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Silicon photomultipliers: characterization and application to fluorescence flucturation spectroscopy.
No full textThis thesis originates from and develops around Silicon Photomultipliers (SiPMs): starting from a description of the working principles of these devices, this work presents a review on this technology and on some of its possible applications.
The great part of this work took place within the framework of an international scientific and industrial collaboration (RAPSODI1, a project funded by the European Commetee), with the aim of developing three radiation detectors using the SiPM technology; in order to find the optimal sensor for each application, an exhaustive protocol to provide a characterization of the performances of the main SiPM parameters (gain, photo-detection efficiency, dark count rate, optical cross-talk, breakdown voltage dependence from temperature) has been provided.
In order to further improve the knowledge on Silicon PhotoMultipliers, a phenomenological model describing the statistics of Geiger-Müller avalanches for impinging photons with known probability distribution has been elaborated: this model takes into account the contribution given by the thermally generated avalanches and by the cross-talk, thus providing a model for the SiPM deviations from the ideal bernoullian detection.
Last, a feasibility study on the possibility of using this sensors as detecting technology in Fluorescence Fluctuation Spectroscopy (FFS) biophysical experiments had been conducted. In FFS experiments the parameters describing the system under study (proteins ligated with fluorophores in a solution) are measured from the deviations of the fluorescence intensity around its mean value: the use of fast (with a sub-nanosecond temporal resolution) detectors with an large photon number resolution can costitute an improvement of the experimental conditions. Thus a dedicated setup had been commissioned and SiPMs demonstrated to be able to perform an effective Photon Counting Histogram (one of the FFS techniques) measurement.
1RAdiation Protection with Silicon Optoelectronic Devices and Instruments – COOP 3299
Categorical algebras for the compositional construction of probabilistic and distributed systems.
No full textStructured transition systems have been widely used in the formal specification of computing systems, including concurrent and probabilistic systems. In this thesis we extend the span of graphs algebra introduced in [40] to describe concurrent systems in a compositional way, in order to model probabilistic distributed systems.
The span algebra of [40] may be regarded as an extension of various automata models of computation based on distributed automata. With the introduction of both parallel and sequential operations, this extension allows the compositional description of concurrent, distributed and mobile systems. An important aspect of span graph model is that there is also a geometric characterization associated with the algebra along the lines of Penrose’s algebra of tensors.
The algebra of transition systems we describe is a well-supported compact closed category - a symmetric monoidal category for which every object has a separable algebra structure (satisfying Frobenius equation) - whose arrows are automata in which the actions have probabilities. The operations of the category permit the compositional description of probabilistic processes and in particular of classical finite Markov chains. The systems we can model with our algebra are distributed, hierarchical and with an evolving geometry.
We also extend the span algebra of [40] in order to permit the inclusion of quantum components. Again, this algebra is a well-supported compact closed category. This extension permits a compositional description of quantum protocols, in which quantum components interact with classical finite state components. In our view, the inclusion of explicit components of finite state classical control adds conceptual clarity and precision to quantum protocols
Temporal and spatial dynamics of organic chemicals in the environment with a multimedia fate model.
No full textIn this PhD thesis we have deal with different aspects of treatment and pathogenesis of diabetes mellitus. With regard to type 1 diabetes, we followed three different research lines clarifying aspects not yet well known on different types of patient transplants. Regarding type 2 diabetes, we studied the role of insular amyloid in the development and progression of the disease.
Transplantation is one of the possible therapies for type 1 diabetes and can be performed in patients who no longer respond to insulin therapy in satisfactory manner. For type 1 diabetes treatment there are three possible types of transplantation:
• Pancreas, often associated with kidney transplantation, is the only treatment for type 1 diabetes that can maintain long-term insulin independence and normoglycemia. In type 1 diabetes patients, chronic hyperglycemia leads to both microvascular and macrovascular damages probably due to overproduction of superoxides by the mitochondrial electron transport chain. In patients subjected to pancreas transplantation, it has been noted improvements in the microcirculation and in particular at the level of endothelial cells. In order to identify possible mechanisms by which transplantation improves microcirculation, we analyzed the expression of proteins involved in cellular response to oxidative stress in skin biopsies. According to the results obtained in our studies, some of the identified proteins may be considered as therapeutic targets for a new class of drugs, potentially able to correct cell modifications in cases where normoglycemia cannot be restored.
• Human purified pancreatic islet transplantation. The transplantation of human islets can successfully restore long-term insulin independence and improve glycemic control. However, the number of patients that remain insulin-independent decreases gradually in 2-3 years. Several hypotheses have been formulated in order to explain this negative response. One hypothesis is the “functional exhaustion" of a chronically overstimolated β cells mass. To better understand this possible mechanism, we studied at morphological, immunohistochemical and ultrastructural level the pancreatic islets before and after human islet cells transplantation in athymic nude mice made diabetic.
• Stem cell transplantation. Stem cells seem to be the new frontier for the treatment of type 1 diabetes. Several stem cell types have been identified as potential progenitors of pancreatic β cells and mesenchymal stem cells (MSC) seem to be a possible source of them. In addition, MSCs have immunomodulatory effects as demonstrated in several researches in which these cells have been used to reduce
the burden of a variety of immune-mediated diseases. Since type 1 diabetes is an autoimmune disorder, we explored the possibility to use MSCs transplantation as a therapeutic approach. For this reason, we characterized MSCs obtained from diabetes susceptible (NOD) mice and from diabetes-resistant (BALB/c) mice. After, we injected MSCs into pre-diabetic NOD mice and we evaluated their immunomodulatory effects in vivo.
It has been demonstrated that amyloid deposits are one of the main morphological alteration of the islets of Langerhans in patients affects by long-standing type 2 diabetes. Typically, islet amyloid derives from deposition of amylin which is synthesized and stored in pancreatic β cells together with insulin. Amylin is produced as a pro-peptide and cut by specific proteases. It has been showed in Alzheimer's patients that the protease BACE 1 is involved in amyloid plaques production. In addition, a BACE 1 homologue called BACE 2 has been identified and localised in most adult tissues such as the pancreatic one. However, the role of BACE 2 still remains unclear. By using immunohistochemical, ultrastructural and immunocytochemical techniques, we identified and localised BACE 2 in secretory granules of mice and rats pancreatic β cells. The data collected in our studies could be considered as a starting point for further investigations on human normal and diabetic pancreases. For instance, the correlation between BACE 2 expression and amyloid deposition could help to better understand a possible role of BACE 2 in islet amyloidosis and consequently could improve our understanding of the type 2 diabetes disorder.
However, it is not yet clear if amyloidosis is a primary or secondary event in the pathogenesis of diabetes. In order to better understand this situation, we used the Papio hamadryas (baboon) as an in vivo model. Indeed, baboons spontaneously develop type 2 diabetes associated with obesity as in humans, hypothesizing a similarity in diabetes pathogenesis between the two species. Our results strongly support that the insular amyloidosis associated with β cell apoptosis, α cell proliferation and hypertrophy are determinants of islets dysfunctional remodeling and hyperglycemia in baboons. In addition, our studies allow to hypothise a correlation between severity of amyloidosis, age and fasting plasma glucose levels
Temporal and spatial dynamics of organic chemicals in the environment with a multimedia fate model.
No full textOnce chemicals are released into the environment, their environmental fate is determined by their usage and discharge, partitioning tendencies, and by transport and transformation processes, which may vary greatly in space and time. In the last three decades, an increasing number of models based on the concept of “communicating media” have been developed to understand and predict the fate of chemicals in the environment. The tendency emerging from recent experimental and modelling efforts is to consider the fate of chemicals more closely related to the dynamics characterizing the “environmental scenario”. This thesis aims to give a contribution to the investigation of the role played by temporal and spatial dynamics of key chemodynamic processes and environmental properties in influencing the fate of chemicals in the environment. The focus of the thesis was the development of a new, dynamic and site specific multimedia fate model (MFM) of organic chemicals in the air-soil system. The model, named SoilPlus, is described in Chapter 1 and includes two dynamic air compartments, a multicompartmental litter, acting as an “intermediate” compartment between the air and a multicompartmental soil. The model also performs a complete water balance, accounting also for dissolved organic carbon (DOC) fluxes in the litter/soil system. The model underwent a process of benchmarking and then was used to investigate the role of the litter as a buffer compartment between soil and air, modelling hexachlorobenzene as an example of persistent organic pollutant (POP). SoilPlus uses the same two air compartments developed for the AirFug model, described in Chapter 2. AirFug integrates a new MFM, characterized by two dynamic-air compartments and a single soil compartment, and a meteorological preprocessor; after the model benchmarking, it was evaluated against experimental data from the literature regarding diel (less than 24 hours) variations of PCBs concentrations in urban air. The process of development of these two models prompted to investigate a suitable numerical solution for the equation system describing the chemical mass balance. Chapter 3 is focused on a critical evaluation of the performance of three different numerical methods suitable for models based on adjacent compartments. One of the tested methods was then implemented in the spatial-explicit version of SoilPlus developed and described in Chapter 4. This version of the model was applied to a geographic explicit scenario (a small agricultural basin) for which measured concentrations of pesticides in water were available, in order to evaluate the benefits arising from considering a more spatially resolved scenario (up to the field-scale) on the calculation of environmental concentrations.
Chapter 5, finally, summarizes the results of a recent workshop held at the University of Lancaster in 2009 focused on the need to consider cross-fertilization between the POP-cycle and C-cycle communities in order to more accurately predict future exposure scenarios for POPs
Role of UDP-GlcNAc and hyaluronan synthase 2 O-GlcNAcylation in the control of hyaluronan synthesis.
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Novel mechanisms in the modulation of D-serine cellular concentration: hDAAO-pLG72 interaction
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Nonomuraea sp. ATCC 39727 a rare actinomycete producing the glycopeptide A40926: mechanism of self resistance.
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Stress ossidativo ed infiammazione contribuiscono alla disfunzione vascolare in un modello murino di sindrome metabolica.
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Transition metal catalyzed reactions on allenic substrates for heterocyclic synthesis.
No full textThe main subject of this thesis are transition metal catalyzed reactions onto allenic substrates. The reactivity of allenic double bonds in presence or absence of transition metal was investigated and studied in order to favor intramolecular processes able to yield nitrogen-containing heterocyclic structures. We investigated the feasibility of cyclization processes onto allenamides that could have been built starting from α-aminoacids, that is, with a pre-introduced chiral information in the starting materials able to be kept till the obtainment of the final enantiopure products. At first we developed a procedure for building monocyclic five- and six-membered nitrogen containing heterocycles from under basic conditions. Next, we studied the Pd-catalyzed nitrogen addition onto the -carbon of the aforementioned allenes in order to obtain imidazolidinones structures, that are of great interest for organic chemists. Although the transition metal-catalyzed generation of heterocyclic compounds via reactions between allene bearing a nucleophilic functionality and organic halides is well established, such a strategy has never been applied to allenamides. Thus, we set up conditions for a synthesis of 2-styryl-imidazolidinone structures through a pure domino carbopalladation-amination sequence. The same protocol, under CO atmosphere, was able to lead to interesting enone structures, while the incorporation of an iodine atom in an appropriate position into the starting allenamides permitted to access imidazoisoquinolinones.
The second part of this thesis was spent in the laboratories of Prof. Giovanni Poli (Univ. Pierre et Marie Curie, Paris), where a new approach to 1,4-benzodiazepin-5-ones via a pure domino carbopalladation /allylic amination process starting from allenylamides of anthranilic acid was developed. The cyclization step is quite different from the previously described one, since the originality of this protocols lies in the fact that no phosphines as ligands are needed, as the Pd- species is stabilized by the conjoint action of BuLi and DMSO.
The shorter homologues of these allenylamides were the next substrate which we focused our attention. Submitted to the same protocol, they indeed gave rise to quinazolinone structures. However, a gold-catalyzed cyclization set up onto the same substrates was much more interesting, due to its ability to lead to vinyl-substituted products. Finally, the same products can be obtained through the first example of ruthenium catalyzed intramolecular hydroamination of allenes, though this reactions still needs to be investigated for its mechanism and scope
