Prader Willi locus Snord116 RNA regulates hypothalamic functions: sleep and temperature

Sleep is a complex behavior and it is hierarchically regulated involving several brain regions, neurotransmitters, and genes that co-operate in building modulatory mechanisms aimed at controlling and maintaining sleep. Specifically, this thesis attempts to address/understand how genomic imprinting, which affect a subset of genes in mammals resulting in a monoallelic expression, may regulate sleep. One of the main brain regions involved in sleep regulation is the hypothalamus. Within the hypothalamic region imprinted genes are highly expressed. Interestingly, it has been described that hypothalamic insufficiency caused by lack of paternal expression of chromosome 15q11- q13, leads to Prader-Willi syndrome (PWS). Specifically, the microdeletion of the small nuclear ribonucleic acid (RNA)-116 (SNORD116) cluster within the PWS locus plays a major role in developing the main endophenotypes that characterize this syndrome (i.e. REM sleep dysfunction, hyperphagia and temperature instability). However, what could be the role of the paternally imprinted gene Snord116 in the hypothalamic function is unknown. Additionally, is still unclear the specific contribution of the Snord116 gene in developing the PWS symptoms. Since these unresolved points my research has been split into three parts: In the first part of this research, it has been shown that the paternally imprinted gene Snord116 plays a crucial role in the formation and organization of the orexin (OX) and melanin concentrating hormone (MCH) systems, the two main neuro-modulatory systems within the lateral hypothalamus (LH). Moreover, a compromised neuronal dynamic in the LH and a sleep- wake regulation of mice with paternal deletion of Snord116 (PWScrm+/p-) is observed. This abnormal neuronal dynamic is accompanied by a significant reduction in OX neurons in the LH of mutant mice. For this reason, it is proposed that the dysregulation of rapid eye movement (REM) sleep, food intake and temperature control observed in PWS mice are potentially due to this imbalance between OX- and MCH-expressing neurons in the LH as observed in mutant mice. In the second part of this research, it has been investigated the microstructural electrophysiological components of sleep, such as REM sleep features and sleep spindles during non-REM sleep. Indeed, REM sleep is thought to contribute to neuronal network formation early in brain development, while spindles are markers of thalamocortical processes. In neurodevelopmental disorders both sleep structures (REM and sleep spindles) are often compromised and this influence functional properties of cortical neurons. These results indicate 1 that REM sleep properties and its occurrence (REM sleep episodes classified as short-and long REM sleep episode) throughout the sleep-wake cycles are selectively influenced by the Snord116 gene in mice. Moreover, the specific abnormalities in sleep spindles in PWS model systems, indicate that these sleep features may be translated as potential biomarkers in human PWS sufferers. In the third part of this research, it has been proposed a new therapeutic approach for PWS patients aiming to ameliorate the sleep phenotypes that significantly compromise the quality of life of these patients. Pitolisant (a wake-promoting drug) was orally administrated in mice carrying the paternal deletion of the Snord116 gene that are affected by REM sleep alteration coupled with a reduction of the OX neurons. Overall the results of this research show that Pitolisant ameliorates the REM sleep alteration in these mice, although other studies are needed to clarify whether this drug may be easily translated/used in clinics. In conclusion, this thesis provides support for the important role of Snord116 in the regulation of REM sleep and its propensity and its regulatory mechanisms in the hypothalamus. Finally, a new pharmacological approach for PWS by using Pitolisant has been proposed to ameliorate the sleep alteration that significantly affects the PWS patients

Belief Revision in Structured Probabilistic Argumentation

In real-world applications, knowledge bases consisting of all the information at hand for a specific domain, along with the current state of affairs, are bound to contain contradictory data coming from different sources, as well as data with varying degrees of uncertainty attached. Likewise, an important aspect of the effort associated with maintaining knowledge bases is deciding what information is no longer useful; pieces of information (such as intelligence reports) may be outdated, may come from sources that have recently been discovered to be of low quality, or abundant evidence may be available that contradicts them. In this paper, we propose a probabilistic structured argumentation framework that arises from the extension of Presumptive Defeasible Logic Programming (PreDeLP) with probabilistic models, and argue that this formalism is capable of addressing the basic issues of handling contradictory and uncertain data. Then, to address the last issue, we focus on the study of non-prioritized belief revision operations over probabilistic PreDeLP programs. We propose a set of rationality postulates -- based on well-known ones developed for classical knowledge bases -- that characterize how such operations should behave, and study a class of operators along with theoretical relationships with the proposed postulates, including a representation theorem stating the equivalence between this class and the class of operators characterized by the postulates

Model contractions on description logics

When using tableaux algorithms to reason about Description Logics (DLs), new information is inferred from the models considered while trying to achieve knowledge satisfiability. By focusing the ontology change problem, we consider an environment where DLs are the logical formalization to express knowledge bases in the web, and the integration of distributed ontologies is developed under new extensions of the belief revision theories originally exposed in [1]. Hence, a reinforced theory arises in order to properly apply change operations over models, considering new inferred information and assumed beliefs in each possible world. As a result, a new type of contraction operator is proposed and its success postulate analyzed.Red de Universidades con Carreras en Informática (RedUNCI

Datalog± Ontology Consolidation

Knowledge bases in the form of ontologies are receiving increasing attention as they allow to clearly represent both the available knowledge, which includes the knowledge in itself and the constraints imposed to it by the domain or the users. In particular, Datalog ± ontologies are attractive because of their property of decidability and the possibility of dealing with the massive amounts of data in real world environments; however, as it is the case with many other ontological languages, their application in collaborative environments often lead to inconsistency related issues. In this paper we introduce the notion of incoherence regarding Datalog± ontologies, in terms of satisfiability of sets of constraints, and show how under specific conditions incoherence leads to inconsistent Datalog ± ontologies. The main contribution of this work is a novel approach to restore both consistency and coherence in Datalog± ontologies. The proposed approach is based on kernel contraction and restoration is performed by the application of incision functions that select formulas to delete. Nevertheless, instead of working over minimal incoherent/inconsistent sets encountered in the ontologies, our operators produce incisions over non-minimal structures called clusters. We present a construction for consolidation operators, along with the properties expected to be satisfied by them. Finally, we establish the relation between the construction and the properties by means of a representation theorem. Although this proposal is presented for Datalog± ontologies consolidation, these operators can be applied to other types of ontological languages, such as Description Logics, making them apt to be used in collaborative environments like the Semantic Web.Fil: Deagustini, Cristhian Ariel David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias e Ingeniería de la Computación. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Instituto de Ciencias e Ingeniería de la Computación; ArgentinaFil: Martinez, Maria Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias e Ingeniería de la Computación. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Instituto de Ciencias e Ingeniería de la Computación; ArgentinaFil: Falappa, Marcelo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias e Ingeniería de la Computación. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Instituto de Ciencias e Ingeniería de la Computación; ArgentinaFil: Simari, Guillermo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias e Ingeniería de la Computación. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Instituto de Ciencias e Ingeniería de la Computación; Argentin

Consolidation of plausiblity relations in multi-agent systems

Within the context of multi-agent systems, an agent may often ¯nd itself in a position where it receives information through informants. These informants are independent agents who have their own interests and, therefore, are not necessarily completely reliable. It is natural for an agent to be more inclined to believe one informant over another, especially if the informant has proven itself reliable over a period of time. This preference is stored in a plausibility relation, a partial order indicating the relative credibility of the agent's informants. Through careless expansion or other means, inconsistencies may be introduced into the plausibility relation. A consolidation operator is proposed and characterized through a set of postulates. Alternative constructions are discussed. A non-prioritized revision operator for plausibility relations, based on consolidation, is also presented.Eje: Sistemas inteligentesRed de Universidades con Carreras en Informática (RedUNCI

Some approaches to Belief Bases Merge

In this work, we de fine some non-prioritized merge operators, that is, operators for the consistent union of belief bases. We de ne some postulates for several kinds of merge operator and we give different constructions: trivial merge, partial meet merge and kernel merge. For some constructions we provide representation theorems linking construction with a set of postulates. Finally, we propose that the formulated operators can be used in some multi-agent systemsVII Workshop de Agentes y Sistemas Inteligentes (WASI)Red de Universidades con Carreras en Informática (RedUNCI

Notions of relevance for modeling the dynamics of belief

We identify different kinds of relevance relations between formulas that emerge in the process of belief revision. Informal definitions for alternative notions of relevance are suggested and a set of schemas and intuitive postulates for formalizing these notions are proposed. The notions of relevance proposed here are shown to be good candidates for modeling the process of belief revision.Eje: Programación lógicaRed de Universidades con Carreras en Informática (RedUNCI

Tableau calculi for description logics revision

Focusing on the Ontology Change problem, we consider an environment where Description Logics (DLs) are the logical formalization to express knowledge bases, and the integration of distributed ontologies is developed under new extensions and modifications of the Belief Revision theories yielded originally in [2]. When using tableaux algorithms to reason about DLs, new information is yielded from the models considered in order to achieve knowledge satisfiability. Here a whole new theory have to be reinforced in order to adapt belief revision definitions and postulates to properly react over beliefs on extensions generated from these DL’s reasoning services. In this text we give a brief background of these formalisms and comment the research lines to be taken in our way to this goal.Eje: Agentes y Sistemas InteligentesRed de Universidades con Carreras en Informática (RedUNCI

Multiple Revision on Horn Belief Bases

In logic programming, Horn clauses play a basic role, and in many logical constructs their consideration is important. In this paper we study the multiple revision of a belief base where the underlying logic is composed by Horn clauses. The main di culties as to restricting to the Horn fragment for revision operators by a single sentence are analyzed, and general results are presented about multiple revision operators on belief bases. We de ne prioritized multiple revision operators under a more restricted logic than classical propositional logic, i.e. Horn logic. We propose a set of postulates and representation theorems for each operation. This work is relevant for multiple revision in areas that employ Horn clauses, such as logic programming and deductive databases applications.XVII Workshop Agentes y Sistemas Inteligentes (WASI).Red de Universidades con Carreras en Informática (RedUNCI