketdyne and NASA MSFC independently performed final CFD assessments of the design. Four different CFD codes were used in this process. They include WIL DCA T/CORSAIR (NASA), FLUENT (commercial), TIDAL (Boeing Rocketdyne) and, a new family (AardvarWPhantom) of CFD analysis codes developed at NASA MSFC employing LOX fluid properties and a Generalized Equation Set formulation. Extensive aerodynamic performance analysis and stress analysis carried out at Boeing Rocketdyne and NASA MSFC indicate that the redesign objectives have been fully met. The paper presents the results of the assessment analysis and discusses the future potential of robust optimal design for rocket engine components

Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries. Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls. Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold. Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Effects of thermal water inhalation in chronic upper respiratory tract infections in elderly and young patients

Background: Chronic upper respiratory tract infections (cURTI) are very frequent illnesses which occur at any age of life. In elderly, cURTI are complicated by immunosenescence, with involvement of lung immune responsiveness. Results: In the present study, 51 elderly (age range: 66-86) and 51 young (age range 24-58) cURTI patients underwent a single cycle (two weeks) of inhalatory therapy with salt-bromide-iodine thermal water in the thermal station "Margherita di Savoia" (Margherita di Savoia, BAT, Italy). Peripheral blood serum cytokines and clinical assessment were performed before therapy (T0) and after six months (T1) and 12 months (T2) from inhalatory treatment. In both elderly and young patients, at baseline an increased release of T helper (h)1-related cytokines [interleukin (IL)-2 and interferon-γ] and of Th2-related cytokine (IL-4) was documented. Inhalatory treatment reduced the excessive secretion of all the above-cited cytokines. IL-10 values were above normality at all times considered in both groups of patients. In addition, an increase in IL-17 and IL-21 serum levels following therapy was observed in both groups of patients. Pro-inflammatory cytokine (IL-1β, IL-6, IL-8 and tumor necrosis factor-α) baseline values were lower than normal values at T0 in both elderly and young cURTI patients. Their levels increased following inhalatory treatment. Clinically, at T2 a dramatic reduction of frequency of upper respiratory tract infections was recorded in both groups of patients. Conclusion: Thermal water inhalation is able to modulate systemic immune response in elderly and young cURTI patients, thus reducing excessive production of Th1 and Th2-related cytokines, on the one hand. On the other hand, increased levels of IL-21 (an inducer of Th17 cells) and of IL-17 may be interpreted as a protective mechanism, which likely leads to neutrophil recruitment in cURTI patients. Also restoration of pro-inflammatory cytokine release following inhalatory therapy may result in microbe eradication. Quite importantly, the maintenance of high levels of IL-10 during the follow-up would suggest a consistent regulatory role of this cytokine in attenuating the pro-inflammatory arm of the immune response