Expression and cellular localization of Copper transporter 2 (Ctr2) in Mus musculus

The Ctr family is an essential part of the copper homeostasis machinery and its members share sequence homology and structural and functional features. Higher eukaryotes express two members of this family Ctr1 and Ctr2. Numerous structural and functional studies are available for Ctr1, the only high affinity Cu(I) transporter thus far identified. Ctr1 holigotrimers mediate cellular copper uptake and this protein was demonstrated to be essential for embryonic development and to play a crucial role in dietary copper acquisition. Instead very little is known about Ctr2, it bears structural homology to the yeast vacuolar copper transporter, which mediates mobilization of vacuolar copper stores. Recent studies using over-expressed epitope-tagged forms of human Ctr2 suggested a function as a low affinity copper transporter that can mediate either copper uptake from the extracellular environment or mobilization of lysosomal copper stores. Using an antibody that recognizes endogenous mouse Ctr2, we studied the expression and localization of endogenous mouse Ctr2 in cell culture and in mouse models to understand its regulation and function in copper homeostasis. By immunoblot we observed a regulation of mCtr2 protein levels in a copper and Ctr1 dependent way. Our observations in cells and transgenic mice suggest that lack of Ctr1 induces a strong downregulation of Ctr2 probably by a post-translational mechanism. By indirect immunofluorescence we observed an exclusive intracellular localization in a perinuclear compartment and no co-localization with lysosomal markers. Immunofluorescence experiments in Ctr1 null cells, supported by sequence analysis, suggest that lysosomes may play a role in mCtr2 biology not as resident compartment, but as a degradation site. In appendix a LC-mass method for analysis of algal biotoxins belonging to the family of PsP (paralytic shellfish poisoning) is described.

Gold and the Stock Market: 3 Essays on Gold Investments

This thesis gives an overview of the history of gold per se, of gold as an investment good and offers some institutional details about gold and other precious metal markets. The goal of this study is to investigate the role of gold as a store of value and hedge against negative market movements in turbulent times. I investigate gold’s ability to act as a safe haven during periods of financial stress by employing instrumental variable techniques that allow for time varying conditional covariance. I find broad evidence supporting the view that gold acts as an anchor of stability during market downturns. During periods of high uncertainty and low stock market returns, gold tends to have higher than average excess returns. The effectiveness of gold as a safe haven is enhanced during periods of extreme crises: the largest peaks are observed during the global financial crises of 2007-2009 and, in particular, during the Lehman default (October 2008). A further goal of this thesis is to investigate whether gold provides protection from tail risk. I address the issue of asymmetric precious metal behavior conditioned to stock market performance and provide empirical evidence about the contribution of gold to a portfolio’s systematic skewness and kurtosis. I find that gold has positive coskewness with the market portfolio when the market is skewed to the left. Moreover, gold shows low cokurtosis with the market returns during volatile periods. I therefore show that gold is a desirable investment good to risk averse investors, since it tends to decrease the probability of experiencing extreme bad outcomes, and the magnitude of losses in case such events occur. Gold thus bears very important and under-researched characteristics as an asset class per se, which this thesis contributed to address and unveil.

La conservazione viva dell'esistente. Storia, progetto e restauro nell'opera di Josef Wiedemann

La tesi analizza, nel quadro del secondo dopoguerra, quattro casi studio scelti tra le opere di ricostruzione dell’architetto Josef Wiedemann (1910-2001) nel centro di Monaco di Baviera: Odeon (1951-1952), Alte Akademie (1951-1955), Siegestor (1956-1958) e Glyptothek (1961-1972). L’architetto si occupa di opere simbolo della città di Monaco, affrontando la loro ricostruzione come un tema fondante per la storia e l’identità del popolo bavarese, ma soprattutto come un’occasione per definire un metodo d’intervento sulle rovine della guerra. Il suo lavoro è caratterizzato infatti per la ricerca costante di una sintesi tra interesse per la conservazione dell’antico e apertura al nuovo; ispirandosi all’insegnamento del maestro Hans Döllgast, Wiedemann traccia una nuova originale strada per l’intervento sull’antico, segnata da una profonda capacità tecnico-progettuale e dall'attenzione alle nuove esigenze a cui deve rispondere un’architettura contemporanea. Partendo dai suoi scritti e dalle sue opere, si può rilevare un percorso coerente che, partendo dalla conoscenza della storia dell'edificio, ripercorrendone l’evoluzione dallo stato che potremmo definire “originario” allo stato di rovina, giunge a produrre nel progetto realizzato una sintesi tra il passato e il futuro. L'architetto, nella visione di Wiedemann, è chiamato a un compito di grande responsabilità: conoscere per progettare (o ri-progettare) un edificio che porta impressi su di sé i segni della propria storia. Nel metodo che viene messo progressivamente a punto operando nel corpo vivo dei monumenti feriti dalla guerra, è percepibile fino a distinguerlo chiaramente l’interesse e l’influenza del dibattito italiano sul restauro. La conservazione “viva” dell'esistente, così come viene definita da Wiedemann stesso, si declina in modo diverso per ogni caso particolare, approdando a risultati differenti tra loro, ma che hanno in comune alcuni principi fondamentali: conoscere, ricordare, conservare e innovare.

Identity dynamics and the emergence of new organizational arrangements: A multi-level study

Organizational and institutional scholars have advocated the need to examine how processes originating at an individual level can change organizations or even create new organizational arrangements able to affect institutional dynamics (Chreim et al., 2007; Powell & Colyvas, 2008; Smets et al., 2012). Conversely, research on identity work has mainly investigated the different ways individuals can modify the boundaries of their work in actual occupations, thus paying particular attention to ‘internal’ self-crafting (e.g. Wrzesniewski & Dutton, 2001). Drawing from literatures on possible and alternative self and on positive organizational scholarship (e.g., Obodaru, 2012; Roberts & Dutton, 2009), my argument is that individuals’ identity work can go well beyond the boundaries of internal self-crafting to the creation of new organizational arrangements. In this contribution I analyze, through multiple case studies, healthcare professionals who spontaneously participated in the creation of new organizational arrangements, namely health structures called Community Hospitals. The contribution develops this form of identity work by building a grounded model. My findings disclose the process that leads from the search for the enactment of different self-concepts to positive identities, through the creation of a new organizational arrangement. I contend that this is a particularly complex form of collective identity work because it requires, to be successful, concerted actions of several internal, external and institutional actors, and it also requires balanced tensions that – at the same time - enable individuals’ aspirations and organizational equilibrium. I name this process organizational collective crafting. Moreover I inquire the role of context in supporting the triggering power of those unrealized selves. I contribute to the comprehension of the consequences of self-comparisons, organizational identity variance, and positive identity. The study bears important insights on how identity work originating from individuals can influence organizational outcomes and larger social systems.

Experimental assessment of environmental decay effects in masonry via non destructive diagnostic techniques and mechanical tests

Environmental decay in porous masonry materials, such as brick and mortar, is a widespread problem concerning both new and historic masonry structures. The decay mechanisms are quite complex dependng upon several interconnected parameters and from the interaction with the specific micro-climate. Materials undergo aesthetical and substantial changes in character but while many studies have been carried out, the mechanical aspect has been largely understudied while it bears true importance from the structural viewpoint. A quantitative assessment of the masonry material degradation and how it affects the load-bearing capacity of masonry structures appears missing. The research work carried out, limiting the attention to brick masonry addresses this issue through an experimental laboratory approach via different integrated testing procedures, both non-destructive and mechanical, together with monitoring methods. Attention was focused on transport of moisture and salts and on the damaging effects caused by the crystallization of two different salts, sodium chloride and sodium sulphate. Many series of masonry specimens, very different in size and purposes were used to track the damage process since its beginning and to monitor its evolution over a number of years Athe same time suitable testing techniques, non-destructive, mini-invasive, analytical, of monitoring, were validated for these purposes. The specimens were exposed to different aggressive agents (in terms of type of salt, of brine concentration, of artificial vs. open-air natural ageing, …), tested by different means (qualitative vs. quantitative, non destructive vs. mechanical testing, punctual vs. wide areas, …), and had different size (1-, 2-, 3-header thick walls, full-scale walls vs. small size specimens, brick columns and triplets vs. small walls, masonry specimens vs. single units of brick and mortar prisms, …). Different advanced testing methods and novel monitoring techniques were applied in an integrated holistic approach, for quantitative assessment of masonry health state.