An equilibrium approach to modelling social interaction

The aim of this work is to put forward a statistical mechanics theory of social interaction, generalizing econometric discrete choice models. After showing the formal equivalence linking econometric multinomial logit models to equilibrium statical mechanics, a multi- population generalization of the Curie-Weiss model for ferromagnets is considered as a starting point in developing a model capable of describing sudden shifts in aggregate human behaviour. Existence of the thermodynamic limit for the model is shown by an asymptotic sub-additivity method and factorization of correlation functions is proved almost everywhere. The exact solution for the model is provided in the thermodynamical limit by nding converging upper and lower bounds for the system's pressure, and the solution is used to prove an analytic result regarding the number of possible equilibrium states of a two-population system. The work stresses the importance of linking regimes predicted by the model to real phenomena, and to this end it proposes two possible procedures to estimate the model's parameters starting from micro-level data. These are applied to three case studies based on census type data: though these studies are found to be ultimately inconclusive on an empirical level, considerations are drawn that encourage further refinements of the chosen modelling approach, to be considered in future work.

Genetica molecolare dell'autismo: studi di associazione ed analisi di geni candidati

Autism is a neurodevelpmental disorder characterized by impaired verbal communication, limited reciprocal social interaction, restricted interests and repetitive behaviours. Twin and family studies indicate a large genetic contribution to ASDs (Autism Spectrum Disorders). During my Ph.D. I have been involved in several projects in which I used different genetic approaches in order to identify susceptibility genes in autism on chromosomes 2, 7 and X: 1)High-density SNP association and CNV analysis of two Autism Susceptibility Loci. The International Molecular Genetic Study of Autism Consortium (IMGSAC) previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we evaluated the patterns of linkage disequilibrium (LD) and the distribution of haplotype blocks, utilising data from the HapMap project, across the two strongest peaks of linkage on chromosome 2 and 7. More than 3000 SNPs have been selected in each locus in all known genes, as well as SNPs in non-genic highly conserved sequences. All markers have been genotyped to perform a high-density association analysis and to explore copy number variation within these regions. The study sample consisted of 127 and 126 multiplex families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Association and CNV analysis implicated several new genes, including IMMP2L and DOCK4 on chromosome 7 and ZNF533 and NOSTRIN on the chromosome 2. Particularly, my contribution to this project focused on the characterization of the best candidate gene in each locus: On the AUTS5 locus I carried out a transcript study of ZNF533 in different human tissues to verify which isoforms and start exons were expressed. High transcript variability and a new exon, never described before, has been identified in this analysis. Furthermore, I selected 31 probands for the risk haplotype and performed a mutation screen of all known exons in order to identify novel coding variants associated to autism. On the AUTS1 locus a duplication was detected in one multiplex family that was transmitted from father to an affected son. This duplication interrupts two genes: IMMP2L and DOCK4 and warranted further analysis. Thus, I performed a screening of the cohort of IMGSAC collection (285 multiplex families), using a QMPSF assay (Quantitative Multiplex PCR of Short fluorescent Fragments) to analyse if CNVs in this genic region segregate with autism phenotype and compare their frequency with a sample of 475 UK controls. Evidence for a role of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family. 2)Analysis of X chromosome inactivation. Skewed X chromosome inactivation (XCI) is observed in females carrying gene mutations involved in several X-linked syndromes. We aimed to estimate the role of X-linked genes in ASD susceptibility by ascertaining the XCI pattern in a sample of 543 informative mothers of children with ASD and in a sample of 164 affected girls. The study sample included families from different european consortia. I analysed the XCI inactivation pattern in a sample of italian mothers from singletons families with ASD and also a control groups (144 adult females and 40 young females). We observed no significant excess of skewed XCI in families with ASD. Interestingly, two mothers and one girl carrying known mutations in X-linked genes (NLGN3, ATRX, MECP2) showed highly skewed XCI, suggesting that ascertainment of XCI could reveal families with X-linked mutations. Linkage analysis was carried out in the subgroup of multiplex families with skewed XCI (≥80:20) and a modest increased allele sharing was obtained in the Xq27-Xq28 region, with a peak Z score of 1.75 close to rs719489. In this region FMR1 and MECP2 have been associated in some cases with austim and therefore represent candidates for the disorder. I performed a mutation screen of MECP2 in 33 unrelated probands from IMGSAC and italian families, showing XCI skewness. Recently, Xq28 duplications including MECP2, have been identified in families with MR, with asymptomatic carrier females showing extreme (>85%) skewing of XCI. For these reason I used the sample of probands from X-skewed families to perform CNV analysis by Real-time quantitative PCR. No duplications have been found in our sample. I have also confirmed all data using as alternative method the MLPA assay (Multiplex Ligation dependent Probe Amplification). 3)ASMT as functional candidate gene for autism. Recently, a possible involvement of the acetylserotonin O-methyltransferase (ASMT) gene in susceptibility to ASDs has been reported: mutation screening of the ASMT gene in 250 individuals from the PARIS collection revealed several rare variants with a likely functional role; Moreover, significant association was reported for two SNPs (rs4446909 and rs5989681) located in one of the two alternative promoters of the gene. To further investigate these findings, I carried out a replication study using a sample of 263 affected individuals from the IMGSAC collection and 390 control individuals. Several rare mutations were identified, including the splice site mutation IVS5+2T>C and the L326F substitution previously reported by Melke et al (2007), but the same rare variants have been found also in control individuals in our study. Interestingly, a new R319X stop mutation was found in a single autism proband of Italian origin and is absent from the entire control sample. Furthermore, no replication has been found in our case-control study typing the SNPs on the ASMT promoter B.

Designing and Programming Organizational Infrastructures for Agents situated in Artifact-based Environments

Actual trends in software development are pushing the need to face a multiplicity of diverse activities and interaction styles characterizing complex and distributed application domains, in such a way that the resulting dynamics exhibits some grade of order, i.e. in terms of evolution of the system and desired equilibrium. Autonomous agents and Multiagent Systems are argued in literature as one of the most immediate approaches for describing such a kind of challenges. Actually, agent research seems to converge towards the definition of renewed abstraction tools aimed at better capturing the new demands of open systems. Besides agents, which are assumed as autonomous entities purposing a series of design objectives, Multiagent Systems account new notions as first-class entities, aimed, above all, at modeling institutional/organizational entities, placed for normative regulation, interaction and teamwork management, as well as environmental entities, placed as resources to further support and regulate agent work. The starting point of this thesis is recognizing that both organizations and environments can be rooted in a unifying perspective. Whereas recent research in agent systems seems to account a set of diverse approaches to specifically face with at least one aspect within the above mentioned, this work aims at proposing a unifying approach where both agents and their organizations can be straightforwardly situated in properly designed working environments. In this line, this work pursues reconciliation of environments with sociality, social interaction with environment based interaction, environmental resources with organizational functionalities with the aim to smoothly integrate the various aspects of complex and situated organizations in a coherent programming approach. Rooted in Agents and Artifacts (A&A) meta-model, which has been recently introduced both in the context of agent oriented software engineering and programming, the thesis promotes the notion of Embodied Organizations, characterized by computational infrastructures attaining a seamless integration between agents, organizations and environmental entities.

Prematurità: Interazioni Precoci e Sintomatologia Materna

La prematurità rappresenta un fattore di rischio per la qualità delle interazioni precoci e la sintomatologia materna, soprattutto in caso di nascita VLBW (peso ≤ 1500 grammi) ed ELBW (≤1000 grammi). Scopo dello studio è valutare a 3 e 9 mesi di età corretta le modalità interattive delle diadi madre-bambino e lo stato affettivo materno in due campioni di prematuri, ELBW e VLBW, confrontandoli con un gruppo di bambini nati a termine (GC). Un campione di 119 diadi madre-bambino, di cui 71 nati prematuri (30 VLBW e 21 ELBW) e 68 a termine, sono stati valutati all'età di 3 e 9 mesi. Durante gli assessment, è avvenuta la videoregistrazione dell’interazione madre-bambino, codificata mediante le Global Rating Scales (a 3 mesi) ed il CARE Index Infant (a 9 mesi), e la valutazione della sintomatologia materna, attraverso Edinburgh Postnatal Depression Scale, Penn State Worry Questionnaire, Social Interaction and Anxiety Scale, Social Phobia Scale, Parenting Stress Index-Short Form, Questionari italiani del Temperamento. A 3 mesi, le madri di ELBW appaiono più demanding e meno sensibili rispetto a quelle di VLBW; più intrusive rispetto a quelle di GC. Tali madri, inoltre, sono significativamente meno sensibili di quelle del GC anche a 9 mesi. In entrambi gli assessment, tali madri presentano livelli significativamente maggiori di depressione, ansia generalizzata e stress, rispetto a quelle di entrambi gli altri gruppi. Non emergono differenze rispetto all'ansia sociale nè alla percezione del temperamento. Le analisi della correlazione hanno evidenziato specifiche relazioni tra la sintomatologia materna e i pattern interattivi nei tre gruppi. La nascita pretermine rappresenta un fattore di rischio solo per le madri di ELBW, che presentano difficoltà interattive ed elevata sintomatologia; quelle dei VLBW, infatti, tendono a presentare pattern interattivi affini a quelle del GC, mostrando adeguata sensibilità e bassi livelli di depressione, ansia e stress.

Plasticity in body and peripersonal space representations

A successful interaction with objects in the environment requires integrating information concerning object-location with the shape, dimension and position of body parts in space. The former information is coded in a multisensory representation of the space around the body, i.e. peripersonal space (PPS), whereas the latter is enabled by an online, constantly updated, action-orientated multisensory representation of the body (BR) that is critical for action. One of the critical features of these representations is that both PPS and BR are not fixed, but they dynamically change depending on different types of experience. In a series of experiment, I studied plastic properties of PPS and BR in humans. I have developed a series of methods to measure the boundaries of PPS representation (Chapter 4), to study its neural correlates (Chapter 3) and to assess BRs. These tasks have been used to study changes in PPS and BR following tool-use (Chapter 5), multisensory stimulation (Chapter 6), amputation and prosthesis implantation (Chapter 7) or social interaction (Chapter 8). I found that changes in the function (tool-use) and the structure (amputation and prosthesis implantation) of the physical body elongate or shrink both PPS and BR. Social context and social interaction also shape PPS representation. Such high degree of plasticity suggests that our sense of body in space is not given at once, but it is constantly constructed and adapted through experience.