Memory Management for Real-Time Java: An Efficient Solution using Hardware Support*

This paper addresses the issue of improving the performance of memory management for real-time Java applications, building upon the real-time specification for Java (RTSJ) from the Real-Time Java Expert Group. In a first step, a collecting dynamic memory solution including both a real-time garbage collector and region-based memory management, is proposed. A thorough analysis of the parameters influencing the performance of write barriers in memory management, together with ways of improvement are then presented. Finally, the implementation of a memory management solution compliant with the RTSJ and integrating the proposed improvements is sketched.     

Revisiting the Roles of Filaggrin in Atopic Dermatitis

The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin.     

The Endothelium and COVID-19: An Increasingly Clear Link Brief Title: Endotheliopathy in COVID-19

The endothelium has a fundamental role in the cardiovascular complications of coronavirus disease 2019 (COVID-19). Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particularly affects endothelial cells. The virus binds to the angiotensin-converting enzyme 2 (ACE-2) receptor (present on type 2 alveolar cells, bronchial epithelial cells, and endothelial cells), and induces a cytokine storm. The cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 have particular effects on endothelial cells—leading to endothelial dysfunction, endothelial cell death, changes in tight junctions, and vascular hyperpermeability. Under normal conditions, apoptotic endothelial cells are removed into the bloodstream. During COVID-19, however, endothelial cells are detached more rapidly, and do not regenerate as effectively as usual. The loss of the endothelium on the luminal surface abolishes all of the vascular responses mediated by the endothelium and nitric oxide production in particular, which results in greater contractility. Moreover, circulating endothelial cells infected with SARS-CoV-2 act as vectors for viral dissemination by forming clusters that migrate into the circulation and reach distant organs. The cell clusters and the endothelial dysfunction might contribute to the various thromboembolic pathologies observed in COVID-19 by inducing the formation of intravascular microthrombi, as well as by triggering disseminated intravascular coagulation. Here, we review the contributions of endotheliopathy and endothelial-cell-derived extracellular vesicles to the pathogenesis of COVID-19, and discuss therapeutic strategies that target the endothelium in patients with COVID-19.     

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.     

Modelling collective decision making in groups and crowds: Integrating social contagion and interacting emotions, beliefs and intentions

Collective decision making involves on the one hand individual mental states such as beliefs, emotions and intentions, and on the other hand interaction with others with possibly different mental states. Achieving a satisfactory common group decision on which all agree requires that such mental states are adapted to each other by social interaction. Recent developments in social neuroscience have revealed neural mechanisms by which such mutual adaptation can be realised. These mechanisms not only enable intentions to converge to an emerging common decision, but at the same time enable to achieve shared underlying individual beliefs and emotions. This paper presents a computational model for such processes. As an application of the model, an agent-based analysis was made of patterns in crowd behaviour, in particular to simulate a real-life incident that took place on May 4, 2010 in Amsterdam. From available video material and witness reports, useful empirical data were extracted. Similar patterns were achieved in simulations, whereby some of the parameters of the model were tuned to the case addressed, and most parameters were assigned default values. The results show the inclusion of contagion of belief, emotion, and intention states of agents results in better reproduction of the incident than non-inclusion.     

A heuristic to solve the synchronized log-truck scheduling problem

We present a synchronized routing and scheduling problem that arises in the forest industry, as a variation of the log-truck scheduling problem. It combines routing and scheduling of trucks with specific constraints related to the Canadian forestry context. This problem includes aspects such as pick-up and delivery, multiple products, inventory stock, multiple supply points and multiple demand points. We developed a decomposition approach to solve the weekly problem in two phases. In the first phase we use a MIP solver to solve a tactical model that determines the destinations of full truckloads from forest areas to woodmills. In the second phase, we make use of two different methods to route and schedule the daily transportation of logs: the first one consists in using a constraint-based local search approach while the second one is a hybrid approach involving a constraint programming based model and a constraint-based local search model. These approaches have been implemented using COMET2.0. The method, was tested on two industrial cases from forest companies in Canada.     

Creep behavior of adhesives used for external FRP strengthening of RC structures

It is technologically possible to strengthen steel-reinforced concrete structures with externally bonded carbon–epoxy composites. The durability and performance of those reinforcements directly depend on the rheological behavior of the concrete–composite interface. We propose a methodology to evaluate the permissible shear stress of the interface, based on thermo-stimulated tensile shear tests performed on the interface, and taking into account the effects of time and temperature. Four polymers used for bonding were tested and a value for the permissible shear stress is proposed for each strengthening system.     

Influence of clay in limestone fillers for self-compacting cement based composites

High workability together with a good resistance to segregation is needed for cement based composites, specifically fresh self-compacting mortars (SCM); in this prospect, the amount of coarse materials has to be reduced and replaced by fine material. Several limestone fillers are here compared and analysed. These by-products are issued from different industrial sectors, such as the aggregate and lime production industry (quarrying operations) and the ornamental stones industry (sawing operations).Particular attention has been paid to clay content, as consistency of fresh mortars was varying, while other physical characteristics like granulometry remained the same. Relationship between the physico-chemical properties of the fillers and the properties of fresh and hardened mortars are brought forward. Even if it may affect fresh properties of mortars, results clearly show that clay type and content has minor influence than limestone filler itself.     

Error evaluation on experimental stress–strain curve obtained from tube bulging test

To get precise material data for advanced numerical modelling of tube hydroforming process, the tube bulging test is recommended. Stresses and strains in the tube cannot be evaluated easily and several approaches have been proposed. A review is proposed and points out their advantages and drawbacks.