Multiscale modelling for fusion and fission materials: the M4F project

The M4F project brings together the fusion and fission materials communities working on the prediction of radiation damage production and evolution and its effects on the mechanical behaviour of irradiated ferritic/martensitic (F/M) steels. It is a multidisciplinary project in which several different experimental and computational materials science tools are integrated to understand and model the complex phenomena associated with the formation and evolution of irradiation induced defects and their effects on the macroscopic behaviour of the target materials. In particular the project focuses on two specific aspects: (1) To develop physical understanding and predictive models of the origin and consequences of localised deformation under irradiation in F/M steels; (2) To develop good practices and possibly advance towards the definition of protocols for the use of ion irradiation as a tool to evaluate radiation effects on materials. Nineteen modelling codes across different scales are being used and developed and an experimental validation programme based on the examination of materials irradiated with neutrons and ions is being carried out. The project enters now its 4th year and is close to delivering high-quality results. This paper overviews the work performed so far within the project, highlighting its impact for fission and fusion materials science.This work has received funding from the Euratom research and training programme 2014-2018 under grant agreement No. 755039 (M4F project)

Staphylococcal phenotypes induced by naturally occurring and synthetic membrane-interactive polyphenolic β-lactam resistance modifiers.

Galloyl catechins, in particular (-)-epicatechin gallate (ECg), have the capacity to abrogate β-lactam resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA); they also prevent biofilm formation, reduce the secretion of a large proportion of the exoproteome and induce profound changes to cell morphology. Current evidence suggests that these reversible phenotypic traits result from their intercalation into the bacterial cytoplasmic membrane. We have endeavoured to potentiate the capacity of ECg to modify the MRSA phenotype by stepwise removal of hydroxyl groups from the B-ring pharmacophore and the A:C fused ring system of the naturally occurring molecule. ECg binds rapidly to the membrane, inducing up-regulation of genes responsible for protection against cell wall stress and maintenance of membrane integrity and function. Studies with artificial membranes modelled on the lipid composition of the staphylococcal bilayer indicated that ECg adopts a position deep within the lipid palisade, eliciting major alterations in the thermotropic behaviour of the bilayer. The non-galloylated homolog (-)-epicatechin enhanced ECg-mediated effects by facilitating entry of ECg molecules into the membrane. ECg analogs with unnatural B-ring hydroxylation patterns induced higher levels of gene expression and more profound changes to MRSA membrane fluidity than ECg but adopted a more superficial location within the bilayer. ECg possessed a high affinity for the positively charged staphylococcal membrane and induced changes to the biophysical properties of the bilayer that are likely to account for its capacity to disperse the cell wall biosynthetic machinery responsible for β-lactam resistance. The ability to enhance these properties by chemical modification of ECg raises the possibility that more potent analogs could be developed for clinical evaluation

Molecular dynamics simulations of non-equilibrium systems

Peer reviewe

Blown pack spoilage in vacuum-packaged meat: a review on clostridia as causative agents, sources, detection methods, contributing factors and mitigation strategies

Blown pack spoilage has been attributed almost exclusively to the growth of psychrophilic and psychrotolerant clostridia (PPC). It is the cause of great losses for meat industry. This spoilage is mainly caused by Clostridium estertheticum and it is characterised by a putrid odour, and production of large volumes of gas (mainly carbon dioxide and hydrogen), which result in severe distention of the packaging. Scope and approach This review summarizes the characteristics of blown pack spoilage caused by psychrophilic and psychrotolerant clostridia, factors affecting the occurrence of this spoilage, sources of contamination, methods of identification and preventive measures. A critical assessment on research needs related to blown pack spoilage is also presented. Key findings and conclusions In spite of recent developments, numerous facets related to blown pack spoilage research remain unclear. There is limited data on incidence and influencing factors for occurrence of spores and vegetative cells of PPC in meat and abattoir environment. In order to address this aspect, improvements in detection, isolation and typing methods are needed. Besides, more studies on source tracking of PPC from farm to abattoir are demanded. Finally, it is proposed that the reduction of losses due to blown pack spoilage should be achieved through the implementation of an integrated program that takes into account pre- and post-packaging mitigation strategies52123138CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP#302763/2014-7Sem informação#13/27118-1; #14/25028-

Combining reformulation, active packaging and non-thermal post-packaging decontamination technologies to increase the microbiological quality and safety of cooked ready-to-eat meat products

Cooked ready-to-eat (RTE) meat products are subjected to contamination of spoilage microorganisms such as lactic acid bacteria and pathogens such as Listeria monocytogenes. These microorganisms contaminate cooked RTE meat products after the cooking step and may further grow during shelf-life potentially leading to spoilage or foodborne diseases, respectively. In the current context of salt, fat and chemical preservatives reduction in meat products formulations, a combined strategy that considers the development of more robust formulations, active packaging and the use of non-thermal post-packaging decontamination strategies seems required to ensure shelf-stable and safe RTE cooked food products. Scope and approach The main objective of this review was to discuss the aspects related to reformulation, active packaging and the application of non-thermal decontamination technologies at the post-packaging step of cooked RTE meat products, their advantages, limitations and main challenges for their implementation. Key findings and conclusions In general, post-packaging decontamination technologies aim to reduce or inactivate pathogens and spoilage microorganisms present on the surface of ready-to-eat meat products. Low-temperature plasma, high-pressure processing (HPP), pulsed electric fields, pulsed ultraviolet light and ultrasound are promising alternatives in this segment. However, the choice of the most appropriate approach for post-packaging decontamination of cooked ready-to-eat meat products depends on the type of product and the technological objectives. Meat products formulation and packaging material properties should be considered while defining a post-packaging decontamination approach. Although they are advantageous, non-thermal technologies may present certain limitations such as the increase of oxidative reactions over the shelf-life724561CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP#150090/2016-1; #302763/2014-7#165710; # 33003017027P1; #33003017027P1#14/25028-

Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors

Inhibidor d'AKT; Càncer avançat; Fase IInhibidor de AKT; Cáncer avanzado; Fase IAKT inhibitor; Advanced cancer; Phase IBackground This phase Ib study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the oral AKT inhibitor ipatasertib and chemotherapy or hormonal therapy in patients with advanced or metastatic solid tumors to determine combined dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase II doses and schedules. Patients and methods The clinical study comprised four combination treatment arms: arm A (with docetaxel), arm B [with mFOLFOX6 (modified leucovorin, 5-fluorouracil, and oxaliplatin)], arm C (with paclitaxel), and arm D (with enzalutamide). Primary endpoints were safety and tolerability; secondary endpoints were pharmacokinetics, clinical activity per Response Evaluation Criteria in Solid Tumors v1.1, and prostate-specific antigen levels. Results In total, 122 patients were enrolled. Common adverse events were diarrhea, nausea, vomiting, decreased appetite, and fatigue. The safety profiles of the combination regimens were consistent with those of the background regimens, except for diarrhea, hyperglycemia, and rash, which were previously observed with ipatasertib treatment. The only combination DLT across all treatment arms was one event of grade 3 dehydration (ipatasertib 600 mg and paclitaxel). Recommended phase II doses for ipatasertib were 600 mg (and mFOLFOX6) and 400 mg (and paclitaxel), respectively. The maximum assessed dose of ipatasertib 600 mg combined with docetaxel or enzalutamide was well tolerated. Coadministration with enzalutamide (a cytochrome P450 3A inducer) resulted in approximately 50% lower ipatasertib exposure. Conclusions Ipatasertib in combination with chemotherapy or hormonal therapy was well tolerated with a safety profile consistent with that of ATP-competitive AKT inhibitors.This work was supported by Genentech, Inc., a member of the Roche Group, and F. Hoffmann-La Roche Ltd. (no grant number)