Interaction systems I : the theory of optimal reductions

Projet PARAA new class of higher order rewriting systems, called interaction systems is introduced. From one side, interaction systems provide the intuitionistic generalization of Lafont's interaction nets (recall that interaction nets are linear). In particular, we keep the idea of binary interaction and the syntactical bipartition of operators into constructors and destructors. From the other side, interaction systems are the subsystem of Klop's combinatory reduction systems where the Curry-Howard analogy stoll "makes sense". This means that we can associate with every IS a suitable logical (intuitionistic) system ; constructors and destructors respectively correspond to right and left introduction rules, interaction is cut and computation is cut-elimination. Interaction systems have been primarily motivated by the necessity of extending Lamping's optimal graph reduction technique for the l-calculus to other computational constructs than just -reduction. This implementation style can be smootly generalized to arbitrary IS's providing in this way a uniform description of essential rules such as conditionals and recursion The optimal implementation of IS's will be only sketched here (it will eventually be the subject of the forthcoming Part II). The main aim of this paper is to introduce this new class of systems, to discuss the motivations behind its definition and to investigate the theoretical aspect of optimal reductions (in particular, the notion of redex-family)

ALS mutant FUS proteins are recruited into stress granules in induced pluripotent stem cells- derived motoneurons

Patient-derived induced Pluripotent Stem Cells (iPSCs) provide an opportunity to study human diseases mainly in those cases where no suitable model systems are available. Here we have taken advantage of in vitro iPSCs derived from patients affected by Amyotrophic Lateral Sclerosis and carrying mutations in the RNA-binding proteins FUS to study the cellular behavior of the mutant proteins in the appropriate genetic background. Moreover, the ability to differentiate iPSCs into spinal cord neural cells provides an in vitro model mimicking the physiological conditions. iPSCs were derived from FUS(R514S) and FUS(R521C) patients' fibroblasts, while in the case of the severe FUS(P525L) mutation, where fibroblasts were not available, a heterozygous and a homozygous iPSC lines were raised by TALEN-directed mutagenesis. We show that aberrant localization and recruitment of FUS into stress granules (SGs) is a prerogative of the FUS mutant proteins and occurs only upon induction of stress in both undifferentiated iPSCs and spinal cord neural cells. Moreover, we show that the incorporation into SGs is proportional to the amount of cytoplasmic FUS, nicely correlating with the cytoplasmic delocalization phenotype of the different mutants. Therefore, the available iPSCs represent a very powerful system for understanding the correlation between FUS mutations, the molecular mechanisms of SG formation and ALS ethiopathogenesis

Transient subdiffusion via disordered quantum walks

Transport phenomena play a crucial role in modern physics and applied sciences. Examples include thedissipation of energy across a large system, the distribution of quantum information in optical networks, andthe timely modeling of spreading diseases. In this work we experimentally prove the feasibility of disorderedquantum walks to realize a quantum simulator that is able to model general transient subdiffusive phenomena,exhibiting a sublinear spreading in space over time. Our experiment simulates such phenomena by means ofa finely controlled insertion of various levels of disorder during the evolution of the walker, enabled by theunique flexibility of our setup. This allows us to explore the full range of subdiffusive behaviors, ranging fromanomalous Anderson-like localization to normal diffusion for all experimentally accessible step numbers

The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity

Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup. Mechanistically, linc-NeD125 is able to recruit the miRNA-induced silencing complex (miRISC) and to directly bind the microRNAs miR-19a-3p, miR-19b-3p and miR-106a-5p. Functionally, linc-NeD125 acts as a competing endogenous RNA (ceRNA) that, sequestering the three miRNAs, leads to de-repression of their targets CDK6, MYCN, SNCAIP, and KDM6A, which are major driver genes of G4 MB. Accordingly, linc-NeD125 downregulation reduces G4 cell proliferation. Moreover, we also provide evidence that linc-NeD125 ectopic expression in the aggressive Group 3 MB cells attenuates their proliferation, migration and invasion. This study unveils the first lncRNA-based ceRNA network in central nervous system tumours and provides a novel molecular circuit underlying the enigmatic Group 4 medulloblastoma

Direct Anterior versus Lateral Approach for Femoral Neck Fracture: Role in COVID-19 Disease

Background: During the COVID-19 emergency, the incidence of fragility fractures in elderly patients remained unchanged. The management of these patients requires a multidisciplinary approach. The study aimed to assess the best surgical approach to treat COVID-19 patients with femoral neck fracture undergoing hemiarthroplasty (HA), comparing direct lateral (DL) versus direct anterior approach (DAA). Methods: A single-center, observational retrospective study including 50 patients affected by COVID-19 infection (30 males, 20 females) who underwent HA between April 2020 to April 2021 was performed. The patients were allocated into two groups according to the surgical approach used: lateral approach and anterior approach. For each patient, the data were recorded: age, sex, BMI, comorbidity, oxygen saturation (SpO2), fraction of the inspired oxygen (FiO2), type of ventilation invasive or non-invasive, HHb, P/F ratio (PaO2/FiO2), hemoglobin level the day of surgery and 1 day post operative, surgical time, Nottingham Hip Fractures Score (NHFS) and American Society of Anesthesiologists Score (ASA). The patients were observed from one hour before surgery until 48 h post-surgery of follow-up. The patients were stratified into five groups according to Alhazzani scores. A non-COVID-19 group of patients, as the control, was finally introduced. Results: A lateral position led to a better level of oxygenation (p < 0.01), compared to the supine anterior approach. We observed a better post-operative P/F ratio and a reduced need for invasive ventilation in patients lying in the lateral position. A statistically significant reduction in the surgical time emerged in patients treated with DAA (p < 0.01). Patients within the DAA group had a significantly lower blood loss compared to direct lateral approach. Conclusions: DL approach with lateral decubitus seems to preserved respiratory function in HA surgery. Thus, the lateral position may be associated with beneficial effects on gas exchange

Electromagnetic Design of Microwave Cavities for Side-Coupled Linear Accelerators: A Hybrid Numerical/Analytical Approach

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Design of Electromagnetic Bandgap Cavities for High-Gradient On-Axis Coupled-Cavity Linear Accelerators

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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

Paths, Computations and Labels in the λ-calculus

We provide a new characterization of Levy's redex-families in the - calculus [12] as suitable paths in the initial term of the derivation. The idea is that redexes in a same family are created by "contraction" (via fi-reduction) of a unique common path in the initial term. This fact gives new evidence about the "common nature" of redexes in a same family, and about the possibility of sharing their reduction. In general, paths seem to provide a very friendly and intuitive tool for reasoning about redex-families, as well in theory (using paths, we shall provide a remarkably simple proof of the equivalence between extraction [12] and labeling) as in practice (our characterization underlies all recent works on optimal graph reduction techniques for the λ-calculus [10, 7, 8, 1], providing an original and intuitive understanding of optimal implementations). Finally, as an easy by-product of the path-characterization, we prove that neither overlining nor underlining are required in Levy's ..