Quantitative risk assessment on a hydrogen refuelling station

The Directive 2014/94/UE (DAFI, Alternative Fuel Initiative Directive) on the deployment of alternative fuels (i.e. hydrogen) infrastructures has been recently transposed into national law in Italy. Consequently, the technical regulation on fire prevention for H2fuelling stations has been updated, in order to consider the current maximum delivery pressure (700 bar) of gaseous hydrogen for road vehicles. This technical regulation establishes the prescriptive safety distance from a piece of equipment. In the case of a new station, an assessment of the frequency of the event and its potential consequences is necessary. This is to understand which risk can reasonably be mitigated by a safety distance or whether additional mitigation or prevention measures should be taken. This paper presents the quantitative risk assessment (QRA) study on a hydrogen station planned to be installed, study which aims at determining the safety distances. Such study utilizes the Sandia-developed QRA tool, Hydrogen Risk Analysis Model (HyRAM), to calculate risk values when developing risk-equivalent plans. HyRAM combines reduced order deterministic models that characterize hydrogen release and flame behavior with probabilistic risk models to quantify risk values. Thanks to HyRAM tool it is possible to estimate physical effects and consequences on people and structures and plants, related to risk scenarios, by means of a damage model library. Use of risk assessment may allow station owners and designers to flexibly define station-specific mitigations, with the purpose of achieving equal or better levels of safety with respect to prescriptive recommendation levels, as suggested by ISO19880-1 (2018)

Apricot melanoidins prevent oxidative endothelial cell death by counteracting mitochondrial oxidation and membrane depolarization

The cardiovascular benefits associated with diets rich in fruit and vegetables are thought to be due to phytochemicals contained in fresh plant material. However, whether processed plant foods provide the same benefits as unprocessed ones is an open question. Melanoidins from heat-processed apricots were isolated and their presence confirmed by colorimetric analysis and browning index. Oxidative injury of endothelial cells (ECs) is the key step for the onset and progression of cardiovascular diseases (CVD), therefore the potential protective effect of apricot melanoidins on hydrogen peroxide-induced oxidative mitochondrial damage and cell death was explored in human ECs. The redox state of cytoplasmic and mitochondrial compartments was detected by using the redox-sensitive, fluorescent protein (roGFP), while the mitochondrial membrane potential (MMP) was assessed with the fluorescent dye, JC-1. ECs exposure to hydrogen peroxide, dose-dependently induced mitochondrial and cytoplasmic oxidation. Additionally detected hydrogen peroxide-induced phenomena were MMP dissipation and ECs death. Pretreatment of ECs with apricot melanoidins, significantly counteracted and ultimately abolished hydrogen peroxide-induced intracellular oxidation, mitochondrial depolarization and cell death. In this regard, our current results clearly indicate that melanoidins derived from heat-processed apricots, protect human ECs against oxidative stress

Graphene sustained nonlinear modes in dielectric waveguides

We discuss the existence of nonlinear modes sustained by graphene layers in dielectric waveguides. Taking advantage of the almost two dimensional nature of graphene, we introduce the nonlinear effect as a parameter in the continuity equations. We then apply our modeling to a simple slab waveguide to enlighten how graphene can be used to induce huge nonlinear phase shifts at easily accessible power levels

Neutralizing antibodies against IFN‐β in multiple sclerosis: antagonization of IFN‐β mediated suppression of MMPs

Neutralizing antibodies (NAb) against interferon‐β (IFN‐β) develop in about a third of treated multiple sclerosis patients and are believed to reduce therapeutic efficacy of IFN‐β on clinical and MRI measures. The expression of the interferon acute‐response protein, myxovirus resistance protein A (MxA) is a sensitive measure of the biological activity of therapeutically applied IFN‐β and of its reduced bioavailability due to NAb. However, MxA may not be operative in the pathogenesis of multiple sclerosis or the therapeutic effect of IFN‐β. Instead, matrix metalloproteinases (MMPs) are increased in brain tissue, CSF and blood circulation of multiple sclerosis patients and function as effector molecules in several steps of multiple sclerosis pathogenesis. One of the molecular mechanisms by which IFN‐β exerts its beneficial effect in multiple sclerosis is reduction of MMP‐9 expression and increase of its endogenous tissue inhibitor, TIMP‐1. Quantitative PCR measurements of MMP‐2 and MMP‐9, TIMP‐1 and TIMP‐2, and MxA were performed in peripheral mononuclear cells from clinically stable multiple sclerosis patients with relapsing remitting disease course after short‐term and long‐term treatment with IFN‐β. IFN‐β therapy down‐regulated the expression of MMP‐9 and abolished that of MMP‐2 in long‐term, but not short‐term treated multiple sclerosis, while levels of MxA were increased in both instances. The presence of NAb reversed these effects, i.e. led to reduced MxA and increased MMP‐2/MMP‐9 expression levels compared with NAb- patients. In contrast, expression of TIMPs in peripheral blood mononuclear cells remained unaffected by IFN‐β therapy and the presence of NAb. While MxA is able to detect the biological action and reduced bioavailability of IFN‐β on the basis of single injections, only MMP‐9 shows quantitative correlation with the NAb titre. Together with evidence that an imbalance between MMP and TIMP expression is a crucial pathogenetic feature in multiple sclerosis, these findings support the concept of a significant role of NAb in reducing the therapeutic efficacy of IFN‐

Assessment of brain cancer atlas maps with multimodal imaging features.

BACKGROUND: Glioblastoma Multiforme (GBM) is a fast-growing and highly aggressive brain tumor that invades the nearby brain tissue and presents secondary nodular lesions across the whole brain but generally does not spread to distant organs. Without treatment, GBM can result in death in about 6 months. The challenges are known to depend on multiple factors: brain localization, resistance to conventional therapy, disrupted tumor blood supply inhibiting effective drug delivery, complications from peritumoral edema, intracranial hypertension, seizures, and neurotoxicity. MAIN TEXT: Imaging techniques are routinely used to obtain accurate detections of lesions that localize brain tumors. Especially magnetic resonance imaging (MRI) delivers multimodal images both before and after the administration of contrast, which results in displaying enhancement and describing physiological features as hemodynamic processes. This review considers one possible extension of the use of radiomics in GBM studies, one that recalibrates the analysis of targeted segmentations to the whole organ scale. After identifying critical areas of research, the focus is on illustrating the potential utility of an integrated approach with multimodal imaging, radiomic data processing and brain atlases as the main components. The templates associated with the outcome of straightforward analyses represent promising inference tools able to spatio-temporally inform on the GBM evolution while being generalizable also to other cancers. CONCLUSIONS: The focus on novel inference strategies applicable to complex cancer systems and based on building radiomic models from multimodal imaging data can be well supported by machine learning and other computational tools potentially able to translate suitably processed information into more accurate patient stratifications and evaluations of treatment efficacy

The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

The activation of peroxisome proliferator activated receptros (PPARs) as the regulator of lipid metabolism in the placenta of patients with diabetes

Dadas las alteraciones metabólicas inducidas por la diabetes materna y la capacidad de los receptores nucleares PPAR de regular el metabolismo lipídico, se propuso como objetivo evaluar los niveles de lípidos y PPAR en la placenta de pacientes sanas y con diabetes tipo 2, y determinar si la activación de los PPAR regula los niveles y peroxidación lipídica en dichos tejidos. Metodología: las placentas se obtuvieron luego del alumbramiento, se determinaron los niveles de lípidos mediante cromatografía, los niveles de PPAR mediante Western blot y la peroxidación lipídica mediante la cuantificación de TBARS. Resultados: se evidenciaron mayores niveles de lípidos y menores niveles de PPAR_ y PPARaen placenta de pacientes diabéticas en relación con el control (P<0,05). Los agonistas de PPAR_ redujeron la masa lipídica en la placenta de pacientes sanas y diabéticas, mientras que la activación de PPARb la redujo sólo en la placenta de pacientes sanas. Al activar PPARaaumenta la masa lipídica y la expresión de la enzima de síntesis de ácidos grasos FASN (P<0,05). La peroxidación lipídica, incrementada en placenta de pacientes diabéticas (P<0,001), se reguló negativamente al activar los tres isotipos de los PPAR (P<0,05). Conclusión: se identificaron en este estudio noveles funciones de los PPAR en la placenta humana, relevantes en la regulación del metabolismo lipídico y la lipoperoxidación. La diabetes tipo 2 induce a nivel placentario alteraciones en los niveles y función de los PPAR vinculadas a las importantes anomalías en el metabolismo lipídico y un estado prooxidante inducidas por esta patología.Due to the metabolic alterations induced by maternal diabetes and the capacity of nuclear receptors PPARs to regulate lipid metabolism the aim of this study was to evaluate the concentrations of lipids and PPARs in the placenta from healthy and type 2 diabetic patients and to determine whether PPARs activation regulate lipid concentrations and peroxidation in these tissues. Methods: Placentas were obtained after delivery, lipid levels were determined by chromatography, concentrations of PPARs isotypes were evaluated by Western blot and the lipid peroxidation determined by TBARS quantification. Results: There are higher levels of lipids and lower concentrations of PPAR_ and PPARa in the placenta from diabetic patients when compared to controls (P<0.05). PPAR_ agonists decreased the lipid mass in the placenta from healthy and diabetic patients, while PPARb activation decreased the lipid mass only in the placenta from healthy patients. When PPARa was activated, the lipid mass and the expression of the fatty acid synthase enzyme (FASN) were increased. Lipid peroxidation, increased in the placenta from diabetic patients (P<0.001), was negatively regulated when the three PPARs were activated (P<0.05). Conclusion: We identified in this work novel PPAR functions in the human placenta as relevant regulators of lipid metabolism and peroxidation. Type 2 diabetes induced in the placenta alterations in PPARs expression and function, related to the important anomalies in lipid metabolism and the pro-oxidative state induced by this pathology.Fil: Capobianco, Evangelina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Martinez, Nora Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Fornes, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Higa, Romina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Kurtz, Melisa Lidia Amelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Di Marco, Ingrid. Hospital Materno-Infantil Ramón Sardá; ArgentinaFil: Basualdo, María Natalia. Hospital Materno-Infantil Ramón Sardá; ArgentinaFil: Faingold, Cristina. Hospital César Milstein; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin