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)

Regulation of G protein-coupled receptor kinase subtypes by calcium sensor proteins

AbstractG protein-coupled receptor homologous desensitization is intrinsically related to the function of a class of S/T kinases named G protein-coupled receptor kinases (GRK). The GRK family is composed of six cloned members, named GRK1 to 6. Studies from different laboratories have demonstrated that different calcium sensor proteins (CSP) can selectively regulate the activity of GRK subtypes. In the presence of calcium, rhodopsin kinase (GRK1) is inhibited by the photoreceptor-specific CSP recoverin through direct binding. Several other recoverin homologues (including NCS 1, VILIP 1 and hippocalcin) are also able to inhibit GRK1. The ubiquitous calcium-binding protein calmodulin (CaM) can inhibit GRK5 with a high affinity (IC50=40–50 nM). A direct interaction between GRK5 and Ca2+/CaM was documented and this binding does not influence the catalytic activity of the kinase, but rather reduced GRK5 binding to the membrane. These studies suggest that CSP act as functional analogues in mediating the regulation of different GRK subtypes by Ca2+. This mechanism is, however, highly selective with respect to the GRK subtypes: while GRK1, but not GRK2 and GRK5, is regulated by recoverin and other NCS, GRK4, 5 and 6, that belong to the GRK4 subfamily, are potently inhibited by CaM, which had little or no effect on members of other GRK subfamilies

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

Metabolomics in Otorhinolaryngology

Otorhinolaryngology (Ear, Nose and Throat-ENT) focuses on inflammatory, immunological, infectious, and neoplastic disorders of the head and neck and on their medical and surgical therapy. The fields of interest of this discipline are the ear, the nose and its paranasal sinuses, the oral cavity, the pharynx, the larynx, and the neck. Besides surgery, there are many other diagnostic aspects of ENT such as audiology and Vestibology, laryngology, phoniatrics, and rhinology. A new advanced technology, named metabolomics, is significantly impacting the field of ENT. All the “omics” sciences, such as genomics, transcriptomics, and proteomics, converge at the level of metabolomics, which is considered the integration of all “omics.” Its application will change the way several of ENT disorders are diagnosed and treated. This review highlights the power of metabolomics, including its pitfalls and promise, and several of its most relevant applications in ENT to provide a basic understanding of the metabolites associated with these districts. In particular, the attention has been focused on different heterogeneous diseases, from head and neck cancer to allergic rhinitis, hearing loss, obstructive sleep apnea, noise trauma, sinusitis, and Meniere’s disease. In conclusion, metabolomics study indicates a “fil rouge” that links these pathologies to improve three aspects of patient care: diagnostics, prognostics, and therapeutics, which in one word is defined as precision medicine

Modeling of enhanced field confinement and scattering by optical wire antennas.

We describe the application of full-wave and semi-analytical numerical tools for the modeling of optical wire antennas, with the aim of providing novel guidelines for analysis and design. The concept of antenna impedance at optical frequencies is reviewed by means of finite-element simulations, whereas a surface-impedance integral equation is derived in order to perform an accurate and efficient calculation of the current distribution, and thereby to determine the equivalent-circuit parameters. These are introduced into simple circuits models, directly borrowed from radio frequency, which are applied in order to model the phenomena of enhanced field confinement at the feed gap and light scattering by optical antennas illuminated by plane waves

Platinated Nucleotides are Substrates for the Human Mitochondrial Deoxynucleotide Carrier (DNC) and DNA Polymerase g: Relevance for the Development of New Platinum-Based Drugs.

cis-[PtCl2(NH3)2] (cisplatin) is among the highest effective antitumor drugs used for the chemotherapeutic treatment of a broad range of malignancies. Recently, alongside with the classical direct bond to DNA, an alternative mechanism of action mediated by N7 platinated nucleotides has been suggested for cisplatin. Considering that mitochondria play an important role in cell death activation and in a significant portion of the clinical activity and pharmacological properties associated with cisplatin, aim of this research was to evaluate the possibility that platinated deoxynucleotides, as the model complex [Pt(dien)(N7-5’-dGTP)] (1), dien=diethylenetriamine, could be transported into mitochondria and then incorporated into mtDNA. The kinetic characterization has revealed that the mitochondrial deoxynucleotide carrier (DNC) transports complex 1 with high affinity. Finally, a highly efficient in organello DNA synthesis system, followed by ICP-AES, has demonstrated that [Pt(dien)(N7-5’-dGTP)] is incorporated in the mitochondrial DNA by DNA polymerase g. These results may have critical implications in the development of new generations of anticancer and/or antiviral nucleotide analogues with more specific cellular targets and fewer side effects

Role of G Protein-coupled Receptor Kinase 4 and β-Arrestin 1 in Agonist-stimulated Metabotropic Glutamate Receptor 1 Internalization and Activation of Mitogen-activated Protein Kinases

The metabotropic glutamate 1 (mGlu(1)) receptor in cerebellar Purkinje cells plays a key role in motor learning and motor coordination. Here we show that the G protein-coupled receptor kinases (GRK) 2 and 4, which are expressed in these cells, regulate the mGlu(1) receptor by at least in part different mechanisms. Using kinase-dead mutants in HEK293 cells, we found that GRK4, but not GRK2, needs the intact kinase activity to desensitize the mGlu(1) receptor, whereas GRK2, but not GRK4, can interact with and regulate directly the activated Galpha(q). In cells transfected with GRK4 and exposed to agonist, beta-arrestin was first recruited to plasma membranes, where it was co-localized with the mGlu(1) receptor, and then internalized in vesicles. The receptor was also internalized but in different vesicles. The expression of beta-arrestin V53D dominant negative mutant, which did not affect the mGlu(1) receptor internalization, reduced by 70-80% the stimulation of mitogen-activated protein (MAP) kinase activation by the mGlu(1) receptor. The agonist-stimulated differential sorting of the mGlu(1) receptor and beta-arrestin as well as the activation of MAP kinases by mGlu(1) agonist was confirmed in cultured cerebellar Purkinje cells. A major involvement of GRK4 and of beta-arrestin in agonist-dependent receptor internalization and MAP kinase activation, respectively, was documented in cerebellar Purkinje cells using an antisense treatment to knock down GRK4 and expressing beta-arrestin V53D dominant negative mutant by an adenovirus vector. We conclude that GRK2 and GRK4 regulate the mGlu(1) receptor by different mechanisms and that beta-arrestin is directly involved in glutamate-stimulated MAP kinase activation by acting as a signaling molecule

JAK3/STAT5/6 Pathway Alterations Are Associated with Immune Deviation in CD8+ T Cells in Renal Cell Carcinoma Patients

To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8+ T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8+ T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8+ T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle, was observed. These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8+ effector cells. If validated, this may define a therapeutic target in the setting of patients with RCC

6G White Paper on Machine Learning in Wireless Communication Networks

The focus of this white paper is on machine learning (ML) in wireless communications. 6G wireless communication networks will be the backbone of the digital transformation of societies by providing ubiquitous, reliable, and near-instant wireless connectivity for humans and machines. Recent advances in ML research has led enable a wide range of novel technologies such as self-driving vehicles and voice assistants. Such innovation is possible as a result of the availability of advanced ML models, large datasets, and high computational power. On the other hand, the ever-increasing demand for connectivity will require a lot of innovation in 6G wireless networks, and ML tools will play a major role in solving problems in the wireless domain. In this paper, we provide an overview of the vision of how ML will impact the wireless communication systems. We first give an overview of the ML methods that have the highest potential to be used in wireless networks. Then, we discuss the problems that can be solved by using ML in various layers of the network such as the physical layer, medium access layer, and application layer. Zero-touch optimization of wireless networks using ML is another interesting aspect that is discussed in this paper. Finally, at the end of each section, important research questions that the section aims to answer are presented