Structural Basis for Feed-Forward Transcriptional Regulation of Membrane Lipid Homeostasis in Staphylococcus aureus

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Invariant-free deduction systems for temporal logic

In this thesis we propose a new approach to deduction methods for temporal logic. Our proposal is based on an inductive definition of eventualities that is different from the usual one. On the basis of this non-customary inductive definition for eventualities, we first provide dual systems of tableaux and sequents for Propositional Linear-time Temporal Logic (PLTL). Then, we adapt the deductive approach introduced by means of these dual tableau and sequent systems to the resolution framework and we present a clausal temporal resolution method for PLTL. Finally, we make use of this new clausal temporal resolution method for establishing logical foundations for declarative temporal logic programming languages. The key element in the deduction systems for temporal logic is to deal with eventualities and hidden invariants that may prevent the fulfillment of eventualities. Different ways of addressing this issue can be found in the works on deduction systems for temporal logic. Traditional tableau systems for temporal logic generate an auxiliary graph in a first pass.Then, in a second pass, unsatisfiable nodes are pruned. In particular, the second pass must check whether the eventualities are fulfilled. The one-pass tableau calculus introduced by S. Schwendimann requires an additional handling of information in order to detect cyclic branches that contain unfulfilled eventualities. Regarding traditional sequent calculi for temporal logic, the issue of eventualities and hidden invariants is tackled by making use of a kind of inference rules (mainly, invariant-based rules or infinitary rules) that complicates their automation. A remarkable consequence of using either a two-pass approach based on auxiliary graphs or aone-pass approach that requires an additional handling of information in the tableau framework, and either invariant-based rules or infinitary rules in the sequent framework, is that temporal logic fails to carry out the classical correspondence between tableaux and sequents. In this thesis, we first provide a one-pass tableau method TTM that instead of a graph obtains a cyclic tree to decide whether a set of PLTL-formulas is satisfiable. In TTM tableaux are classical-like. For unsatisfiable sets of formulas, TTM produces tableaux whose leaves contain a formula and its negation. In the case of satisfiable sets of formulas, TTM builds tableaux where each fully expanded open branch characterizes a collection of models for the set of formulas in the root. The tableau method TTM is complete and yields a decision procedure for PLTL. This tableau method is directly associated to a one-sided sequent calculus called TTC. Since TTM is free from all the structural rules that hinder the mechanization of deduction, e.g. weakening and contraction, then the resulting sequent calculus TTC is also free from this kind of structural rules. In particular, TTC is free of any kind of cut, including invariant-based cut. From the deduction system TTC, we obtain a two-sided sequent calculus GTC that preserves all these good freeness properties and is finitary, sound and complete for PLTL. Therefore, we show that the classical correspondence between tableaux and sequent calculi can be extended to temporal logic. The most fruitful approach in the literature on resolution methods for temporal logic, which was started with the seminal paper of M. Fisher, deals with PLTL and requires to generate invariants for performing resolution on eventualities. In this thesis, we present a new approach to resolution for PLTL. The main novelty of our approach is that we do not generate invariants for performing resolution on eventualities. Our method is based on the dual methods of tableaux and sequents for PLTL mentioned above. Our resolution method involves translation into a clausal normal form that is a direct extension of classical CNF. We first show that any PLTL-formula can be transformed into this clausal normal form. Then, we present our temporal resolution method, called TRS-resolution, that extends classical propositional resolution. Finally, we prove that TRS-resolution is sound and complete. In fact, it finishes for any input formula deciding its satisfiability, hence it gives rise to a new decision procedure for PLTL. In the field of temporal logic programming, the declarative proposals that provide a completeness result do not allow eventualities, whereas the proposals that follow the imperative future approach either restrict the use of eventualities or deal with them by calculating an upper bound based on the small model property for PLTL. In the latter, when the length of a derivation reaches the upper bound, the derivation is given up and backtracking is used to try another possible derivation. In this thesis we present a declarative propositional temporal logic programming language, called TeDiLog, that is a combination of the temporal and disjunctive paradigms in Logic Programming. We establish the logical foundations of our proposal by formally defining operational and logical semantics for TeDiLog and by proving their equivalence. Since TeDiLog is, syntactically, a sublanguage of PLTL, the logical semantics of TeDiLog is supported by PLTL logical consequence. The operational semantics of TeDiLog is based on TRS-resolution. TeDiLog allows both eventualities and always-formulas to occur in clause heads and also in clause bodies. To the best of our knowledge, TeDiLog is the first declarative temporal logic programming language that achieves this high degree of expressiveness. Since the tableau method presented in this thesis is able to detect that the fulfillment of an eventuality is prevented by a hidden invariant without checking for it by means of an extra process, since our finitary sequent calculi do not include invariant-based rules and since our resolution method dispenses with invariant generation, we say that our deduction methods are invariant-free.

Uptake and intracytoplasmic storage of pigmented particles by human CD34+stromal cells/telocytes: endocytic property of telocytes

We studied the phagocytic-like capacity of human CD34+ stromal cells/telocytes (TCs). For this, we examined segments of the colon after injection of India ink to help surgeons localize lesions identified at endoscopy. Our results demonstrate that CD34+ TCs have endocytic properties (phagocytic-like TCs: phTCs), with the capacity to uptake and store India ink particles. phTCs conserve the characteristics of TCs (long, thin, bipolar or multipolar, moniliform cytoplasmic processes/telopodes, with linear distribution of the pigment) and maintain their typical distribution. Likewise, they are easily distinguished from pigment-loaded macrophages (CD68+ macrophages, with oval morphology and coarse granules of pigment clustered in their cytoplasm). A few c-kit/CD117+ interstitial cells of Cajal also incorporate pigment and may conserve the phagocytic-like property of their probable TC precursors. CD34+ stromal cells in other locations (skin and periodontal tissues) also have the phagocytic-like capacity to uptake and store pigments (hemosiderin, some components of dental amalgam and melanin). This suggests a function of TCs in general, which may be related to the transfer of macromolecules in these cells. Our ultrastructural observation of melanin-storing stromal cells with characteristics of TCs (telopodes with dichotomous branching pattern) favours this possibility. In conclusion, intestinal TCs have a phagocytic-like property, a function that may be generalized to TCs in other locations. This function (the ability to internalize small particles), together with the capacity of these cells to release extracellular vesicles with macromolecules, could close the cellular bidirectional cooperative circle of informative exchange and intercellular interactions.

Coincidence point theorems in quasi-metric spaces without assuming the mixed monotone property and consequences in G-metric spaces

In this paper, we present some coincidence point theorems in the setting of quasi-metric spaces that can be applied to operators which not necessarily have the mixed monotone property. As a consequence, we particularize our results to the field of metric spaces, partially ordered metric spaces and G-metric spaces, obtaining some very recent results. Finally, we show how to use our main theorems to obtain coupled, tripled, quadrupled and multidimensional coincidence point results.

Leukemia-Associated Mutations in Nucleophosmin Alter Recognition by CRM1: Molecular Basis of Aberrant Transport

Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein, normally enriched in nucleoli, that performs several activities related to cell growth. NPM mutations are characteristic of a subtype of acute myeloid leukemia (AML), where mutant NPM seems to play an oncogenic role. AML-associated NPM mutants exhibit altered subcellular traffic, being aberrantly located in the cytoplasm of leukoblasts. Exacerbated export of AML variants of NPM is mediated by the nuclear export receptor CRM1, and due, in part, to a mutationally acquired novel nuclear export signal (NES). To gain insight on the molecular basis of NPM transport in physiological and pathological conditions, we have evaluated the export efficiency of NPM in cells, and present new data indicating that, in normal conditions, wild type NPM is weakly exported by CRM1. On the other hand, we have found that AML-associated NPM mutants efficiently form complexes with CRM1HA (a mutant CRM1 with higher affinity for NESs), and we have quantitatively analyzed CRM1HA interaction with the NES motifs of these mutants, using fluorescence anisotropy and isothermal titration calorimetry. We have observed that the affinity of CRM1HA for these NESs is similar, which may help to explain the transport properties of the mutants. We also describe NPM recognition by the import machinery. Our combined cellular and biophysical studies shed further light on the determinants of NPM traffic, and how it is dramatically altered by AML-related mutations.

Approximate Solutions by Truncated Taylor Series Expansions of Nonlinear Differential Equations and Related Shadowing Property with Applications

This paper investigates the errors of the solutions as well as the shadowing property of a class of nonlinear differential equations which possess unique solutions on a certain interval for any admissible initial condition. The class of differential equations is assumed to be approximated by well-posed truncated Taylor series expansions up to a certain order obtained about certain, in general nonperiodic, sampling points t(i) is an element of [t(0), t(J)] for i = 0, 1, . . . , J of the solution. Two examples are provided.