Performance evaluation of asphalt pavements using the Incremental-Recursive procedure of the Mechanistic-Empirical design software CalME

Il concetto di “sostenibilità” si riferisce allo sviluppo dei sistemi umani attraverso il più piccolo impatto possibile sul sistema ambientale. Le opere che si inseriscono bene nel contesto ambientale circostante e le pratiche che rispettano le risorse in maniera tale da permettere una crescita e uno sviluppo a lungo termine senza impattare sull’ambiente sono indispensabili in una società moderna. I progressi passati, presenti e futuri che hanno reso i conglomerati bituminosi materiali sostenibili dal punto di vista ambientale sono particolarmente importanti data la grande quantità di conglomerato usato annualmente in Europa e negli Stati Uniti. I produttori di bitume e di conglomerato bituminoso stanno sviluppando tecniche innovative per ridurre l’impatto ambientale senza compromettere le prestazioni meccaniche finali. Un conglomerato bituminoso ad “alta lavorabilità” (WMA), pur sviluppando le stesse caratteristiche meccaniche, richiede un temperatura di produzione minore rispetto a quella di un tradizionale conglomerato bituminoso a caldo (HMA). L’abbassamento della temperature di produzione riduce le emissioni nocive. Questo migliora le condizioni dei lavoratori ed è orientato verso uno sviluppo sostenibile. L’obbiettivo principale di questa tesi di laurea è quello di dimostrare il duplice valore sia dal punto di vista dell’eco-compatibilità sia dal punto di vista meccanico di questi conglomerati bituminosi ad “alta lavorabilità”. In particolare in questa tesi di laurea è stato studiato uno SMA ad “alta lavorabilità” (PGGWMA). L’uso di materiali a basso impatto ambientale è la prima fase verso un progetto ecocompatibile ma non può che essere il punto di partenza. L’approccio ecocompatibile deve essere esteso anche ai metodi di progetto e alla caratterizzazione di laboratorio dei materiali perché solo in questo modo è possibile ricavare le massime potenzialità dai materiali usati. Un’appropriata caratterizzazione del conglomerato bituminoso è fondamentale e necessaria per una realistica previsione delle performance di una pavimentazione stradale. La caratterizzazione volumetrica (Mix Design) e meccanica (Deformazioni Permanenti e Comportamento a fatica) di un conglomerato bituminoso è una fase importante. Inoltre, al fine di utilizzare correttamente i materiali, un metodo di progetto avanzato ed efficiente, come quello rappresentato da un approccio Empirico-Meccanicistico (ME), deve essere utilizzato. Una procedura di progetto Empirico-Meccanicistica consiste di un modello strutturale capace di prevedere gli stati di tensione e deformazione all’interno della pavimentazione sotto l’azione del traffico e in funzione delle condizioni atmosferiche e di modelli empirici, calibrati sul comportamento dei materiali, che collegano la risposta strutturale alle performance della pavimentazione. Nel 1996 in California, per poter effettivamente sfruttare i benefici dei continui progressi nel campo delle pavimentazioni stradali, fu iniziato un estensivo progetto di ricerca mirato allo sviluppo dei metodi di progetto Empirico - Meccanicistici per le pavimentazioni stradali. Il risultato finale fu la prima versione del software CalME che fornisce all’utente tre approcci diversi di l’analisi e progetto: un approccio Empirico, uno Empirico - Meccanicistico classico e un approccio Empirico - Meccanicistico Incrementale - Ricorsivo. Questo tesi di laurea si concentra sulla procedura Incrementale - Ricorsiva del software CalME, basata su modelli di danno per quanto riguarda la fatica e l’accumulo di deformazioni di taglio dai quali dipendono rispettivamente la fessurazione superficiale e le deformazioni permanenti nella pavimentazione. Tale procedura funziona per incrementi temporali successivi e, usando i risultati di ogni incremento temporale, ricorsivamente, come input dell’incremento temporale successivo, prevede le condizioni di una pavimentazione stradale per quanto riguarda il modulo complesso dei diversi strati, le fessurazioni superficiali dovute alla fatica, le deformazioni permanenti e la rugosità superficiale. Al fine di verificare le propreità meccaniche del PGGWMA e le reciproche relazioni in termini di danno a fatica e deformazioni permanenti tra strato superficiale e struttura della pavimentazione per fissate condizioni ambientali e di traffico, è stata usata la procedura Incrementale – Ricorsiva del software CalME. Il conglomerato bituminoso studiato (PGGWMA) è stato usato in una pavimentazione stradale come strato superficiale di 60 mm di spessore. Le performance della pavimentazione sono state confrontate a quelle della stessa pavimentazione in cui altri tipi di conglomerato bituminoso sono stati usati come strato superficiale. I tre tipi di conglomerato bituminoso usati come termini di paragone sono stati: un conglomerato bituminoso ad “alta lavorabilità” con granulometria “chiusa” non modificato (DGWMA), un conglomerato bituminoso modificato con polverino di gomma con granulometria “aperta” (GGRAC) e un conglomerato bituminoso non modificato con granulometria “chiusa” (DGAC). Nel Capitolo I è stato introdotto il problema del progetto ecocompatibile delle pavimentazioni stradali. I materiali a basso impatto ambientale come i conglomerati bituminosi ad “alta lavorabilità” e i conglomerati bituminosi modificati con polverino di gomma sono stati descritti in dettaglio. Inoltre è stata discussa l’importanza della caratterizzazione di laboratorio dei materiali e il valore di un metodo razionale di progetto delle pavimentazioni stradali. Nel Capitolo II sono stati descritti i diversi approcci progettuali utilizzabili con il CalME e in particolare è stata spiegata la procedura Incrementale – Ricorsiva. Nel Capitolo III sono state studiate le proprietà volumetriche e meccaniche del PGGWMA. Test di Fatica e di Deformazioni Permanenti, eseguiti rispettivamente con la macchina a fatica per flessione su quattro punti e il Simple Shear Test device (macchina di taglio semplice), sono stati effettuati su provini di conglomerato bituminoso e i risultati dei test sono stati riassunti. Attraverso questi dati di laboratorio, i parametri dei modelli della Master Curve, del danno a fatica e dell’accumulo di deformazioni di taglio usati nella procedura Incrementale – Ricorsiva del CalME sono stati valutati. Infine, nel Capitolo IV, sono stati presentati i risultati delle simulazioni di pavimentazioni stradali con diversi strati superficiali. Per ogni pavimentazione sono stati analizzati la fessurazione superficiale complessiva, le deformazioni permanenti complessive, il danno a fatica e la profondità delle deformazioni in ognuno degli stati legati.

Transcriptional functions of DNA Topoisomerases at a genome-wide scale and a single gene levels

The DNA topology is an important modifier of DNA functions. Torsional stress is generated when right handed DNA is either over- or underwound, producing structural deformations which drive or are driven by processes such as replication, transcription, recombination and repair. DNA topoisomerases are molecular machines that regulate the topological state of the DNA in the cell. These enzymes accomplish this task by either passing one strand of the DNA through a break in the opposing strand or by passing a region of the duplex from the same or a different molecule through a double-stranded cut generated in the DNA. Because of their ability to cut one or two strands of DNA they are also target for some of the most successful anticancer drugs used in standard combination therapies of human cancers. An effective anticancer drug is Camptothecin (CPT) that specifically targets DNA topoisomerase 1 (TOP 1). The research project of the present thesis has been focused on the role of human TOP 1 during transcription and on the transcriptional consequences associated with TOP 1 inhibition by CPT in human cell lines. Previous findings demonstrate that TOP 1 inhibition by CPT perturbs RNA polymerase (RNAP II) density at promoters and along transcribed genes suggesting an involvement of TOP 1 in RNAP II promoter proximal pausing site. Within the transcription cycle, promoter pausing is a fundamental step the importance of which has been well established as a means of coupling elongation to RNA maturation. By measuring nascent RNA transcripts bound to chromatin, we demonstrated that TOP 1 inhibition by CPT can enhance RNAP II escape from promoter proximal pausing site of the human Hypoxia Inducible Factor 1 (HIF-1) and c-MYC genes in a dose dependent manner. This effect is dependent from Cdk7/Cdk9 activities since it can be reversed by the kinases inhibitor DRB. Since CPT affects RNAP II by promoting the hyperphosphorylation of its Rpb1 subunit the findings suggest that TOP 1inhibition by CPT may increase the activity of Cdks which in turn phosphorylate the Rpb1 subunit of RNAP II enhancing its escape from pausing. Interestingly, the transcriptional consequences of CPT induced topological stress are wider than expected. CPT increased co-transcriptional splicing of exon1 and 2 and markedly affected alternative splicing at exon 11. Surprisingly despite its well-established transcription inhibitory activity, CPT can trigger the production of a novel long RNA (5’aHIF-1) antisense to the human HIF-1 mRNA and a known antisense RNA at the 3’ end of the gene, while decreasing mRNA levels. The effects require TOP 1 and are independent from CPT induced DNA damage. Thus, when the supercoiling imbalance promoted by CPT occurs at promoter, it may trigger deregulation of the RNAP II pausing, increased chromatin accessibility and activation/derepression of antisense transcripts in a Cdks dependent manner. A changed balance of antisense transcripts and mRNAs may regulate the activity of HIF-1 and contribute to the control of tumor progression After focusing our TOP 1 investigations at a single gene level, we have extended the study to the whole genome by developing the “Topo-Seq” approach which generates a map of genome-wide distribution of sites of TOP 1 activity sites in human cells. The preliminary data revealed that TOP 1 preferentially localizes at intragenic regions and in particular at 5’ and 3’ ends of genes. Surprisingly upon TOP 1 downregulation, which impairs protein expression by 80%, TOP 1 molecules are mostly localized around 3’ ends of genes, thus suggesting that its activity is essential at these regions and can be compensate at 5’ ends. The developed procedure is a pioneer tool for the detection of TOP 1 cleavage sites across the genome and can open the way to further investigations of the enzyme roles in different nuclear processes.

Neural basis of visual deficits recovery: visual residual functions and multisensory integration.

The ability of integrating into a unified percept sensory inputs deriving from different sensory modalities, but related to the same external event, is called multisensory integration and might represent an efficient mechanism of sensory compensation when a sensory modality is damaged by a cortical lesion. This hypothesis has been discussed in the present dissertation. Experiment 1 explored the role of superior colliculus (SC) in multisensory integration, testing patients with collicular lesions, patients with subcortical lesions not involving the SC and healthy control subjects in a multisensory task. The results revealed that patients with collicular lesions, paralleling the evidence of animal studies, demonstrated a loss of multisensory enhancement, in contrast with control subjects, providing the first lesional evidence in humans of the essential role of SC in mediating audio-visual integration. Experiment 2 investigated the role of cortex in mediating multisensory integrative effects, inducing virtual lesions by inhibitory theta-burst stimulation on temporo-parietal cortex, occipital cortex and posterior parietal cortex, demonstrating that only temporo-parietal cortex was causally involved in modulating the integration of audio-visual stimuli at the same spatial location. Given the involvement of the retino-colliculo-extrastriate pathway in mediating audio-visual integration, the functional sparing of this circuit in hemianopic patients is extremely relevant in the perspective of a multisensory-based approach to the recovery of unisensory defects. Experiment 3 demonstrated the spared functional activity of this circuit in a group of hemianopic patients, revealing the presence of implicit recognition of the fearful content of unseen visual stimuli (i.e. affective blindsight), an ability mediated by the retino-colliculo-extrastriate pathway and its connections with amygdala. Finally, Experiment 4 provided evidence that a systematic audio-visual stimulation is effective in inducing long-lasting clinical improvements in patients with visual field defect and revealed that the activity of the spared retino-colliculo-extrastriate pathway is responsible of the observed clinical amelioration, as suggested by the greater improvement observed in patients with cortical lesions limited to the occipital cortex, compared to patients with lesions extending to other cortical areas, found in tasks high demanding in terms of spatial orienting. Overall, the present results indicated that multisensory integration is mediated by the retino-colliculo-extrastriate pathway and that a systematic audio-visual stimulation, activating this spared neural circuit, is able to affect orientation towards the blind field in hemianopic patients and, therefore, might constitute an effective and innovative approach for the rehabilitation of unisensory visual impairments.

Simulation studies of correlation functions and relaxation in polymeric systems

We investigate the statics and dynamics of a glassy,non-entangled, short bead-spring polymer melt with moleculardynamics simulations. Temperature ranges from slightlyabove the mode-coupling critical temperature to the liquidregime where features of a glassy liquid are absent. Ouraim is to work out the polymer specific effects on therelaxation and particle correlation. We find the intra-chain static structure unaffected bytemperature, it depends only on the distance of monomersalong the backbone. In contrast, the distinct inter-chainstructure shows pronounced site-dependence effects at thelength-scales of the chain and the nearest neighbordistance. There, we also find the strongest temperaturedependence which drives the glass transition. Both the siteaveraged coupling of the monomer and center of mass (CM) andthe CM-CM coupling are weak and presumably not responsiblefor a peak in the coherent relaxation time at the chain'slength scale. Chains rather emerge as soft, easilyinterpenetrating objects. Three particle correlations arewell reproduced by the convolution approximation with theexception of model dependent deviations. In the spatially heterogeneous dynamics of our system weidentify highly mobile monomers which tend to follow eachother in one-dimensional paths forming ``strings''. Thesestrings have an exponential length distribution and aregenerally short compared to the chain length. Thus, arelaxation mechanism in which neighboring mobile monomersmove along the backbone of the chain seems unlikely.However, the correlation of bonded neighbors is enhanced. When liquids are confined between two surfaces in relativesliding motion kinetic friction is observed. We study ageneric model setup by molecular dynamics simulations for awide range of sliding speeds, temperatures, loads, andlubricant coverings for simple and molecular fluids. Instabilities in the particle trajectories are identified asthe origin of kinetic friction. They lead to high particlevelocities of fluid atoms which are gradually dissipatedresulting in a friction force. In commensurate systemsfluid atoms follow continuous trajectories for sub-monolayercoverings and consequently, friction vanishes at low slidingspeeds. For incommensurate systems the velocity probabilitydistribution exhibits approximately exponential tails. Weconnect this velocity distribution to the kinetic frictionforce which reaches a constant value at low sliding speeds. This approach agrees well with the friction obtaineddirectly from simulations and explains Amontons' law on themicroscopic level. Molecular bonds in commensurate systemslead to incommensurate behavior, but do not change thequalitative behavior of incommensurate systems. However,crossed chains form stable load bearing asperities whichstrongly increase friction.

The massless two-loop two-point function and zeta functions in counterterms of Feynman diagrams

The main part of this thesis describes a method of calculating the massless two-loop two-point function which allows expanding the integral up to an arbitrary order in the dimensional regularization parameter epsilon by rewriting it as a double Mellin-Barnes integral. Closing the contour and collecting the residues then transforms this integral into a form that enables us to utilize S. Weinzierl's computer library nestedsums. We could show that multiple zeta values and rational numbers are sufficient for expanding the massless two-loop two-point function to all orders in epsilon. We then use the Hopf algebra of Feynman diagrams and its antipode, to investigate the appearance of Riemann's zeta function in counterterms of Feynman diagrams in massless Yukawa theory and massless QED. The class of Feynman diagrams we consider consists of graphs built from primitive one-loop diagrams and the non-planar vertex correction, where the vertex corrections only depend on one external momentum. We showed the absence of powers of pi in the counterterms of the non-planar vertex correction and diagrams built by shuffling it with the one-loop vertex correction. We also found the invariance of some coefficients of zeta functions under a change of momentum flow through these vertex corrections.

Reinforcement Lernen mit Regularisierungsnetzwerken

Die Arbeit behandelt das Problem der Skalierbarkeit von Reinforcement Lernen auf hochdimensionale und komplexe Aufgabenstellungen. Unter Reinforcement Lernen versteht man dabei eine auf approximativem Dynamischen Programmieren basierende Klasse von Lernverfahren, die speziell Anwendung in der Künstlichen Intelligenz findet und zur autonomen Steuerung simulierter Agenten oder realer Hardwareroboter in dynamischen und unwägbaren Umwelten genutzt werden kann. Dazu wird mittels Regression aus Stichproben eine Funktion bestimmt, die die Lösung einer "Optimalitätsgleichung" (Bellman) ist und aus der sich näherungsweise optimale Entscheidungen ableiten lassen. Eine große Hürde stellt dabei die Dimensionalität des Zustandsraums dar, die häufig hoch und daher traditionellen gitterbasierten Approximationsverfahren wenig zugänglich ist. Das Ziel dieser Arbeit ist es, Reinforcement Lernen durch nichtparametrisierte Funktionsapproximation (genauer, Regularisierungsnetze) auf -- im Prinzip beliebig -- hochdimensionale Probleme anwendbar zu machen. Regularisierungsnetze sind eine Verallgemeinerung von gewöhnlichen Basisfunktionsnetzen, die die gesuchte Lösung durch die Daten parametrisieren, wodurch die explizite Wahl von Knoten/Basisfunktionen entfällt und so bei hochdimensionalen Eingaben der "Fluch der Dimension" umgangen werden kann. Gleichzeitig sind Regularisierungsnetze aber auch lineare Approximatoren, die technisch einfach handhabbar sind und für die die bestehenden Konvergenzaussagen von Reinforcement Lernen Gültigkeit behalten (anders als etwa bei Feed-Forward Neuronalen Netzen). Allen diesen theoretischen Vorteilen gegenüber steht allerdings ein sehr praktisches Problem: der Rechenaufwand bei der Verwendung von Regularisierungsnetzen skaliert von Natur aus wie O(n**3), wobei n die Anzahl der Daten ist. Das ist besonders deswegen problematisch, weil bei Reinforcement Lernen der Lernprozeß online erfolgt -- die Stichproben werden von einem Agenten/Roboter erzeugt, während er mit der Umwelt interagiert. Anpassungen an der Lösung müssen daher sofort und mit wenig Rechenaufwand vorgenommen werden. Der Beitrag dieser Arbeit gliedert sich daher in zwei Teile: Im ersten Teil der Arbeit formulieren wir für Regularisierungsnetze einen effizienten Lernalgorithmus zum Lösen allgemeiner Regressionsaufgaben, der speziell auf die Anforderungen von Online-Lernen zugeschnitten ist. Unser Ansatz basiert auf der Vorgehensweise von Recursive Least-Squares, kann aber mit konstantem Zeitaufwand nicht nur neue Daten sondern auch neue Basisfunktionen in das bestehende Modell einfügen. Ermöglicht wird das durch die "Subset of Regressors" Approximation, wodurch der Kern durch eine stark reduzierte Auswahl von Trainingsdaten approximiert wird, und einer gierigen Auswahlwahlprozedur, die diese Basiselemente direkt aus dem Datenstrom zur Laufzeit selektiert. Im zweiten Teil übertragen wir diesen Algorithmus auf approximative Politik-Evaluation mittels Least-Squares basiertem Temporal-Difference Lernen, und integrieren diesen Baustein in ein Gesamtsystem zum autonomen Lernen von optimalem Verhalten. Insgesamt entwickeln wir ein in hohem Maße dateneffizientes Verfahren, das insbesondere für Lernprobleme aus der Robotik mit kontinuierlichen und hochdimensionalen Zustandsräumen sowie stochastischen Zustandsübergängen geeignet ist. Dabei sind wir nicht auf ein Modell der Umwelt angewiesen, arbeiten weitestgehend unabhängig von der Dimension des Zustandsraums, erzielen Konvergenz bereits mit relativ wenigen Agent-Umwelt Interaktionen, und können dank des effizienten Online-Algorithmus auch im Kontext zeitkritischer Echtzeitanwendungen operieren. Wir demonstrieren die Leistungsfähigkeit unseres Ansatzes anhand von zwei realistischen und komplexen Anwendungsbeispielen: dem Problem RoboCup-Keepaway, sowie der Steuerung eines (simulierten) Oktopus-Tentakels.

Longitudinal evolution of cognitive functions in patients with multiple system atrophy: a prospective study

Introduction and Background: Multiple system atrophy (MSA) is a sporadic, adult-onset, progressive neurodegenerative disease characterized clinically by parkinsonism, cerebellar ataxia, and autonomic failure. We investigated cognitive functions longitudinally in a group of probable MSA patients, matching data with sleep parameters. Patients and Methods: 10 patients (7m/3f) underwent a detailed interview, a general and neurological examination, laboratory exams, MRI scans, a cardiovascular reflexes study, a battery of neuropsychological tests, and video-polysomnographic recording (VPSG). Patients were revaluated (T1) a mean of 16±5 (range: 12-28) months after the initial evaluation (T0). At T1, the neuropsychological assessment and VPSG were repeated. Results: The mean patient age was 57.8±6.4 years (range: 47-64) with a mean age at disease onset of 53.2±7.1 years (range: 43-61) and symptoms duration at T0 of 60±48 months (range: 12-144). At T0, 7 patients showed no cognitive deficits while 3 patients showed isolated cognitive deficits. At T1, 1 patient worsened developing multiple cognitive deficits from a normal condition. At T0 and T1, sleep efficiency was reduced, REM latency increased, NREM sleep stages 1-2 slightly increased. Comparisons between T1 and T0 showed a significant worsening in two tests of attention and no significant differences of VPSG parameters. No correlation was found between neuropsychological results and VPSG findings or RBD duration. Discussion and Conclusions: The majority of our patients do not show any cognitive deficits at T0 and T1, while isolated cognitive deficits are present in the remaining patients. Attention is the cognitive function which significantly worsened. Our data confirm the previous findings concerning the prevalence, type and the evolution of cognitive deficits in MSA. Regarding the developing of a condition of dementia, our data did not show a clear-cut diagnosis of dementia. We confirm a mild alteration of sleep structure. RBD duration does not correlate with neuropsychological findings.

Natural compounds Camptothecin and Triptolide: highly specific enzyme inhibitors and tools to dissect transcriptional functions

With this work I elucidated new and unexpected mechanisms of two strong and highly specific transcription inhibitors: Triptolide and Campthotecin. Triptolide (TPL) is a diterpene epoxide derived from the Chinese plant Trypterigium Wilfoordii Hook F. TPL inhibits the ATPase activity of XPB, a subunit of the general transcription factor TFIIH. In this thesis I found that degradation of Rbp1 (the largest subunit of RNA Polymerase II) caused by TPL treatments, is preceded by an hyperphosphorylation event at serine 5 of the carboxy-terminal domain (CTD) of Rbp1. This event is concomitant with a block of RNA Polymerase II at promoters of active genes. The enzyme responsible for Ser5 hyperphosphorylation event is CDK7. Notably, CDK7 downregulation rescued both Ser5 hyperphosphorylation and Rbp1 degradation triggered by TPL. Camptothecin (CPT), derived from the plant Camptotheca acuminata, specifically inhibits topoisomerase 1 (Top1). We first found that CPT induced antisense transcription at divergent CpG islands promoter. Interestingly, by immunofluorescence experiments, CPT was found to induce a burst of R loop structures (DNA/RNA hybrids) at nucleoli and mitochondria. We then decided to investigate the role of Top1 in R loop homeostasis through a short interfering RNA approach (RNAi). Using DNA/RNA immunoprecipitation techniques coupled to NGS I found that Top1 depletion induces an increase of R loops at a genome-wide level. We found that such increase occurs on the entire gene body. At a subset of loci R loops resulted particularly stressed after Top1 depletion: some of these genes showed the formation of new R loops structures, whereas other loci showed a reduction of R loops. Interestingly we found that new peaks usually appear at tandem or divergent genes in the entire gene body, while losses of R loop peaks seems to be a feature specific of 3’ end regions of convergent genes.

Zeta and L-functions of elliptic curves

In questa tesi si studiano alcune proprietà fondamentali delle funzioni Zeta e L associate ad una curva ellittica. In particolare, si dimostra la razionalità della funzione Zeta e l'ipotesi di Riemann per due famiglie specifiche di curve ellittiche. Si studia poi il problema dell'esistenza di un prolungamento analitico al piano complesso della funzione L di una curva ellittica con moltiplicazione complessa, attraverso l'analisi diretta di due casi particolari.

3D-ultrastructure, functions and stress responses of rhogocytes from the freshwater gastropods Biomphalaria glabrata and Lymnaea stagnalis

Rhogocytes, also termed ‘pore cells’, exist free in the hemolymph or embedded in the connective tissue of different body parts of molluscs, notably gastropods. These unique cells can be round, elongated or irregularly shaped, and up to 30 μm in diameter. Their hallmark is the so-called slit apparatus: i.e. pocket-like invaginations of the plasma membrane creating extracellular lacunae, bridged by cytoplasmic bars. These bars form distinctive slits of ca. 20 nm width. A slit diaphragm composed of proteins establishes a molecular sieve with holes of 20 x 20 nm. Different functions have been assigned to this special molluscan cell type, notably biosynthesis of the hemolymph respiratory protein hemocyanin. It has further been proposed, but not proven, that in the case of red-blooded snail species rhogocytes might synthesize the hemoglobin. However, the secretion pathway of these hemolymph proteins, and the functional role of the enigmatic slit apparatus remained unclear. Additionally proposed functions of rhogocytes, such as heavy metal detoxification or hemolymph protein degradation, are also not well studied. This work provides more detailed electron microscopical, histological and immunobiochemical information on the structure and function of rhogocytes of the freshwater snails Biomphalaria glabrata and Lymnaea stagnalis. By in situ hybridization on mantle tissues, it proves that B. glabrata rhogocytes synthesize hemoglobin and L. stagnalis rhogocytes synthesize hemocyanin. Hemocyanin is present, in endoplasmic reticulum lacunae and in vesicles, as individual molecules or pseudo-crystalline arrays. The first 3D reconstructions of rhogocytes are provided by means of electron tomography and show unprecedented details of the slit apparatus. A highly dense material in the cytoplasmic bars close to the diaphragmatic slits was shown, by immunogold labeling, to contain actin. By immunofluorescence microscopy, the protein nephrin was localized at the periphery of rhogocytes. The presence of both proteins in the slit apparatus supports the previous hypothesis, hitherto solely based on similarities of the ultrastructure, that the molluscan rhogocytes are phylogenetically related to mammalian podocytes and insect nephrocytes. A possible secretion pathway of respiratory proteins that includes a transfer mechanism of vesicles through the diaphragmatic slits is proposed and discussed. We also studied, by electron microscopy, the reaction of rhogocytes in situ to two forms of animal stress: deprivation of food and cadmium contamination of the tank water. Significant cellular reactions to both stressors were observed and documented. Notably, the slit apparatus surface and the number of electron-dense cytoplasmic vesicles increased in response to cadmium stress. Food deprivation led to an increase in hemocyanin production. These observations are also discussed in the framework of using such animals as potential environmental biomarkers.

Hadronic correlation functions with quark-disconnected contributions in lattice QCD

One of the fundamental interactions in the Standard Model of particle physicsrnis the strong force, which can be formulated as a non-abelian gauge theoryrncalled Quantum Chromodynamics (QCD). rnIn the low-energy regime, where the QCD coupling becomes strong and quarksrnand gluons are confined to hadrons, a perturbativernexpansion in the coupling constant is not possible.rnHowever, the introduction of a four-dimensional Euclidean space-timernlattice allows for an textit{ab initio} treatment of QCD and provides arnpowerful tool to study the low-energy dynamics of hadrons.rnSome hadronic matrix elements of interest receive contributionsrnfrom diagrams including quark-disconnected loops, i.e. disconnected quarkrnlines from one lattice point back to the same point. The calculation of suchrnquark loops is computationally very demanding, because it requires knowledge ofrnthe all-to-all propagator. In this thesis we use stochastic sources and arnhopping parameter expansion to estimate such propagators.rnWe apply this technique to study two problems which relay crucially on therncalculation of quark-disconnected diagrams, namely the scalar form factor ofrnthe pion and the hadronic vacuum polarization contribution to the anomalousrnmagnet moment of the muon.rnThe scalar form factor of the pion describes the coupling of a charged pion torna scalar particle. We calculate the connected and the disconnected contributionrnto the scalar form factor for three different momentum transfers. The scalarrnradius of the pion is extracted from the momentum dependence of the form factor.rnThe use ofrnseveral different pion masses and lattice spacings allows for an extrapolationrnto the physical point. The chiral extrapolation is done using chiralrnperturbation theory ($chi$PT). We find that our pion mass dependence of thernscalar radius is consistent with $chi$PT at next-to-leading order.rnAdditionally, we are able to extract the low energy constant $ell_4$ from thernextrapolation, and ourrnresult is in agreement with results from other lattice determinations.rnFurthermore, our result for the scalar pion radius at the physical point isrnconsistent with a value that was extracted from $pipi$-scattering data. rnThe hadronic vacuum polarization (HVP) is the leading-order hadronicrncontribution to the anomalous magnetic moment $a_mu$ of the muon. The HVP canrnbe estimated from the correlation of two vector currents in the time-momentumrnrepresentation. We explicitly calculate the corresponding disconnectedrncontribution to the vector correlator. We find that the disconnectedrncontribution is consistent with zero within its statistical errors. This resultrncan be converted into an upper limit for the maximum contribution of therndisconnected diagram to $a_mu$ by using the expected time-dependence of therncorrelator and comparing it to the corresponding connected contribution. Wernfind the disconnected contribution to be smaller than $approx5%$ of thernconnected one. This value can be used as an estimate for a systematic errorrnthat arises from neglecting the disconnected contribution.rn

Applications of elliptic functions to solve differential equations

In questa tesi si mostrano alcune applicazioni degli integrali ellittici nella meccanica Hamiltoniana, allo scopo di risolvere i sistemi integrabili. Vengono descritte le funzioni ellittiche, in particolare la funzione ellittica di Weierstrass, ed elenchiamo i tipi di integrali ellittici costruendoli dalle funzioni di Weierstrass. Dopo aver considerato le basi della meccanica Hamiltoniana ed il teorema di Arnold Liouville, studiamo un esempio preso dal libro di Moser-Integrable Hamiltonian Systems and Spectral Theory, dove si prendono in considerazione i sistemi integrabili lungo la geodetica di un'ellissoide, e il sistema di Von Neumann. In particolare vediamo che nel caso n=2 abbiamo un integrale ellittico.

Lateralization of cognitive functions after stroke in childhood

A child's brain shows a remarkable ability to recover from adverse events such as stroke. Language functions recover particularly well, while visuo-spatial skills are more affected by brain damage, regardless of its localization. This study investigated the lateralization of language and visual search after childhood stroke.