Timed tree automata with an application to temporal logic

Finite automata on -sequences and -trees were introduced in the sixties by Büchi, McNaughton and Rabin. Finite automata on timed -sequences were introduced by Alur and Dill. In this paper we extend the theory of timed -sequences to -trees. The main motivation is the introduction of a new way to specify real-time systems and to study, using automata-theoretic techniques, branching-time temporal logics with timing constraints. We study closure properties and decision problems for the obtained classes of timed -tree languages. In particular, we show the decidability of the emptiness problem. As an application of the introduced theory, we give a new decidable branching time temporal logic (STCTL) whose semantics is based upon timed -trees. Received: 8 September 1997 / 27 June 2001     

Aberrant Expression of Long Non Coding RNA HOTAIR and De-Regulation of the Paralogous 13 HOX Genes Are Strongly Associated with Aggressive Behavior of Gastro-Entero-Pancreatic Neuroendocrine Tumors

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA HOTAIR in GEP-NENs. The expression of HOX genes is gradually lost in the transition from GEP NET G1 to NET/NEC G3 tumors, while HOTAIR expression, inversely correlated with HOX genes expression and weakly expressed in low-grade GEP NENs, becomes aberrant in NET G3 and NEC G3 categories. Our data highlights their potential role in the molecular stratification of GEP-NENs by suggesting new prognostic markers and potential therapeutic targets.     

Combinations of Histone Deacetylase Inhibitors with Distinct Latency Reversing Agents Variably Affect HIV Reactivation and Susceptibility to NK Cell-Mediated Killing of T Cells That Exit Viral Latency

The ‘shock-and-kill’ strategy to purge the latent HIV reservoir relies on latency-reversing agents (LRAs) to reactivate the provirus and subsequent immune-mediated killing of HIV-expressing cells. Yet, clinical trials employing histone deacetylase inhibitors (HDACis; Vorinostat, Romidepsin, Panobinostat) as LRAs failed to reduce the HIV reservoir size, stressing the need for more effective latency reversal strategies, such as 2-LRA combinations, and enhancement of the immune responses. Interestingly, several LRAs are employed to treat cancer because they up-modulate ligands for the NKG2D NK-cell activating receptor on tumor cells. Therefore, using in vitro T cell models of HIV latency and NK cells, we investigated the capacity of HDACis, either alone or combined with a distinct LRA, to potentiate the NKG2D/NKG2D ligands axis. While Bortezomib proteasome inhibitor was toxic for both T and NK cells, the GS-9620 TLR-7 agonist antagonized HIV reactivation and NKG2D ligand expression by HDACis. Conversely, co-administration of the Prostratin PKC agonist attenuated HDACi toxicity and, when combined with Romidepsin, stimulated HIV reactivation and further up-modulated NKG2D ligands on HIV⁺ T cells and NKG2D on NK cells, ultimately boosting NKG2D-mediated viral suppression by NK cells. These findings disclose limitations of LRA candidates and provide evidence that NK cell suppression of reactivated HIV may be modulated by specific 2-LRA combinations.     

Complexity reduction and kaizen events to balance manual assembly lines: an application in the field

Notwithstanding the existence of a broad research base on assembly line balancing (ALB), companies do not use the mathematical approaches developed in the literature to configure assembly lines. This article aims to fill the gap between research and application by presenting and testing in a real industrial context a methodology based on complexity reduction and kaizen events. First, the methodology supports reducing the complexity that affects real-life assembly systems in terms of the variety of, e.g. finished products, materials and parts. Next, the methodology proposes the conduction of kaizen events by using lean manufacturing tools, such as process analysis, time observation, waste identification, workstation standard documents and yamazumi charts. The methodology is successfully applied to a case study that describes its use in the confectionery process for a major chocolatier company along with the results of the application. The main contribution of this paper consists in presenting a method to manage the line balancing activity within everyday industrial realities, helping practitioners to improve and maintain the performance over time.     

Antioxidant properties of different milk fermented with lactic acid bacteria and yeast

The antioxidant properties of nine different samples of freshly drawn, pasteurised and UHT milk were examined before and after fermentation with several lactobacilli, individually and in combination with the yeast Saccharomyces boulardii. The results showed no statistical differences for the content in proteins, fats and carbohydrates of the different milk. The antioxidant properties of the unfermented milk were positively affected by the thermal treatment. All samples of fermented milk had a greater antioxidant activity than unfermented but only for the freshly drawn milk that increase was significantly different. The co‐incubation of lactobacilli with the yeast determined a stronger antioxidant activity especially for the freshly drawn milk. The stability of the tested strains during storage in standard conditions was determined in UHT fermented milk to enable a possible use in probiotic food production. The results showed that the yeast incubated with lactobacilli determined an improvement of the viability of bacteria.     

Mechanical and rheological properties of fresh egg pasta as affected by shell egg production factors

The aim of this work was to study the influence of hen age and housing system on egg performances in fresh pasta production, focusing on mechanical and rheological properties of pasta. Samples of pasta were prepared with eggs laid by Hy‐Line Brown hens (from 27 to 68 weeks old) housed in conventional cage, barn and organic systems. Only hen age significantly affected pasta properties. In particular, as regards raw pasta, the loosest structure was obtained using eggs laid by the youngest hens (27–30 weeks old). On the contrary, in cooked pasta, the weakest structure was observed when eggs were laid by hens aged 53–68 weeks. However, differences, although significant, were small and thus most likely not sensorially perceivable. Significant correlations were found between mechanical and rheological properties of raw fresh egg pasta, meaning that small deformation measurements are as valuable as large deformation tests for the characterisation of this product.     

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.