A Semantic Approach to Decidability in Epistemic Planning

The use of Dynamic Epistemic Logic (DEL) in multi-agent planning has led to a widely adopted action formalism that can handle nondeterminism, partial observability and arbitrary knowledge nesting. As such expressive power comes at the cost of undecidability, several decidable fragments have been isolated, mainly based on syntactic restrictions of the action formalism. In this paper, we pursue a novel semantic approach to achieve decidability. Namely, rather than imposing syntactical constraints, the semantic approach focuses on the axioms of the logic for epistemic planning. Specifically, we augment the logic of knowledge S5n and with an interaction axiom called (knowledge) commutativity, which controls the ability of agents to unboundedly reason on the knowledge of other agents. We then provide a threefold contribution. First, we show that the resulting epistemic planning problem is decidable. In doing so, we prove that our framework admits a finitary non-fixpoint characterization of common knowledge, which is of independent interest. Second, we study different generalizations of the commutativity axiom, with the goal of obtaining decidability for more expressive fragments of DEL. Finally, we show that two well-known epistemic planning systems based on action templates, when interpreted under the setting of knowledge, conform to the commutativity axiom, hence proving their decidability

Data-aware conformance checking with SMT

Conformance checking is a key process mining task to confront the normative behavior imposed by a process model with the actual behavior recorded in a log. While this problem has been extensively studied for pure control-flow processes, data-aware conformance checking has received comparatively little attention. In this paper, we tackle the conformance checking problem for the challenging scenario of processes that combine data and control-flow dimensions. Concretely, we adopt the formalism of data Petri nets (DPNs) and show how solid, well-established automated reasoning techniques from the area of Satisfiability Modulo Theories (SMT) can be effectively harnessed to compute conformance metrics and optimal data-aware alignments. To this end, we introduce the CoCoMoT (Computing Conformance Modulo Theories) framework, with a fourfold contribution. First, we show how SMT allows to leverage SAT-based encodings for the pure control-flow setting to the data-aware case. Second, we introduce a novel preprocessing technique based on a notion of property-preserving clustering, to speed up the computation of conformance checking outputs. Third, we show how our approach extends seamlessly to the more comprehensive conformance checking artifacts of multi- and anti-alignments. Fourth, we describe a proof-of-concept implementation based on state-of-the-art SMT solvers, and report on experiments. Finally, we discuss how CoCoMoT directly lends itself to further process mining tasks like log analysis by clustering and model repair, and the use of SMT facilitates the support of even richer multi-perspective models, where, for example, more expressive DPN guards languages are considered or generic datatypes (other than integers or reals) are employed

FluoroSpot assay to analyze SARS-CoV-2-specific T cell responses

Monitoring antigen-specific T cell frequency and function is essential to assess the host immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we present a FluoroSpot assay for concurrently detecting ex vivo antiviral cytokine production by SARS-CoV-2-specific T cells following peptide stimulation. We then detail intracellular cytokine staining by flow cytometry to further validate the FluoroSpot assay results and define the specific T cell subpopulations. For complete details on the use and execution of this protocol, please refer to Tiezzi et al. (2023).

Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy

NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network)

Insights Into the Immune Response of the Black Soldier Fly Larvae to Bacteria

In insects, a complex and effective immune system that can be rapidly activated by a plethora of stimuli has evolved. Although the main cellular and humoral mechanisms and their activation pathways are highly conserved across insects, the timing and the ef\ufb01cacy of triggered immune responses can differ among different species. In this scenario, an insect deserving particular attention is the black soldier \ufb02 y (BSF), Hermetia illucens (Diptera: Stratiomyidae). Indeed, BSF larvae can be reared on a wide range of decaying organic substrates and, thanks to their high protein and lipid content, they represent a valuable source of macromolecules useful for different applications (e.g., production of feedstuff, bioplastics, and biodiesel), thus contributing to the development of circular economy supply chains for waste valorization. However, decaying substrates bring the larvae into contact with different potential pathogens that can challenge their health status and growth. Although these life strategies have presumably contributed to shape the evolution of a sophisticated and ef \ufb01 cient immune system in this dipteran, knowledge about its functional features is still fragmentary. In the present study, we investigated the processes underpinning the immune response to bacteria in H. illucens larvae and characterized their reaction times. Our data demonstrate that the cellular and humoral responses in this insect show different kinetics: phagocytosis and encapsulation are rapidly triggered after the immune challenge, while the humoral components intervene later. Moreover, although both Gram-positive and Gram-negative bacteria are completely removed from the insect body within a few hours after injection, Gram-positive bacteria persist in the hemolymph longer than do Gram-negative bacteria. Finally, the activity of two key actors of the humoral response, i.e., lysozyme and phenoloxidase, show unusual dynamics as compared to other insects. This study represents the \ufb01 rst detailed characterization of the immune response to bacteria of H. illucens larvae, expanding knowledge on the defense mechanisms of this insect among Diptera. This information is a prerequisite to manipulating the larval immune response by nutritional and environmental factors to increase resistance to pathogens and optimize health status during mass rearing

Clinical Processes - The Killer Application for Constraint-Based Process Interactions?

For more than a decade, the interest in aligning information systems in a process-oriented way has been increasing. To enable operational support for business processes, the latter are usually specified in an imperative way. The resulting process models, however, tend to be too rigid to meet the flexibility demands of the actors involved. Declarative process modeling languages, in turn, provide a promising alternative in scenarios in which a high level of flexibility is demanded. In the scientific literature, declarative languages have been used for modeling rather simple processes or synthetic examples. However, to the best of our knowledge, they have not been used to model complex, real-world scenarios that comprise constraints going beyond control-flow. In this paper, we propose the use of a declarative language for modeling a sophisticated healthcare process scenario from the real world. The scenario is subject to complex temporal constraints and entails the need for coordinating the constraint-based interactions among the processes related to a patient treatment process. As demonstrated in this work, the selected real process scenario can be suitably modeled through a declarative approach.Ministerio de Economía y Competitividad TIN2016-76956-C3-2-RMinisterio de Economía y Competitividad TIN2015-71938-RED

Electrostatic Tuning of the Ligand Binding Mechanism by Glu27 in Nitrophorin 7.

Nitrophorins (NP) 1-7 are NO-carrying heme proteins found in the saliva of the blood-sucking insect Rhodnius prolixus. The isoform NP7 displays peculiar properties, such as an abnormally high isoelectric point, the ability to bind negatively charged membranes, and a strong pH sensitivity of NO affinity. A unique trait of NP7 is the presence of Glu in position 27, which is occupied by Val in other NPs. Glu27 appears to be important for tuning the heme properties, but its influence on the pH-dependent NO release mechanism, which is assisted by a conformational change in the AB loop, remains unexplored. Here, in order to gain insight into the functional role of Glu27, we examine the effect of Glu27 → Val and Glu27 → Gln mutations on the ligand binding kinetics using CO as a model. The results reveal that annihilation of the negative charge of Glu27 upon mutation reduces the pH sensitivity of the ligand binding rate, a process that in turn depends on the ionization of Asp32. We propose that Glu27 exerts a through-space electrostatic action on Asp32, which shifts the pKa of the latter amino acid towards more acidic values thus reducing the pH sensitivity of the transition between open and closed states

Metagenome-sourced microbial chitinases as potential insecticide proteins

Microbial chitinases are gaining interest as promising candidates for controlling plant pests. These enzymes can be used directly as biocontrol agents as well as in combination with chemical pesticides or other biopesticides, reducing their environmental impact and/or enhancing their efficacy. Chitinolytic enzymes can target two different structures in insects: the cuticle and the peritrophic matrix (PM). PM, formed by chitin fibrils connected to glycoproteins and proteoglycans, represents a physical barrier that plays an essential role in midgut physiology and insect digestion, and protects the absorptive midgut epithelium from food abrasion or pathogen infections. In this paper, we investigate how two recently discovered metagenomesourced chitinases (Chi18H8 and 53D1) affect, in vitro and in vivo, the PM integrity of Bombyx mori, a model system among Lepidoptera. The two chitinases were produced in Escherichia coli or, alternatively, in the unconventional \u2013 but more environmentally acceptable \u2013 Streptomyces coelicolor. Although both the proteins dramatically altered the structure of B. mori PM in vitro, when administered orally only 53D1 caused adverse and marked effects on larval growth and development, inducing mortality and reducing pupal weight. These in vivo results demonstrate that 53D1 is a promising candidate as insecticide protein