Dependencies and Simultaneity in Membrane Systems

Membrane system computations proceed in a synchronous fashion: at each step all the applicable rules are actually applied. Hence each step depends on the previous one. This coarse view can be refined by looking at the dependencies among rule occurrences, by recording, for an object, which was the a rule that produced it and subsequently (in a later step), which was the a rule that consumed it. In this paper we propose a way to look also at the other main ingredient in membrane system computations, namely the simultaneity in the rule applications. This is achieved using zero-safe nets that allows to synchronize transitions, i.e., rule occurrences. Zero-safe nets can be unfolded into occurrence nets in a classical way, and to this unfolding an event structure can be associated. The capability of capturing simultaneity of zero-safe nets is transferred on the level of event structure by adding a way to express which events occur simultaneously

Development of a human model for the study of effects of hypoxia, exercise, and sildenafil on cardiac and vascular function in chronic heart failure

Background: Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. Methods and Results: In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (−1 ± 2%; P = 0.043), systemic vascular resistance (−87 ± 156 dyn·s−1·cm−2; P = 0.034), and RVTG (−2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P < 0.001) and RVTG (19 ± 11 mm Hg; P < 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil. Conclusions: Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation–perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension

L’e-WOM come Strumento di Gestione nel Settore Alberghiero Italiano

The tourism industry has been significantly influenced by the development of Information and Communication Technologies (Icts), among them the electronic Word-Of-Mouth (e-Wom) plays an important role allowing users to provide online opinions about their experience as tourists. Hotels are the tour operators most concerned by this application from which they can get feedback and exploit the information generated to improve management and results. This research, through an empirical study from which 136 questionnaires completed by Italian hotel owners and directors were obtained, aims to add value through the study of the e-Wom as a managerial tool, deepening the perspective of hotel managers regarding this application. The analysis of the results shows differences based on the interviewee's profile and the hotel characteristics that allow interesting considerations on the topic

El Boca-oído Online como Herramienta para la Gestión Hotelera. El Estado de la Cuestión

La industria turística se ha visto notablemente afectada por el desarrollo de las tecnologías de la información como la comunicación boca-oído electrónico o e-WOM, que permite a los usuarios ofrecer opinión online sobre su experiencia como turistas. Los hoteles son muy afectados por la aplicación, de la que pueden obtener retroalimentación y aprovechar la información generada para mejorar su gestión y resultados. Hasta el momento, la literatura académica sobre el tema se ha centrado en la perspectiva del consumidor y ha prestado escasa atención a la gestión. Esta investigación pretende añadir valor mediante el estudio del estado de la cuestión del e-WOM como herramienta para la gestión, centrándose en hoteles del ámbito español. Se realiza un análisis descriptivo de la situación desde una encuesta dirigida a directivos hoteleros, que permite distinguir entre usuarios y no usuarios del sistema. Los resultados indican la no existencia de diferencias entre ambos grupos por características del encuestado, ni por sus percepciones sobre las ventajas de la aplicación; las diferencias emergen al considerar fiabilidad y reflejo de la realidad, así como intenciones de uso futuro de la herramienta

Aspects of multiscale modelling in a process algebra for biological systems

We propose a variant of the CCS process algebra with new features aiming at allowing multiscale modelling of biological systems. In the usual semantics of process algebras for modelling biological systems actions are instantaneous. When different scale levels of biological systems are considered in a single model, one should take into account that actions at a level may take much more time than actions at a lower level. Moreover, it might happen that while a component is involved in one long lasting high level action, it is involved also in several faster lower level actions. Hence, we propose a process algebra with operations and with a semantics aimed at dealing with these aspects of multiscale modelling. We study behavioural equivalences for such an algebra and give some examples

A Process Calculus for Molecular Interaction Maps

We present the MIM calculus, a modeling formalism with a strong biological basis, which provides biologically-meaningful operators for representing the interaction capabilities of molecular species. The operators of the calculus are inspired by the reaction symbols used in Molecular Interaction Maps (MIMs), a diagrammatic notation used by biologists. Models of the calculus can be easily derived from MIM diagrams, for which an unambiguous and executable interpretation is thus obtained. We give a formal definition of the syntax and semantics of the MIM calculus, and we study properties of the formalism. A case study is also presented to show the use of the calculus for modeling biomolecular networks.Comment: 15 pages; 8 figures; To be published on EPTCS, proceedings of MeCBIC 200

Immunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients

Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments.Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments

Search for Third Generation Vector Leptoquarks in p anti-p Collisions at sqrt(s) = 1.96 TeV

We describe a search for a third generation vector leptoquark (VLQ3) that decays to a b quark and tau lepton using the CDF II detector and 322 pb^(-1) of integrated luminosity from the Fermilab Tevatron. Vector leptoquarks have been proposed in many extensions of the standard model (SM). Observing a number of events in agreement with SM expectations, assuming Yang-Mills (minimal) couplings, we obtain the most stringent upper limit on the VLQ3 pair production cross section of 344 fb (493 fb) and lower limit on the VLQ3 mass of 317 GeV/c^2 (251 GeV/c^2) at 95% C.L.Comment: 7 pages, 2 figures, submitted to PR

B-type natriuretic peptide-induced delayed modulation of TRPV1 and P2X3 receptors of mouse trigeminal sensory neurons

Important pain transducers of noxious stimuli are small- and medium-diameter sensory neurons that express transient receptor vanilloid-1 (TRPV1) channels and/or adenosine triphosphate (ATP)-gated P2X3 receptors whose activity is upregulated by endogenous neuropeptides in acute and chronic pain models. Little is known about the role of endogenous modulators in restraining the expression and function of TRPV1 and P2X3 receptors. In dorsal root ganglia, evidence supports the involvement of the natriuretic peptide system in the modulation of nociceptive transmission especially via the B-type natriuretic peptide (BNP) that activates the natriuretic peptide receptor-A (NPR-A) to downregulate sensory neuron excitability. Since the role of BNP in trigeminal ganglia (TG) is unclear, we investigated the expression of BNP in mouse TG in situ or in primary cultures and its effect on P2X3 and TRPV1 receptors of patch-clamped cultured neurons. Against scant expression of BNP, almost all neurons expressed NPRA at membrane level. While BNP rapidly increased cGMP production and Akt kinase phosphorylation, there was no early change in passive neuronal properties or responses to capsaicin, \u3b1,\u3b2-meATP or GABA. Nonetheless, 24 h application of BNP depressed TRPV1 mediated currents (an effect blocked by the NPR-A antagonist anantin) without changing responses to \u3b1,\u3b2-meATP or GABA. Anantin alone decreased basal cGMP production and enhanced control \u3b1,\u3b2-meATP-evoked responses, implying constitutive regulation of P2X3 receptors by ambient BNP. These data suggest a slow modulatory action by BNP on TRPV1 and P2X3 receptors outlining the role of this peptide as a negative regulator of trigeminal sensory neuron excitability to nociceptive stimuli. \ua9 2013 Vilotti et al