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It is increasingly clear that Alzheimer's Disease (AD) presents with a strong genetic component. Recent Genome Wide Association Studies (GWAS) uncovered a huge number of polymorphisms associated with the disease which cumulative effect can be captured by the calculation of the polygenic risk score (PRS). PRS allows the identification of those at the highest and lowest risk of disease, opening new avenues for the understanding of the neurodegenerative processes and protective mechanisms. Samples collected from individuals identified at the extremes of the score can be used to generate stem cells models to investigate molecular mechanisms of the disease on the induced pluripotent stem cell (iPSC)-derived models such as microglial-like cells. In the first part of this study, a cohort of cryopreserved peripheral blood mononuclear cells (PBMC) samples collected from individuals originally sampled for GWAS and identified to have with high or low PRS for AD were used. These samples, collected more than 10 years ago resulted to have suboptimal quality, requiring several protocols and attempts to recover viability and cell number. One of these methods resulted in the successful reprogramming of several samples into iPSCs and their extensively characterisation. One of the most interesting discovery of recent GWAS is the novel R522 variant located in the PLCG2 gene which encode for the phospholipase Cγ2 enzyme, mainly expressed in microglia cells. To set the ground for functional studies, two different iPSCs-derived microglia differentiation protocols were tested and characterisations were carried out. Moreover, phenotypic characterization of iPSCs-derived cortical neurons and astrocytes were completed. iPSCs derived cortical neurons were used to established neuronal-microglia co-culture system; iPSCs-derived astrocyte were used to prepare the astrocyte-conditioned medium (ACM) used to feed cells. PLCγ2 R522 variant has been associated with decreased risk of developing late onset AD, and it represents the first classically drug-targetable vi molecule identified in LOAD genetic studies. Results of this study show that a model of iPSCs-derived microglia-like cells harbouring the PLCG2R522 SNP displays an altered neuroinflammatory response upon several different stimuli, such as LPS, oAβ, zymosan and ATP/ADP, in comparison to the common PLCG2P522 variant. Different outputs were analysed , including the secretion of cytokines (IL-6, TNF, GCSF, IL10), the possible involvement of NLRP3 inflammasome (IL1β), the levels of NO and the calcium response. Taken together the results support the hypothesis of a protective role of PLCγ2R522 variant in the context of AD, via reducing the neuro inflammatory burden in response to several stimuli.

In recent decades, improvements in power electronics have led to a significant spread of grid-connected converters, both for AC and DC applications. These converters are often interconnected together into a complex, typically non-linear power system, where the interaction between harmonics at the various interfaces of the network can lead to unstable operation mode. Hence, the development of methods in order to perform stability analysis of power systems has been a challenging topic for researchers. The analysis of DC and balanced three-phase AC systems has been widely studied and precise methods have been developed. However, in the case of single-phase or unbalanced three-phase systems, the analysis is more complex and at the beginning of this project it was still an open field for research. Thus, with focus on the latter systems, this thesis presents the stability analysis approach derived in the Linear Time Periodic (LTP) framework. Given a general power system, this is split into a source and a load subsystem. At the point of common coupling, small-signal current injections are performed in order to measure the harmonic matrix impedances of source and load. Then, LTP Nyquist Criterion is applied to the ratio of the two harmonic impedances. This allows one to perform stability analysis of any system, without the requirement of knowing its structure or its parameter values. Hence this can be referred to as a "black-box approach". Furthermore, in order to provide a theoretical validation of the method, several systems have been analysed and their LTP models have been analytically calculated and validated through simulation and experimental results. The harmonic impedances have been experimentally measured using a so-called Stability-Measurement-Unit (SMU), which is an independent converter that performs small-signal current injections and records voltage and currents perturbations. The recorded data has been post-processed in Matlab to calculate harmonic impedances and LTP Nyquist. A precise stability boundaries identification has been obtained for all the analysed systems.

This thesis principally aimed to investigate the precise role of IU in the development and maintenance of social anxiety and the relationship between IU, social anxiety and alcohol use. Furthermore, most of the findings of this thesis are original. A development and factor analyses of the Newcastle Substance Use Questionnaire (NSUQ), four independent cross-sectional studies and an experimental study were conducted. Non-clinical samples were recruited and entire studies were conducted online. The UK student sample study (university students; N = 349), the Indonesian study (N = 540) and also the replication of the UK student sample study (N = 200) reported that IU, FNE and AS each consistently made significant additive and unique contributions to the variance in social anxiety. The UK mixed sample study (N = 112) reported that both IU and FNE each made significant contributions, whilst shame did not. All the UK studies reported that IU contribution was the second greatest; whereas from the Indonesian study, the contribution of IU was the smallest. Each reported that the contribution of FNE was the greatest. Both the UK mixed sample and the UK student sample studies found that the effect of IU on social anxiety was significant only when FNE was intermediate to high. As FNE increased, the effect of IU in predicting social anxiety became stronger. The reversed analysis in the UK mixed sample study found that the effect of FNE on social anxiety was significant only when IU was intermediate to high, whereas in the UK student sample study it was significant at all levels of IU. Both studies reported that the effect of FNE on social anxiety became stronger as IU increased. The UK student sample study also reported that the effect of IU on social anxiety was significant at all levels of AS and it was augmented as the increasing of AS levels, whereas the effect of AS on social anxiety was significant only when IU was intermediate to high and it was augmented as the increasing the levels of IU. Moreover, the UK and Indonesian studies reported that FNE, IU and AS each consistently contributed to the variance in worry and depression symptoms. The UK study also found that the effects of IU on worry were significant at all levels of FNE or only when AS was low to high. The increase in FNE or AS decreased the impact of IU on worry. The reversed analyses found that the effects of either FNE or AS on worry were significant only when IU was low to high. Their effects became negative as IU increased. Furthermore, the experimental study (university students from the UK; N = 164) found that situational IU caused social anxiety and safety behaviours in the social interaction situation, although not in the social performance situation. It also provided evidence of x temporal precedence concerning the IU predisposition on safety behaviours in social interaction situation. It also provides evidence that the FNE predisposition influenced social anxiety and safety behaviours, in both situations. Unexpectedly, situational FNE was not effectively manipulated to cause social anxiety and safety behaviours. The factor analyses (participants of the UK student sample study; N = 285) reported that the three-factor solution of the alcohol section of the NSUQ was superior to other solutions and also interpretable. Social factor accounted for the most variance, followed by cognitive factor and lastly, sexual factor. Improving social interaction attained the highest rate and drinking alcohol with friends is the most frequent context. The UK student sample study and the replication also investigated the relationship between IU, social anxiety, social motives and alcohol use with friends. Both studies reported that the direct effects of IU, FNE and AS on drinking alcohol with friends were not significant. Moreover, the indirect effects of these cognitive vulnerabilities through social anxiety were significant and negative. Only the indirect effect of FNE through social motives was significant and positive. However, the indirect effect of IU through social anxiety and social motives serially was significant and positive, whereas the indirect effect of FNE was not significant. Overall, this thesis establishes the important role of IU, in conjunction with FNE and ASI, in predicting social anxiety; but also provides an initial evidence that IU may in fact have a causal role in social anxiety. Moreover, IU is a transdiagnostic factor which may underlie comorbidity across social anxiety and GAD. Lastly, this thesis reported that socially anxious students may be less inclined to participate in social activities and eventually less likely to take part in social drinking. However, they may be motivated by social reason to use alcohol as a social lubricant.

Efficacy of subcritical water in the recovery of the polyphenolic compounds from the apple pomace using a batch reactor system at 100-bar over a temperature range of 100-200oC for a residence time of 10–30 minutes was investigated. Organic solvent extractions using acetone and ethanol were carried out to serve as a baseline for comparison with the subcritical water extraction. Subcritical water was efficient in solubilising the apple pomace, and extracting polyphenolics with high antioxidant activity. Maximum solubilisation of the apple pomace was achieved at 145oC for 30 minutes and total phenolic content and antioxidant activity at 200oC. Solubilisation, ORAC activity and total phenolic content of subcritical water extract were 28.20g/100g DW, 99285μmol TE/g DW and 49.86mg/g GAE DW of apple pomace respectively, compared to 19.20g/100g DW, 6260.27 μmol TE/g DW and 21.70mg/g GAE DW of acetone extracts of apple pomace respectively. Protocatechuic aldehyde was identified for the first time only in the subcritical water extract and to date has not been identified in solvent extracts of cider apple pomace. Encapsulation of polyphenolic s of subcritical water extract using spray drying was explored. Particles/powders formed were derived from the naturally occurring carbohydrate polymers co-extracted with polyphenols. Addition of HPβ-Cyclodextrins (SWE+ HPβ-CD) to the directly encapsulated powder (SWE) significantly reduced hygroscopicity and improved antioxidant activity.

Research on physical activity and cognition is based on the existing theoretical and empirical evidence which indicates that engaging in cardiovascular exercise improves cognitive capabilities, by increasing neural functioning which improves learning (cognitive development). The question this research sought to answer was to determine whether or not (a) increased amounts of exercise improves cognitive recall and comprehension; and (b) there is a difference in cognitive "recall" and comprehension abilities when engaging in exercise occurs "before" a learning activity as compared to "after" a learning activity. This experimental pretest-posttest study examined whether or not a physical activity intervention improved community college students' "recall" and "comprehension" of recently learned information. The cardiovascular exercise intervention included two levels: moderate and light exercise. In one sequence the rehearsal of information (i.e., learning) took place "before" the students' engaged in exercise and in an alternate sequence, "after" the students have engaged in exercise. The results of the study demonstrated that performing a moderate amount of exercise "before" or "after" rehearsing for a "comprehension" test significantly improved test results. The moderate exercise group also scored higher on the "recall" posttest than the no exercise group, yet this difference was not found to be significant. Performing a light amount of exercise demonstrated improvement in comparison to not performing any exercise. Yet, this difference was not found to be significant. Overall, the results of the research demonstrated a significant positive linear trend between increased levels of physical activity and "comprehension". [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

In this thesis, Machine Learning (ML) and Deep Learning (DL) methods are used to identify aged cable locations in the power grid. An 18-manhole power grid model, composed of XLPE (cross-linked polyethylene) cables, was developed and simulated in the MATLAB Simulink environment. High-frequency impedance data of the cables was collected, from different locations in the power grid, to train the ML and DL algorithms. These ML and DL methods were used to identify possibly aged cables in the grid and pinpoint their location in the grid with 99% accuracy. The “best” measurement locations were identified using different ML methods. Moreover, it was found that only 2 to 3 measurements, out of 18 manholes in the grid, were enough to understand cable aging and the health condition of the cables along the grid.A “Long Transmission Line” model was used to model the characteristics of the XLPE cables. Both new and aged XLPE cables were also experimentally tested. Model parameters of both new and old cables were extracted using an iterative brute force method to match the actual impedance values with the values generated using the long transmission line model. Differences between the characteristics of new and aged cables were identified. The high frequency impedance of the cables was also recorded for varying cable lengths at varying high frequencies. For data collection purposes it was assumed that the 100 kHz impedance test equipment was installed in each manhole along the grid. During the course of this work, it was also found that only the injector block of the Active Clamp sensor was needed for data collection.

The holiness of the Church is one of the ecclesiological chapters that underwent great changes during the XXth century. This study deals with the contributions and changes on this theme related to the three major ideas of the Church in the period 1920-1965. The image of the mystical body of Christ provided important contents for the Holiness of the Church, some of which were assumed by authors who preferred to use other paradigms in ecclesiology. For this reason, we decided not to indicate the typical reasons and themes of a given paradigm, and have underlined changes of meaning when addressing the reception of arguments that were developed under another paradigm.

En los primeros tteinta afios del siglo XX la vida de la Iglesia va por delante de la eclesiologfa indicdndole retos. Sefialamos tres dreas importantes pata la santidad de la Iglesia: la reflexidn teoldgica sobte la parte activa de los laicos en la misidn de la Iglesia, el movimiento litiitgico, y la valoracidn del modo en que toda la Iglesia da testimonio de Cristo. La segunda patte propone una lectura mds abierta de los cambios de paradigma (del cuerpo mfstico de Cristo al pueblo de Dios). La visión histórico-salvífica ayudó a comprender que la santidad de la Iglesia in via aún no es perfecta, y que no debe entenderse sdlo con relacidn a la trascendencia.

Reseña del libro de José CAPMANY (et al), La Chiesa, Mistero di Comunione per la Missione: un contributo teológico e pastorale, Urbaniana University Press, Roma 1997, 225 p.