Theorem proving for non-normal modal logics

In this work we briefly summarize our recent contributions in the field of proof methods, theorem proving and countermodel generation for non-normal modal logics. We first recall some labelled sequent calculi for the basic system E and its extensions with axioms M, N, and C based on bi-neighbourhood semantics. Then, we present PRONOM, a theorem prover and countermodel generator for non-normal modal logics implemented in Prolog. When a modal formula is valid, then PRONOM computes a proof in the labelled calculi, otherwise it is able to extract a model falsifying it from an open, saturated branch. © 2020 for this paper by its authors. Use permitted under Creative Commons License Attribution 4.0 International (CC BY 4.0).Peer reviewe

A compact light readout system for longitudinally segmented shashlik calorimeters

The longitudinal segmentation of shashlik calorimeters is challenged by dead zones and non-uniformities introduced by the light collection and readout system. This limitation can be overcome by direct fiber-photosensor coupling, avoiding routing and bundling of the wavelength shifter fibers and embedding ultra-compact photosensors (SiPMs) in the bulk of the calorimeter. We present the first experimental test of this readout scheme performed at the CERN PS-T9 beamline in 2015 with negative particles in the 1-5~GeV energy range. In this paper, we demonstrate that the scheme does not compromise the energy resolution and linearity compared with standard light collection and readout systems. In addition, we study the performance of the calorimeter for partially contained charged hadrons to assess the $e/\pi$ separation capability and the response of the photosensors to direct ionization.Comment: To appear in Nuclear Instruments and Methods in Physics Research,

Generic Modal Cut Elimination Applied to Conditional Logics

We develop a general criterion for cut elimination in sequent calculi for propositional modal logics, which rests on absorption of cut, contraction, weakening and inversion by the purely modal part of the rule system. Our criterion applies also to a wide variety of logics outside the realm of normal modal logic. We give extensive example instantiations of our framework to various conditional logics. For these, we obtain fully internalised calculi which are substantially simpler than those known in the literature, along with leaner proofs of cut elimination and complexity. In one case, conditional logic with modus ponens and conditional excluded middle, cut elimination and complexity were explicitly stated as open in the literature

A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles

Current approaches for the treatment of chronic lymphocytic leukemia (CLL) have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term sideeffects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant cells. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanoparticles coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated/deleted leukemia cells expressing a low amount of CD20, but also circulating primary cells isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders. [Figure not available: see fulltext.

Long-term effects of the new direct antiviral agents (DAAs) therapy for HCV-related mixed cryoglobulinaemia without renal involvement: a multicentre open-label study

Objective. To investigate the long-term effects and safety of new direct antiviral agents (DAAs) in patients with hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC) without renal involvement.Methods. The study enrolled 22 consecutive patients, 19 received sofosbuvir-based regimen and three patients received other DAAs, individually tailored according to latest guidelines. As of December 2016, the median length of follow-up was 17 months (range 13-21).Results. Extra-hepatic manifestations at enrollment were: purpura and arthralgia (12 cases), peripheral neuropathy (10 cases) and marginal zone Blymphomas (2 cases). After a four-week DAA therapy, all patients became HCV-negative. Moreover, after 48 weeks since the beginning of DAA treatment, sustained regression of purpura and arthralgias was observed respectively in eight and in nine cases; peripheral neuropathy improved in seven cases, and cryocrit median values decreased from three (1-20) at baseline to two (1-12) after 48 weeks. Two cases with indolent marginal zone lymphomas did not show any haematological response: size and number of the involved nodes remained unchanged. In addition, the monoclonal B-cell population found in the peripheral blood in four cases did not disappear after recovery from HCV-RNA. Mild side effects occurred in nine patients, but six patients developed ribavirin-related anaemia requiring reduction of ribavirin dose.Conclusion. DAA therapy is safe and effective to eradicate HCV in MC, but seems associated with satisfactory clinical response in mild or moderate cryoglobulinaemic vasculitis and no response in B-NHL

Prospect for Charge Current Neutrino Interactions Measurements at the CERN-PS

Tensions in several phenomenological models grew with experimental results on neutrino/antineutrino oscillations at Short-Baseline (SBL) and with the recent, carefully recomputed, antineutrino fluxes from nuclear reactors. At a refurbished SBL CERN-PS facility an experiment aimed to address the open issues has been proposed [1], based on the technology of imaging in ultra-pure cryogenic Liquid Argon (LAr). Motivated by this scenario a detailed study of the physics case was performed. We tackled specific physics models and we optimized the neutrino beam through a full simulation. Experimental aspects not fully covered by the LAr detection, i.e. the measurements of the lepton charge on event-by-event basis and their energy over a wide range, were also investigated. Indeed the muon leptons from Charged Current (CC) (anti-)neutrino interactions play an important role in disentangling different phenomenological scenarios provided their charge state is determined. Also, the study of muon appearance/disappearance can benefit of the large statistics of CC muon events from the primary neutrino beam. Results of our study are reported in detail in this proposal. We aim to design, construct and install two Spectrometers at "NEAR" and "FAR" sites of the SBL CERN-PS, compatible with the already proposed LAr detectors. Profiting of the large mass of the two Spectrometers their stand-alone performances have also been exploited.Comment: 70 pages, 38 figures. Proposal submitted to SPS-C, CER

Updates in Rhea - an expert curated resource of biochemical reactions.

Rhea (http://www.rhea-db.org) is a comprehensive and non-redundant resource of expert-curated biochemical reactions designed for the functional annotation of enzymes and the description of metabolic networks. Rhea describes enzyme-catalyzed reactions covering the IUBMB Enzyme Nomenclature list as well as additional reactions, including spontaneously occurring reactions, using entities from the ChEBI (Chemical Entities of Biological Interest) ontology of small molecules. Here we describe developments in Rhea since our last report in the database issue of Nucleic Acids Research. These include the first implementation of a simple hierarchical classification of reactions, improved coverage of the IUBMB Enzyme Nomenclature list and additional reactions through continuing expert curation, and the development of a new website to serve this improved dataset

Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: A multicenter randomised controlled clinical trial

Objectives: Coupled plasma filtration adsorption (CPFA, Bellco, Italy), to remove inflammatory mediators from blood, has been proposed as a novel treatment for septic shock. This multicenter, randomised, nonblinded trial compared CPFA with standard care in the treatment of critically ill patients with septic shock. Design: Prospective, multicenter, randomised, openlabel, two parallel group and superiority clinical trial. Setting: 18 Italian adult, general, intensive care units (ICUs). Participants: Of the planned 330 adult patients with septic shock, 192 were randomised to either have CPFA added to the standard care, or not. The external monitoring committee excluded eight ineligible patients who were erroneously included. Interventions: CPFA was to be performed daily for 5 days, lasting at least 10 h/day. Primary and secondary outcome measures: The primary endpoint was mortality at discharge from the hospital at which the patient last stayed. Secondary endpoints were: 90-day mortality, new organ failures and ICU-free days within 30 days. Results: There was no statistical difference in hospital mortality (47.3% controls, 45.1% CPFA; p=0.76), nor in secondary endpoints, namely the occurrence of new organ failures (55.9% vs 56.0%; p=0.99) or free-ICU days during the first 30 days (6.8 vs 7.5; p=0.35). The study was terminated on the grounds of futility. Several patients randomised to CPFA were subsequently found to be undertreated. An a priori planned subgroup analysis showed those receiving a CPFA dose >0.18 L/kg/day had a lower mortality compared with controls (OR 0.36, 95% CI 0.13 to 0.99). Conclusions: CPFA did not reduce mortality in patients with septic shock, nor did it positively affect other important clinical outcomes. A subgroup analysis suggested that CPFA could reduce mortality, when a high volume of plasma is treated. Owing to the inherent potential biases of such a subgroup analysis, this result can only be viewed as a hypothesis generator and should be confirmed in future studies