Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model

Microgravity impairs tissue organization and critical pathways involved in the cell–microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization.     

A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.     

A contribution to the evaluation of the reliability of iterative‐execution software †

This paper deals with the reliability of software executed iteratively, as for example in process control applications. The probability of mission survival is evaluated taking account of two characteristics of iterative software: (a) system failure, defined in terms of the behaviour of the software over successive iterations, because the controlled system can usually tolerate short bursts of errors; (b) the probabilistic correlation between successive executions of the software, which is to be expected for various reasons. The paper presents models accounting for these characteristics and evaluates their effects. The interesting case of fault‐tolerant software is considered as well. Using the example of a ‘pair‐and‐spare’ type fault‐tolerant scheme, the relationships between different aspects of failure behaviour that are covered by the models developed here, and those used elsewhere for fault‐tolerant software, are shown. Copyright © 1999 John Wiley & Sons, Ltd.     

The unrecognized occupational relevance of the interaction between engineered nanomaterials and the gastro-intestinal tract: a consensus paper from a multidisciplinary working group

Background

There is a fundamental gap of knowledge on the health effects caused by the interaction of engineered nanomaterials (ENM) with the gastro-intestinal tract (GIT). This is partly due to the incomplete knowledge of the complex physical and chemical transformations that ENM undergo in the GIT, and partly to the widespread belief that GIT health effects of ENM are much less relevant than pulmonary effects.However, recent experimental findings, considering the role of new players in gut physiology (e.g. the microbiota), shed light on several outcomes of the interaction ENM/GIT. Along with this new information, there is growing direct and indirect evidence that not only ingested ENM, but also inhaled ENM may impact on the GIT. This fact, which may have relevant implications in occupational setting, has never been taken into consideration.This review paper summarizes the opinions and findings of a multidisciplinary team of experts, focusing on two main aspects of the issue: 1) ENM interactions within the GIT and their possible consequences, and 2) relevance of gastro-intestinal effects of inhaled ENMs. Under point 1, we analyzed how luminal gut-constituents, including mucus, may influence the adherence of ENM to cell surfaces in a size-dependent manner, and how intestinal permeability may be affected by different physico-chemical characteristics of ENM. Cytotoxic, oxidative, genotoxic and inflammatory effects on different GIT cells, as well as effects on microbiota, are also discussed.Concerning point 2, recent studies highlight the relevance of gastro-intestinal handling of inhaled ENM, showing significant excretion with feces of inhaled ENM and supporting the hypothesis that GIT should be considered an important target of extrapulmonary effects of inhaled ENM.

Conclusions

In spite of recent insights on the relevance of the GIT as a target for toxic effects of nanoparticles, there is still a major gap in knowledge regarding the impact of the direct versus indirect oral exposure. This fact probably applies also to larger particles and dictates careful consideration in workers, who carry the highest risk of exposure to particulate matter.

     

A tour of secure software engineering solutions for connected vehicles

The growing number of vehicles daily moving on roads increases the need of protecting the safety and security of passengers, pedestrians, and vehicles themselves. This need is intensified when considering the pervasive introduction of Information and Communication Technologies (ICT) systems into modern vehicles, because this makes such vehicles potentially vulnerable from the point of view of security. The convergence of safety and security requirements is one of the main outstanding research challenges in software-intensive systems. This work reviews existing methodologies and solutions addressing security issues in the automotive domain with a focus on the integration between safety and security aspects. In particular, we identify the main security issues with vehicular communication technologies and existing gaps between state-of-the-art methodologies and their implementation in the real world. Starting from a literature survey and referring to widely accepted standards of the domain, such as AUTOSAR and ISO 26262, we discuss research challenges and set baselines for a holistic secure-by-design approach targeting safety and security aspects all along the different phases of the development process of automotive software.     

Validation of the Raman lidar algorithm for quantifying aerosol extinction

To calculate aerosol extinction from Raman lidar data, it is necessary to evaluate the derivative of a molecular Raman signal with respect to range. The typical approach taken in the lidar community is to make an a priori assumption about the functional behavior of the data to calculate the derivative. It has previously been shown that the use of the chi-squared technique to determine the most likely functional behavior of the data prior to actually calculating the derivative eliminates the need for making a priori assumptions. Here that technique is validated through numerical simulation and by application to a significant body of Raman lidar measurements. In general, we show that the chi-squared approach for evaluating extinction yields lower extinction uncertainty than traditional techniques. We also use the technique to study the feasibility of developing a general characterization of the extinction uncertainty that could permit the uncertainty in Raman lidar aerosol extinction measurements to be estimated accurately without the need of the chi-squared technique.     

Aerobic composting of tobacco industry solid waste—simulation of the process

Solid waste accumulated during the processing of tobacco for cigarette manufacture mostly contains tobacco particles and flavoring agents. Its main characteristics are a high content of nicotine (2,000 mg per kg of total solids), which is a toxic compound, and high value of total organic carbon of the aqueous extract (12,620.0 mg l^–1). Because of this fact tobacco waste cannot be disposed of with urban waste.The aim of this work was to stabilize tobacco solid waste by aerobic composting. The experiments were carried out in closed thermally insulated column reactors (1.0 l and 25 l) under adiabatic conditions and at an airflow rate of 0.9 l min^–1 kg^–1 of volatile solids for 16 days. During the process, temperature changes in the reactor, CO₂ production and the numbers of mesophilic and thermophilic organisms in the mixed microbial culture were closely monitored. Nicotine concentration in the samples was analyzed at the start and at the end of process. It was estimated that at the end of composting the volume and mass of total solids in the tobacco waste were reduced by about 50% and those of nicotine by 80%. A simple empirical model was used to simulate the biodegradation rate of the organic fraction of the solid waste. It was found that the selected model describes aerobic composting fairly well, although only two kinetic parameters (k₀ and n) were estimated.List of symbols c_pS specific heat capacity of the substrate, kJ kg^–1 K^–1 - c_pz specific heat capacity of air, kJ kg^–1 K^–1 - F_Ku and F_Ki molar airflow at the reactor inlet and outlet, mol h^–1 - H_r reaction enthalpy, kJ kg^–1 of dry substrate - k specific rate, Eqs. (5) and (9), h^–1 - k_o constant in Eq. (9), day^–1 - m_o initial mass of the substrate, kg - m_S mass of dry substrate, kg - n order of the reaction in Eq. (5) - n_K molar amount of oxygen, mol - Q_v airflow volume, m³ h^–1 - r_K oxygen depletion rate, mol kg^–1 h^–1 - r_S degradation rate, kg kg^–1 h^–1 - _z air density, kg m^–3 - SD mean square deviation - t time, h - T temperature in reactor, °C - T_o temperature of substrate at the beginning of reaction, °C - T_K temperature of compost at the end of reaction, °C - T_u temperature of air at the reactor inlet - space time, day - w_S mass fraction of compost, m_sm_o^–1, kg kg^–1     

Role of Carbonic Anhydrase in Cerebral Ischemia and Carbonic Anhydrase Inhibitors as Putative Protective Agents

Ischemic stroke is a leading cause of death and disability worldwide. The only pharmacological treatment available to date for cerebral ischemia is tissue plasminogen activator (t-PA) and the search for successful therapeutic strategies still remains a major challenge. The loss of cerebral blood flow leads to reduced oxygen and glucose supply and a subsequent switch to the glycolytic pathway, which leads to tissue acidification. Carbonic anhydrase (CA, EC 4.2.1.1) is the enzyme responsible for converting carbon dioxide into a protons and bicarbonate, thus contributing to pH regulation and metabolism, with many CA isoforms present in the brain. Recently, numerous studies have shed light on several classes of carbonic anhydrase inhibitor (CAI) as possible new pharmacological agents for the management of brain ischemia. In the present review we summarized pharmacological, preclinical and clinical findings regarding the role of CAIs in strokes and we discuss their potential protective mechanisms.