Dynamic of lipid droplets and gene expression in response to beta-aminoisobutyric acid treatment on 3T3-L1 cells

Research on adipobiology has recognized the browning process of white adipocytes as a potential therapeutic strategy for the treatment of obesity and related morbidities. Physical exercise stimulates the secretion of myokines, such as \uf062-aminoisobutyric acid (BAIBA), which in turn promotes adaptive thermogenesis. White adipocyte conversion to brown cells involves dynamic changes in lipid droplet (LD) dimension and in the transcription of brown-specific marker genes. This study analyzes the effect of different doses of BAIBA and at different days of development on 3T3-L1 cells by evaluating morphological changes in LDs and the expression of browning gene markers. Results suggested that the highest concentration of BAIBA after 4 days of differentiation produced the most significant effects. The number of LDs per cell increased in comparison to control cells, whereas the surface area significantly decreased. Brown adipocyte markers were up-regulated, but the effect of treatment was lost at 10 days of differentiation. The thermogenic program induced by BAIBA may reflect a rapid adaptation of adipose tissue to physical exercise. This connection stresses the beneficial impact of physical exercise on metabolic health

Crossing the Undecidability Border with Extensions of Propositional Neighborhood Logic over Natural Numbers

Propositional Neighborhood Logic (PNL) is an interval temporal logic featuring two modalities corresponding to the relations of right and left neighborhood between two intervals on a linear order (in terms of Allen's relations, meets and met by). Recently, it has been shown that PNL interpreted over several classes of linear orders, including natural numbers, is decidable (NEXPTIME-complete) and that some of its natural extensions preserve decidability. Most notably, this is the case with PNL over natural numbers extended with a limited form of metric constraints and with the future fragment of PNL extended with modal operators corresponding to Allen's relations begins, begun by, and before. This paper aims at demonstrating that PNL and its metric version MPNL, interpreted over natural numbers, are indeed very close to the border with undecidability, and even relatively weak extensions of them become undecidable. In particular, we show that (i) the addition of binders on integer variables ranging over interval lengths makes the resulting hybrid extension of MPNL undecidable, and (ii) a very weak first-order extension of the future fragment of PNL, obtained by replacing proposition letters by a restricted subclass of first-order formulae where only one variable is allowed, is undecidable (in contrast with the decidability of similar first-order extensions of point-based temporal logics)

A novel automata-theoretic approach to timeline-based planning

Timeline-based planning is a well-established approach successfully employed in a number of application domains. A very restricted fragment, featuring only bounded temporal relations and token durations, is expressive enough to capture action-based temporal planning. As for computational complexity, it has been shown to be EXPSPACE-complete when unbounded temporal relations, but only bounded token durations, are allowed. In this paper, we present a novel automata-theoretic characterisation of timeline-based planning where the existence of a plan is shown to be equivalent to the nonemptiness of the language recognised by a nondeterministic finite-state automaton that suitably encodes all the problem constraints (timelines and synchronisation rules). Besides allowing us to restate known complexity results in a fairly natural and compact way, such an alternative characterisation makes it possible to finally establish the exact complexity of the full version of the problem with unbounded temporal relations and token durations, which was still open and turns out to be EXPSPACE-complete. Moreover, the proposed technique is general enough to cope with (infinite) recurrent goals, which received little attention so far, despite being quite common in real-word application scenarios

Microparticulate polyelectrolyte complexes for gentamicin transport across intestinal epithelial

Polysaccharide microparticles for the oral administration of gentamicin were designed in order to obtainan increased drug absorption by means of microparticle transport across the intestinal epithelia. Alginate/chitosan microparticles with a size of ∼ 2 μm were developed by spray-drying a water solution containingthe drug complexed with the polyanionic alginate and subsequent alginate cross-linking process bycalcium ions and chitosan. The pre-formulation study, performed by changing the concentration of bothcross-linkers, led to the selection of the most suitable formulation which was assayed for its capacity to be translocated across intestinal epithelia, via both M cells contained in Follicle Associated Epithelium (FAE) ofPeyer’s patches and enterocytes of the mucosal epithelium. An ex vivo perfusion technique of rabbit andrat intestinal tissues containing Peyer’s patches combined with an in vitro method by using Caco-2 cellmonolayers demonstrated the microparticulate carrier ability to be taken up by both M cells and enterocytes.However, only the endocytosis by M cells appeared to provide the microparticle transport from theepithelium toward deeper sub-epithelial regions

Complexity of qualitative timeline-based planning

The timeline-based approach to automated planning was originally developed in the context of space missions. In this approach, problem domains are expressed as systems consisting of independent but interacting components whose behaviors over time, the timelines, are governed by a set of temporal constraints, called synchronization rules. Although timeline-based system descriptions have been successfully used in practice for decades, the research on the theoretical aspects only started recently. In the last few years, some interesting results have been shown concerning both its expressive power and the computational complexity of the related planning problem. In particular, the general problem has been proved to be EXPSPACE-complete. Given the applicability of the approach in many practical scenarios, it is thus natural to ask whether computationally simpler but still expressive fragments can be identified. In this paper, we study the timeline-based planning problem with the restriction that only qualitative synchronization rules, i.e., rules without explicit time bounds in the constraints, are allowed. We show that the problem becomes PSPACE-complete

Decidability and complexity of the fragments of the modal logic of Allen's relations over the rationals

Interval temporal logics provide a natural framework for temporal reasoning about interval structures over linearly ordered domains, where intervals are taken as first-class citizens. Their expressive power and computational behaviour mainly depend on two parameters: the set of modalities they feature and the linear orders over which they are interpreted. In this paper, we consider all fragments of Halpern and Shoham's interval temporal logic hs with a decidable satisfiability problem over the rationals, and we provide a complete classification of them in terms of their expressiveness and computational complexity by solving the last few open problems

Monitors that Learn from Failures: Pairing STL and Genetic Programming

In several domains, systems generate continuous streams of data during their execution, including meaningful telemetry information, that can be used to perform tasks like preemptive failure detection. Deep learning models have been exploited for these tasks with increasing success, but they hardly provide guarantees over their execution, a problem which is exacerbated by their lack of interpretability. In many critical contexts, formal methods, which ensure the correct behaviour of a system, are thus necessary. However, specifying in advance all the relevant properties and building a complete model of the system against which to check them is often out of reach in real-world scenarios. To overcome these limitations, we design a framework that resorts to monitoring, a lightweight runtime verification technique that does not require an explicit model specification, and pairs it with machine learning. Its goal is to automatically derive relevant properties, related to a bad behaviour of the considered system, encoded by means of formulas of Signal Temporal Logic (STL). Results based on experiments performed on well-known benchmark datasets show that the proposed framework is able to effectively anticipate critical system behaviours in an online setting, providing human-interpretable results

The role of protamine amount in the transfection performance of cationic SLN designed as a gene nanocarrier

Cationic solid lipid nanoparticles (SLN) have been recently proposed as non-viral vectors in systemic gene therapy. The aim of this study was to evaluate the effect of the protamine amount used as the transfection promoter in SLN-mediated gene delivery. Three protamine-SLN samples (Pro25, Pro100, and Pro200) prepared by adding increasing amounts of protamine were characterized for their size, zeta potential, and protamine loading level. The samples were evaluated for pDNA complexation ability by gel-electrophoresis analysis and for cytotoxicity and transfection efficiency by using different cell lines (COS-I, HepG2, and Na1300). The size of SLN was ~230 nm and only Pro200 showed few particle aggregates. Unlike the Pro25 sample with the lowest protamine loading level, the others SLN samples (Pro100 and Pro200) exhibited a good ability in complexing pDNA. A cell-line dependent cytotoxicity lower than that of the positive control PEI (polyethilenimmine) was observed for all the SLN. Among these, only Pro100, having an intermediate amount of protamine, appeared able to promote pDNA cell transfer, especially in a neuronal cell line (Na1300). In conclusion, the amount of protamine as the transfection promoter in SLN affects not only the gene delivery ability of SLN but also their capacity to transfer genes efficiently to specific cell types