A panchromatic study of stellar populations in Galactic Globular Clusters

The aim of this Thesis is to investigate (i) how common the bimodal Blue Straggler Stars (BSS) radial distribution is in stellar clusters and (ii) which are the physical processes that can produce this bimodality. We discuss possible relations between the properties of the BSS radial distribution and the dynamical state of the hosting clusters by making use of dynamical models and simulations. When relevant, we also discuss the possible links with some cluster "anomalies" and the effects of a massive object (like Imtermediate Mass Black Hole) in the cluster center. To this purpose we present the observational multiwavelength studies of the BSS populations and their radial distributions in 5 GGCs: M5, M55, M2, NGC 2419 and NGC 6388.

Study on the regulation of mRNA expression of GABA transporters (GAT-1 and GAT-3) in rat brain

The submitted work concentrated on the study of mRNA expression of two distinct GABA transporters, GAT-1 and GAT-3, in the rat brain. For the detection and quantification of the chosen mRNAs, appropriate methods had to be established. Two methods, ribonuclease protection assay (RPA) and competitive RT-PCR were emloyed in the present study. Competitive RT-PCR worked out to be 20 times more sensitive as RPA. Unlike the sensitivity, the fidelity of both techniques was comparable with respect to their intra- and inter-assay variability.The basal mRNA levels of GAT-1 and GAT-3 were measured in various brain regions. Messenger RNAs for both transporters were detected in all tested brain regions. Depending on the region, the observed mRNA level for GAT-1 was 100-300 higher than for GAT-3. The GAT-1 mRNA levels were similar in all tested regions. The distribution of GAT-3 mRNA seemed to be more region specific. The strongest GAT-3 mRNA expression was detected in striatum, medulla oblongata and thalamus. The lowest levels of GAT-3 were in cortex frontalis and cerebellum.Furthermore, the mRNA expression for GAT-1 and GAT-3 was analysed under altered physiological conditions; in kindling model of epilepsy and also after long-term treatment drugs modulating GABAergic transmission. In kindling model of epilepsy, altered GABA transporter function was hypothesised by During and coworkers (During et al., 1995) after observed decrease in binding of nipecotic acid, a GAT ligand, in hippocampus of kindled animals. In the present work, the mRNA levels were measured in hippocampus and whole brain samples. Neither GAT-1 nor GAT-3 showed altered transcription in any tested region of kindled animals compared to controls. This leads to conclusion that an altered functionality of GABA transporters is involved in epilepsy rather than a change in their expression.The levels of GAT-1 and GAT-3 mRNAs were also measured in the brain of rats chronically treated with diazepam or zolpidem, GABAA receptor agonists. Prior to the molecular biology tests, behavioural analysis was carried out with chronically and acutely treated animals. In two tests, open field and elevated plus-maze, the basal activity exploration and anxiety-like behaviour were analysed. Zolpidem treatment increased exploratory activity. There were observed no differencies between chronically and acutely treated animals. Diazepam increased exploratory activity and decresed anxiety-like behaviour when applied acutely. This effect disappeard after chronic administration of diazepam. The loss of effect suggested a development of tolerance to effects of diazepam following long-term administration. Double treatment, acute injection of diazepam after chronic diazepam treatment, confirmed development of a tolerance to effects of diazepam. Also, the mRNAs for GAT-1 and GAT-3 were analysed in cortex frontalis, hippocampus, cerebellum and whole brain samples of chronically treated animals. The mRNA levels for any of tested GABA transporters did not show significant changes in any of tested region neither after diazepam nor zolpidem treatment. Therefore, changes in GAT-1 and GAT-3 transcription are probably not involved in adaptation of GABAergic system to long-term benzodiazepine administration and so in development of tolerance to benzodiazepines.

Analysis of the nuclear properties of Brightest Cluster Galaxies and comparison with "normal" radio galaxies.

The aim of this PhD thesis is the study of the nuclear properties of radio loud AGN. Multiple and/or recent mergers in the host galaxy and/or the presence of cool core in galaxy clusters can play a role in the formation and evolution of the radio source. Being a unique class of objects (Lin & Mohr 2004), we focus on Brightest Cluster Galaxies (BCGs). We investigate their parsec scale radio emission with VLBI (Very Long Baseline Interferometer) observations. From literature or new data , we collect and analyse VLBA (Very Long Baseline) observations at 5 GHz of a complete sample of BCGs and ``normal'' radio galaxies (Bologna Complete Sample , BCS). Results on nuclear properties of BCGs are coming from the comparison with the results for the Bologna COmplete Sample (BCS). Our analysis finds a possible dichotomy between BCGs in cool-core clusters and those in non-cool-core clusters. Only one-sided BCGs have similar kinematic properties with FRIs. Furthermore, the dominance of two-sided jet structures only in cooling clusters suggests sub-relativistic jet velocities. The different jet properties can be related to a different jet origin or to the interaction with a different ISM. We larger discuss on possible explanation of this.

Cultura "Open" e nuovi modelli normativi per la gestione della conoscenza

L'obiettivo della ricerca è di compiere un'analisi dell'impatto della cosiddetta cultura "open" alla luce dell'attuale condizione del World Wide Web. Si prenderà in considerazione, in particolare, la genesi del movimento a partire dalle basi di cultura hacker e la relativa evoluzione nella filosofia del software libero, con il fine ultimo di identificare il ruolo attuale del modello open source nello scenario esistente. L'introduzione al concetto di Open Access completerà la ricerca anche considerando la recente riaffermazione della conoscenza come bene comune all'interno della Società dell'Informazione

Institutional Processes and Discursive Strategies: Rhetoric and Vocabulary Analysis of CSR and Sustainability

The candidate tackled an important issue in contemporary management: the role of CSR and Sustainability. The research proposal focused on a longitudinal and inductive research, directed to specify the evolution of CSR and contribute to the new institutional theory, in particular institutional work framework, and to the relation between institutions and discourse analysis. The documental analysis covers all the evolution of CSR, focusing also on a number of important networks and associations. Some of the methodologies employed in the thesis have been employed as a consequence of data analysis, in a truly inductive research process. The thesis is composed by two section. The first section mainly describes the research process and the analyses results. The candidates employed several research methods: a longitudinal content analysis of documents, a vocabulary research with statistical metrics as cluster analysis and factor analysis, a rhetorical analysis of justifications. The second section puts in relation the analysis results with theoretical frameworks and contributions. The candidate confronted with several frameworks: Actor-Network-Theory, Institutional work and Boundary Work, Institutional Logic. Chapters are focused on different issues: a historical reconstruction of CSR; a reflection about symbolic adoption of recurrent labels; two case studies of Italian networks, in order to confront institutional and boundary works; a theoretical model of institutional change based on contradiction and institutional complexity; the application of the model to CSR and Sustainability, proposing Sustainability as a possible institutional logic.

Spectral theory of differential operators on finite metric graphs and on bounded domains

Die vorliegende Arbeit widmet sich der Spektraltheorie von Differentialoperatoren auf metrischen Graphen und von indefiniten Differentialoperatoren auf beschränkten Gebieten. Sie besteht aus zwei Teilen. Im Ersten werden endliche, nicht notwendigerweise kompakte, metrische Graphen und die Hilberträume von quadratintegrierbaren Funktionen auf diesen betrachtet. Alle quasi-m-akkretiven Laplaceoperatoren auf solchen Graphen werden charakterisiert, und Abschätzungen an die negativen Eigenwerte selbstadjungierter Laplaceoperatoren werden hergeleitet. Weiterhin wird die Wohlgestelltheit eines gemischten Diffusions- und Transportproblems auf kompakten Graphen durch die Anwendung von Halbgruppenmethoden untersucht. Eine Verallgemeinerung des indefiniten Operators $-tfrac{d}{dx}sgn(x)tfrac{d}{dx}$ von Intervallen auf metrische Graphen wird eingeführt. Die Spektral- und Streutheorie der selbstadjungierten Realisierungen wird detailliert besprochen. Im zweiten Teil der Arbeit werden Operatoren untersucht, die mit indefiniten Formen der Art $langlegrad v, A(cdot)grad urangle$ mit $u,vin H_0^1(Omega)subset L^2(Omega)$ und $OmegasubsetR^d$ beschränkt, assoziiert sind. Das Eigenwertverhalten entspricht in Dimension $d=1$ einer verallgemeinerten Weylschen Asymptotik und für $dgeq 2$ werden Abschätzungen an die Eigenwerte bewiesen. Die Frage, wann indefinite Formmethoden für Dimensionen $dgeq 2$ anwendbar sind, bleibt offen und wird diskutiert.

COSMIC-LAB: Unexpected Results from High-resolution Spectra of AGB Stars in Globular Clusters

We have used high-resolution spectra, acquired with UVES@ESO-VLT, to determine the chemical abundances of different samples of AGB and RGB stars in 4 Galactic globular clusters, namely 47Tuc, NGC3201, M22 and M62. For almost all the analyzed AGB stars we found a clear discrepancy between the iron abundance measured from neutral lines and that obtained from single ionized lines, while this discrepancy is not obtained for the RGB samples observed in the same clusters and analyzed with the same procedure. Such a behavior exactly corresponds to what expected in the case of Non-Local Thermodynamical Equilibrium (NLTE) in the star atmosphere. These results have a huge impact on the proper determination of GC chemistry. In fact, one of the most intriguing consequences is that, at odds with previous claims, no iron spread is found in NGC3201 and M22 if the iron abundance is obtained from ionized lines only.

Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors

Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new 18F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed 18F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable 18F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for 18F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K⊂2.2.2]+/carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved.rnThe promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were conducted. The synthesis of the folate-boron clusters was straightforward. At first, a linker molecule based on maleic acid was synthesized, which was coupled to the boron cluster via Michael Addition of a thiol and alkene and subsequently coupled to the targeting moiety using CuAAC. The new conjugates of folate and boron clusters led to a significant increase of boron concentration in the cell of about 5-times compared to currently used and approved boron pharmaceuticals. rnMoreover, azido-folate derivatives were coupled to macromolecular carrier systems (pHPMA), which showed an enhanced and specific accumulation at target sites (up to 2.5-times) during in vivo experiments. A specific blockade could be observed up to 30% indicating an efficient targeting effect. A new kind of nanoparticles consisting of a PDLLA core and p((HPMA)-b-LMA)) as surfactants were developed and successfully radiolabeled via 18F-click chemistry in good RCYs of 8±3%rnThe nanoparticles were obtained via the miniemulsion technique in combination with solvent evaporation. The 18F-labeled nanoparticles were applied to in vivo testing using a mouse model. PET imaging showed a “mixed” biodistribution of low molecular weight as well as high molecular weight systems, indicating a partial loss of the 18F-labeled surfactant.rnIn conclusion, the presented work successfully utilized the FR-targeting concept in both, the diagnostic field (PET imaging) and for therapeutic approaches (BNCT, drug delivery systems). As a result, the high potential of FR-targeting in oncological applications has been shown and was confirmed by small animal PET imaging.rn

Wet and dry model granulates under mechanical load : a confocal microscopy study

Granular matter, also known as bulk solids, consists of discrete particles with sizes between micrometers and meters. They are present in many industrial applications as well as daily life, like in food processing, pharmaceutics or in the oil and mining industry. When handling granular matter the bulk solids are stored, mixed, conveyed or filtered. These techniques are based on observations in macroscopic experiments, i.e. rheological examinations of the bulk properties. Despite the amply investigations of bulk mechanics, the relation between single particle motion and macroscopic behavior is still not well understood. For exploring the microscopic properties on a single particle level, 3D imaging techniques are required.rnThe objective of this work was the investigation of single particle motions in a bulk system in 3D under an external mechanical load, i.e. compression and shear. During the mechanical load the structural and dynamical properties of these systems were examined with confocal microscopy. Therefor new granular model systems in the wet and dry state were designed and prepared. As the particles are solid bodies, their motion is described by six degrees of freedom. To explore their entire motion with all degrees of freedom, a technique to visualize the rotation of spherical micrometer sized particles in 3D was developed. rnOne of the foci during this dissertation was a model system for dry cohesive granular matter. In such systems the particle motion during a compression of the granular matter was investigated. In general the rotation of single particles was the more sensitive parameter compared to the translation. In regions with large structural changes the rotation had an earlier onset than the translation. In granular systems under shear, shear dilatation and shear zone formation were observed. Globally the granular sediments showed a shear behavior, which was known already from classical shear experiments, for example with Jenike cells. Locally the shear zone formation was enhanced, when near the applied load a pre-diluted region existed. In regions with constant volume fraction a mixing between the different particle layers occurred. In particular an exchange of particles between the current flowing region and the non-flowing region was observed. rnThe second focus was on model systems for wet granular matter, where an additional binding liquid is added to the particle suspension. To examine the 3D structure of the binding liquid on the micrometer scale independently from the particles, a second illumination and detection beam path was implemented. In shear and compression experiments of wet clusters and bulk systems completely different dynamics compared to dry cohesive models systems occured. In a Pickering emulsion-like system large structural changes predominantly occurred in the local environment of binding liquid droplets. These large local structural changes were due to an energy interplay between the energy stored in the binding droplet during its deformation and the binding energy of particles at the droplet interface. rnConfocal microscopy in combination with nanoindentation gave new insights into the single particle motions and dynamics of granular systems under a mechanical load. These novel experimental results can help to improve the understanding of the relationship between bulk properties of granular matter, such as volume fraction or yield stress and the dynamics on a single particle level.rnrn

Development of models and methods to simulate peptide-assisted nucleation and growth of calcium-minerals

In den vergangenen Jahren wurden einige bislang unbekannte Phänomene experimentell beobachtet, wie etwa die Existenz unterschiedlicher Prä-Nukleations-Strukturen. Diese haben zu einem neuen Verständnis von Prozessen, die auf molekularer Ebene während der Nukleation und dem Wachstum von Kristallen auftreten, beigetragen. Die Auswirkungen solcher Prä-Nukleations-Strukturen auf den Prozess der Biomineralisation sind noch nicht hinreichend verstanden. Die Mechanismen, mittels derer biomolekulare Modifikatoren, wie Peptide, mit Prä-Nukleations-Strukturen interagieren und somit den Nukleationsprozess von Mineralen beeinflussen könnten, sind vielfältig. Molekulare Simulationen sind zur Analyse der Formation von Prä-Nukleations-Strukturen in Anwesenheit von Modifikatoren gut geeignet. Die vorliegende Arbeit beschreibt einen Ansatz zur Analyse der Interaktion von Peptiden mit den in Lösung befindlichen Bestandteilen der entstehenden Kristalle mit Hilfe von Molekular-Dynamik Simulationen.rnUm informative Simulationen zu ermöglichen, wurde in einem ersten Schritt die Qualität bestehender Kraftfelder im Hinblick auf die Beschreibung von mit Calciumionen interagierenden Oligoglutamaten in wässrigen Lösungen untersucht. Es zeigte sich, dass große Unstimmigkeiten zwischen etablierten Kraftfeldern bestehen, und dass keines der untersuchten Kraftfelder eine realistische Beschreibung der Ionen-Paarung dieser komplexen Ionen widerspiegelte. Daher wurde eine Strategie zur Optimierung bestehender biomolekularer Kraftfelder in dieser Hinsicht entwickelt. Relativ geringe Veränderungen der auf die Ionen–Peptid van-der-Waals-Wechselwirkungen bezogenen Parameter reichten aus, um ein verlässliches Modell für das untersuchte System zu erzielen. rnDas umfassende Sampling des Phasenraumes der Systeme stellt aufgrund der zahlreichen Freiheitsgrade und der starken Interaktionen zwischen Calciumionen und Glutamat in Lösung eine besondere Herausforderung dar. Daher wurde die Methode der Biasing Potential Replica Exchange Molekular-Dynamik Simulationen im Hinblick auf das Sampling von Oligoglutamaten justiert und es erfolgte die Simulation von Peptiden verschiedener Kettenlängen in Anwesenheit von Calciumionen. Mit Hilfe der Sketch-Map Analyse konnten im Rahmen der Simulationen zahlreiche stabile Ionen-Peptid-Komplexe identifiziert werden, welche die Formation von Prä-Nukleations-Strukturen beeinflussen könnten. Abhängig von der Kettenlänge des Peptids weisen diese Komplexe charakteristische Abstände zwischen den Calciumionen auf. Diese ähneln einigen Abständen zwischen den Calciumionen in jenen Phasen von Calcium-Oxalat Kristallen, die in Anwesenheit von Oligoglutamaten gewachsen sind. Die Analogie der Abstände zwischen Calciumionen in gelösten Ionen-Peptid-Komplexen und in Calcium-Oxalat Kristallen könnte auf die Bedeutung von Ionen-Peptid-Komplexen im Prozess der Nukleation und des Wachstums von Biomineralen hindeuten und stellt einen möglichen Erklärungsansatz für die Fähigkeit von Oligoglutamaten zur Beeinflussung der Phase des sich formierenden Kristalls dar, die experimentell beobachtet wurde.

Axion-like particles and the 3.5 keV line in 4D string models

This work is focused on axions and axion like particles (ALPs) and their possible relation with the 3.55 keV photon line detected, in recent years, from galaxy clusters and other astrophysical objects. We focus on axions that come from string compactification and we study the vacuum structure of the resulting low energy 4D N=1 supergravity effective field theory. We then provide a model which might explain the 3.55 keV line through the following processes. A 7.1 keV dark matter axion decays in two light axions, which, in turn, are transformed into photons thanks to the Primakoff effect and the existence of a kinetic mixing between two U(1)s gauge symmetries belonging respectively to the hidden and the visible sector. We present two models, the first one gives an outcome inconsistent with experimental data, while the second can yield the desired result.

Surgical dislocation of the hip for a locked traumatic posterior dislocation with associated femoral neck and acetabular fractures

Traumatic posterior dislocation of the hip associated with a fracture of the posterior acetabular wall and of the neck of the femur is a rare injury. A 29-year-old man presented at a level 1 trauma centre with a locked posterior dislocation of the right hip, with fractures of the femoral neck and the posterior wall of the acetabulum after a bicycle accident. An attempted closed reduction had failed. This case report describes in detail the surgical management and the clinical and radiological outcome. Open reduction and fixation with preservation of the intact retinaculum was undertaken within five hours of injury with surgical dislocation of the hip and a trochanteric osteotomy. Two years after operation the function of the injured hip was good. Plain radiographs and MR scans showed early signs of osteoarthritis with some loss of joint space but no evidence of avascular necrosis. The patient had begun skiing and hiking again. The combination of fractures of the neck of the femur and of the posterior wall of the acetabulum hampers closed reduction of a posterior dislocation of the hip. Surgical dislocation of the hip with trochanteric flip osteotomy allows controlled open reduction of the fractures, with inspection of the hip joint and preservation of the vascular supply.

Reliability, construct and criterion validity of the KIDSCREEN-10 score: a short measure for children and adolescents' well-being and health-related quality of life

Background To assess the criterion and construct validity of the KIDSCREEN-10 well-being and health-related quality of life (HRQoL) score, a short version of the KIDSCREEN-52 and KIDSCREEN-27 instruments. Methods The child self-report and parent report versions of the KIDSCREEN-10 were tested in a sample of 22,830 European children and adolescents aged 8–18 and their parents (n = 16,237). Correlation with the KIDSCREEN-52 and associations with other generic HRQoL measures, physical and mental health, and socioeconomic status were examined. Score differences by age, gender, and country were investigated. Results Correlations between the 10-item KIDSCREEN score and KIDSCREEN-52 scales ranged from r = 0.24 to 0.72 (r = 0.27–0.72) for the self-report version (proxy-report version). Coefficients below r = 0.5 were observed for the KIDSCREEN-52 dimensions Financial Resources and Being Bullied only. Cronbach alpha was 0.82 (0.78), test–retest reliability was ICC = 0.70 (0.67) for the self- (proxy-)report version. Correlations between other children self-completed HRQoL questionnaires and KIDSCREEN-10 ranged from r = 0.43 to r = 0.63 for the KIDSCREEN children self-report and r = 0.22–0.40 for the KIDSCREEN parent proxy report. Known group differences in HRQoL between physically/mentally healthy and ill children were observed in the KIDSCREEN-10 self and proxy scores. Associations with self-reported psychosomatic complaints were r = −0.52 (−0.36) for the KIDSCREEN-10 self-report (proxy-report). Statistically significant differences in KIDSCREEN-10 self and proxy scores were found by socioeconomic status, age, and gender. Conclusions Our results indicate that the KIDSCREEN-10 provides a valid measure of a general HRQoL factor in children and adolescents, but the instrument does not represent well most of the single dimensions of the original KIDSCREEN-52. Test–retest reliability was slightly below a priori defined thresholds.

Multilocus sequence analysis and rpoB sequencing of Mycobacterium abscessus (sensu lato) strains

Mycobacterium abscessus, Mycobacterium bolletii, and Mycobacterium massiliense (Mycobacterium abscessus sensu lato) are closely related species that currently are identified by the sequencing of the rpoB gene. However, recent studies show that rpoB sequencing alone is insufficient to discriminate between these species, and some authors have questioned their current taxonomic classification. We studied here a large collection of M. abscessus (sensu lato) strains by partial rpoB sequencing (752 bp) and multilocus sequence analysis (MLSA). The final MLSA scheme developed was based on the partial sequences of eight housekeeping genes: argH, cya, glpK, gnd, murC, pgm, pta, and purH. The strains studied included the three type strains (M. abscessus CIP 104536(T), M. massiliense CIP 108297(T), and M. bolletii CIP 108541(T)) and 120 isolates recovered between 1997 and 2007 in France, Germany, Switzerland, and Brazil. The rpoB phylogenetic tree confirmed the existence of three main clusters, each comprising the type strain of one species. However, divergence values between the M. massiliense and M. bolletii clusters all were below 3% and between the M. abscessus and M. massiliense clusters were from 2.66 to 3.59%. The tree produced using the concatenated MLSA gene sequences (4,071 bp) also showed three main clusters, each comprising the type strain of one species. The M. abscessus cluster had a bootstrap value of 100% and was mostly compact. Bootstrap values for the M. massiliense and M. bolletii branches were much lower (71 and 61%, respectively), with the M. massiliense cluster having a fuzzy aspect. Mean (range) divergence values were 2.17% (1.13 to 2.58%) between the M. abscessus and M. massiliense clusters, 2.37% (1.5 to 2.85%) between the M. abscessus and M. bolletii clusters, and 2.28% (0.86 to 2.68%) between the M. massiliense and M. bolletii clusters. Adding the rpoB sequence to the MLSA-concatenated sequence (total sequence, 4,823 bp) had little effect on the clustering of strains. We found 10/120 (8.3%) isolates for which the concatenated MLSA gene sequence and rpoB sequence were discordant (e.g., M. massiliense MLSA sequence and M. abscessus rpoB sequence), suggesting the intergroup lateral transfers of rpoB. In conclusion, our study strongly supports the recent proposal that M. abscessus, M. massiliense, and M. bolletii should constitute a single species. Our findings also indicate that there has been a horizontal transfer of rpoB sequences between these subgroups, precluding the use of rpoB sequencing alone for the accurate identification of the two proposed M. abscessus subspecies.