Cooperation and Competition in ALIAS: A Logic Framework for Agents that Negotiate

This paper presents ALIAS, an agent architecture based on intelligent logic agents, where the main form of agent reasoning is abduction. The system is particularly suited for solving problems where knowledge is incomplete, where agents may need to make reasonable hypotheses about the problem domain and other agents, and where the raised hypotheses have to be consistent for the overall set of agents. ALIAS agents are pro-active, exhibiting a goal-directed behavior, and autonomous, since each one can solve problems using its own private knowledge base. ALIAS agents are also social, because they are able to interact with other agents, in order to cooperatively solve problems. The coordination mechanisms are modeled by means of LAILA, a logic-based language which allows to express intra-agent reasoning and inter-agent coordination. As an application, we show how LAILA can be used to implement inter-agent dialogues, e.g., for negotiation. In particular, LAILA is well-suited to coordinate the process of negotiation aimed at exchanging resources between agents, thus allowing them to execute the plans to achieve their goals.     

Specification and Verification of Agent Interaction using Social Integrity Constraints

In this paper we propose a logic-based social approach to the specification and verification of agent interaction. We firstly introduce integrity constraints about social acts (called Social Integrity Constraints) as a formalism to express interaction protocols and to give a social semantics to the behavior of agents, focusing on communicative acts. Then, we discuss several possible kinds of verification of agent interaction, and we show how social integrity constraints can be used to verify some properties in this respect. We focus our attention on static verification of compliance of agent specifications to interaction protocols, and on run-time verification, based on agents' observable behavior. We adopt as a running example the NetBill security transaction protocol for the selling and delivery of information goods.     

Effect of geometry and green density on the anisotropic sintering shrinkage of axisymmetric iron parts

Sintering shrinkage of prior cold compacted iron rings with different geometry (height to wall thickness ratio) and green density in the 6.5–7.3?g/cm³ range was investigated. It displays a minimum at an intermediate green density. Axial, tangential and radial shrinkages are different, due to the gradients of green density along the axial and the radial directions. Therefore, the effect of height on shrinkage and its anisotropy is the result of their effect on the stress distribution in the green parts during cold compaction, and the resulting green density and deformation experienced by the powder. Anisotropy decreases on increasing shrinkage.     

Integrated membrane operations in the ethylene oxide production

Petrochemical industry, highly energy and capital intensive, might significantly benefit from the implementation of membrane operations for meeting stringent environmental standards, controlling production cost and final product's quality. Membrane units have been proved effective for improving the efficiency of different industrial productions. Ethylene oxide (EO), an important petrochemical intermediate, is produced by selective catalytic oxidation of ethylene, a valuable hydrocarbon feedstock. In this study, the EO manufacturing cycle is redesigned by integrating different membrane operations. Both the conversion and separation sections of the plant are investigated, considering the use of membrane reactors (MRs) for the separate feeding of the oxidant, membrane contactors (MCs) for the absorption of EO and carbon dioxide, and gas separation (GS) membrane units for the hydrocarbon recovery before their being recycled to the reactor. Design considerations are provided, and the benefits coming from each membrane operation, as well as from their synergic integration, are outlined with particular attention to environmental impact, raw materials and energy consumption.     

Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.     

Hereditary Prostate Cancer: Genes Related,Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.     

Putative Circulating MicroRNAs Are Able to Identify Patients with Mitral Valve Prolapse and Severe Regurgitation

Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.     

Direct Application of Rep‐PCR on Type I Sourdough Matrix to Monitor the Dominance and Persistence of a Lactobacillus plantarum Starter Throughout Back‐Slopping

This study describes the optimization and application of repetitive element‐PCR (rep‐PCR) technique directly on microbial DNA extracted from type I sourdoughs for fast monitoring of a Lb. plantarum starter strain (P1FMC) throughout daily back‐slopping. The challenge was to follow and study the performance of a starter culture directly in sourdoughs without cultivation on selective media. The extraction of good quality microbial DNA suitable for amplification from a complex matrix such as dough was the first target. In addition, the objective to obtain a clear rep‐PCR profile referable to a specific starter strain among a microbial community was pursued. Co‐inoculum trials, in flour matrix, with Lb. plantarum P1FMC and L. lactis LC71 strains and, subsequently, type I sourdough back‐slopping trials were performed. The rep‐PCR amplification profiles obtained were clearly referable to that of Lb. plantarum P1FMC starter in both co‐inoculum trials (also when it was present with one order of magnitude less with respect to L. lactis LC71) and back‐slopping trials where it dominated the fermentation process with loads of 10⁸ cfu g^?1 and prevailed on the autochthonous microbiota. Thus, the approach proposed in this paper could be considered a methodological advancement, based on a culture‐independent one‐step rep‐PCR, suitable for fast monitoring of starter performance.