Sulla progettazione in zona sismica di strutture dotate di dissipatori fluido-viscosi: proposta di una metodologia

CHAPTER 1:FLUID-VISCOUS DAMPERS In this chapter the fluid-viscous dampers are introduced. The first section is focused on the technical characteristics of these devices, their mechanical behavior and the latest evolution of the technology whose they are equipped. In the second section we report the definitions and the guide lines about the design of these devices included in some international codes. In the third section the results of some experimental tests carried out by some authors on the response of these devices to external forces are discussed. On this purpose we report some technical schedules that are usually enclosed to the devices now available on the international market. In the third section we show also some analytic models proposed by various authors, which are able to describe efficiently the physical behavior of the fluid-viscous dampers. In the last section we propose some cases of application of these devices on existing structures and on new-construction structures. We show also some cases in which these devices have been revealed good for aims that lies outside the reduction of seismic actions on the structures. CHAPTER 2:DESIGN METHODS PROPOSED IN LITERATURE In this chapter the more widespread design methods proposed in literature for structures equipped by fluid-viscous dampers are introduced. In the first part the response of sdf systems in the case of harmonic external force is studied, in the last part the response in the case of random external force is discussed. In the first section the equations of motion in the case of an elastic-linear sdf system equipped with a non-linear fluid-viscous damper undergoing a harmonic force are introduced. This differential problem is analytically quite complex and it’s not possible to be solved in a closed form. Therefore some authors have proposed approximate solution methods. The more widespread methods are based on equivalence principles between a non-linear device and an equivalent linear one. Operating in this way it is possible to define an equivalent damping ratio and the problem becomes linear; the solution of the equivalent problem is well-known. In the following section two techniques of linearization, proposed by some authors in literature, are described: the first technique is based on the equivalence of the energy dissipated by the two devices and the second one is based on the equivalence of power consumption. After that we compare these two techniques by studying the response of a sdf system undergoing a harmonic force. By introducing the equivalent damping ratio we can write the equation of motion of the non-linear differential problem in an implicit form, by dividing, as usual, for the mass of the system. In this way, we get a reduction of the number of variables, by introducing the natural frequency of the system. The equation of motion written in this form has two important properties: the response is linear dependent on the amplitude of the external force and the response is dependent on the ratio of the frequency of the external harmonic force and the natural frequency of the system only, and not on their single values. All these considerations, in the last section, are extended to the case of a random external force. CHAPTER 3: DESIGN METHOD PROPOSED In this chapter the theoretical basis of the design method proposed are introduced. The need to propose a new design method for structures equipped with fluid-viscous dampers arises from the observation that the methods reported in literature are always iterative, because the response affects some parameters included in the equation of motion (such as the equivalent damping ratio). In the first section the dimensionless parameterε is introduced. This parameter has been obtained from the definition of equivalent damping ratio. The implicit form of the equation of motion is written by introducing the parameter ε, instead of the equivalent damping ratio. This new implicit equation of motions has not any terms affected by the response, so that once ε is known the response can be evaluated directly. In the second section it is discussed how the parameter ε affects some characteristics of the response: drift, velocity and base shear. All the results described till this point have been obtained by keeping the non-linearity of the behavior of the dampers. In order to get a linear formulation of the problem, that is possible to solve by using the well-known methods of the dynamics of structures, as we did before for the iterative methods by introducing the equivalent damping ratio, it is shown how the equivalent damping ratio can be evaluated from knowing the value of ε. Operating in this way, once the parameter ε is known, it is quite easy to estimate the equivalent damping ratio and to proceed with a classic linear analysis. In the last section it is shown how the parameter ε could be taken as reference for the evaluation of the convenience of using non-linear dampers instead of linear ones on the basis of the type of external force and the characteristics of the system. CHAPTER 4: MULTI-DEGREE OF FREEDOM SYSTEMS In this chapter the design methods of a elastic-linear mdf system equipped with non-linear fluidviscous dampers are introduced. It has already been shown that, in the sdf systems, the response of the structure can be evaluated through the estimation of the equivalent damping ratio (ξsd) assuming the behavior of the structure elastic-linear. We would to mention that some adjusting coefficients, to be applied to the equivalent damping ratio in order to consider the actual behavior of the structure (that is non-linear), have already been proposed in literature; such coefficients are usually expressed in terms of ductility, but their treatment is over the aims of this thesis and we does not go into further. The method usually proposed in literature is based on energy equivalence: even though this procedure has solid theoretical basis, it must necessary include some iterative process, because the expression of the equivalent damping ratio contains a term of the response. This procedure has been introduced primarily by Ramirez, Constantinou et al. in 2000. This procedure is reported in the first section and it is defined “Iterative Method”. Following the guide lines about sdf systems reported in the previous chapters, it is introduced a procedure for the assessment of the parameter ε in the case of mdf systems. Operating in this way the evaluation of the equivalent damping ratio (ξsd) can be done directly without implementing iterative processes. This procedure is defined “Direct Method” and it is reported in the second section. In the third section the two methods are analyzed by studying 4 cases of two moment-resisting steel frames undergoing real accelerogramms: the response of the system calculated by using the two methods is compared with the numerical response obtained from the software called SAP2000-NL, CSI product. In the last section a procedure to create spectra of the equivalent damping ratio, affected by the parameter ε and the natural period of the system for a fixed value of exponent α, starting from the elasticresponse spectra provided by any international code, is introduced.

Normalized Frobenius condition number of the orthogonal projections of the identity

[EN]This paper deals with the orthogonal projection (in the Frobenius sense) AN of the identity matrix I onto the matrix subspace AS (A ? Rn×n, S being an arbitrary subspace of Rn×n). Lower and upper bounds on the normalized Frobenius condition number of matrix AN are given. Furthermore, for every matrix subspace S ? Rn×n, a new index bF (A, S), which generalizes the normalized Frobenius condition number of matrix A, is defined and analyzed...

A molecular dynamics study of the influence of chain branching on the properties of polymer systems

Die vorliegende Arbeit beschäftigt sich mit dem Einfluß von Kettenverzweigungen unterschiedlicher Topologien auf die statischen Eigenschaften von Polymeren. Diese Untersuchungen werden mit Hilfe von Monte-Carlo- und Molekular-Dynamik-Simulationen durchgeführt.Zunächst werden einige theoretische Konzepte und Modelle eingeführt, welche die Beschreibung von Polymerketten auf mesoskopischen Längenskalen gestatten. Es werden wichtige Bestimmungsgrößen eingeführt und erläutert, welche zur quantitativen Charakterisierung von Verzweigungsstrukturen bei Polymeren geeignet sind. Es wird ebenso auf die verwendeten Optimierungstechniken eingegangen, die bei der Implementierung des Computerprogrammes Verwendung fanden. Untersucht werden neben linearen Polymerketten unterschiedliche Topolgien -Sternpolymere mit variabler Armzahl, Übergang von Sternpolymeren zu linearen Polymeren, Ketten mit variabler Zahl von Seitenketten, reguläre Dendrimere und hyperverzweigte Strukturen - in Abhängigkeit von der Lösungsmittelqualität. Es wird zunächst eine gründliche Analyse des verwendeten Simulationsmodells an sehr langen linearen Einzelketten vorgenommen. Die Skalierungseigenschaften der linearen Ketten werden untersucht in dem gesamten Lösungsmittelbereich vom guten Lösungsmittel bis hin zu weitgehend kollabierten Ketten im schlechten Lösungsmittel. Ein wichtiges Ergebnis dieser Arbeit ist die Bestätigung der Korrekturen zum Skalenverhalten des hydrodynamischen Radius Rh. Dieses Ergebnis war möglich aufgrund der großen gewählten Kettenlängen und der hohen Qualität der erhaltenen Daten in dieser Arbeit, insbesondere bei den linearen ketten, und es steht im Widerspruch zu vielen bisherigen Simulations-Studien und experimentellen Arbeiten. Diese Korrekturen zum Skalenverhalten wurden nicht nur für die linearen Ketten, sondern auch für Sternpolymere mit unterchiedlicher Armzahl gezeigt. Für lineare Ketten wird der Einfluß von Polydispersität untersucht.Es wird gezeigt, daß eine eindeutige Abbildung von Längenskalen zwischen Simulationsmodell und Experiment nicht möglich ist, da die zu diesem Zweck verwendete dimensionslose Größe eine zu schwache Abhängigkeit von der Polymerisation der Ketten besitzt. Ein Vergleich von Simulationsdaten mit industriellem Low-Density-Polyäthylen(LDPE) zeigt, daß LDPE in Form von stark verzweigten Ketten vorliegt.Für reguläre Dendrimere konnte ein hochgradiges Zurückfalten der Arme in die innere Kernregion nachgewiesen werden.

Studio di Mutazioni Geniche e Variazioni Copy-Number implicate nel deficit combinato degli Ormoni Ipofisari(CPHD)

La crescita normale di un individuo è il risultato dell’azione coordinata di molteplici ormoni e recettori codificati da geni e a tal proposito, discreto interesse è stato dato ai geni tipici dell’asse del GH. Tuttavia altri geni, più a monte di questi e responsabili dello sviluppo dell’ipofisi contribuiscono alla crescita normale o patologica. Alcuni geni studiati sono POU1F1, PROP1, LHX3, LHX4, HESX1, SOX3 e svariate loro mutazioni sono state identificate come causa di panipopituarismo (CPHD=Combined Pituitary Hormone Deficiency). In realtà la ricerca genetica non spiega ancora molte anomalie ipofisarie e molte mutazioni devono ancora essere identificate. Uno degli scopi del dottorato, svoltosi nel laboratorio di Genetica molecolare di Pediatria, è stata l’identificazione di mutazioni geniche da un gruppo di pazienti CPHD considerando in particolare i geni POU1F1, LHX3, SOX3, non ancora messi a punto presso il laboratorio. L’approccio sperimentale si è basato sulle seguenti fasi: prelievo delle informazioni di sequenza da GeneBank, progettazione di primers per amplificare le porzioni esoniche, messa a punto delle fasi della PCR e del sequenziamento, analisi della sequenza e confronto con le informazioni di sequenza depositate allo scopo di rintracciare eventuali mutazioni o varianti. La bassa percentuale di mutazioni in questi geni non ha permesso finora di rintracciare mutazioni nelle porzioni esoniche salvo che in un soggetto, nell’esone 6 di LHX3b (nuova mutazione, recessiva eterozigote, c.1248A>G implicata nella mutazione p.T377A della sequenza proteica). Un metodo di screening di questa mutazione impiegando l’enzima di restrizione SacII è stato usato, senza rilevare nessun altra occorrenza dell’allele mutato in 53 soggetti di controllo. Oltre alla messa a punto del sequenziamento e di alcune tecniche di analisi di singoli SNP o piccoli INDELs per i 3 geni, la ricerca svolta è stata orientata all’impiego di metodi di rilevamento di riarrangiamenti genetici comportanti ampie delezioni e/o variazioni del copy-number di esoni/interi geni detto MLPA (Multiplex Ligation-dependent Probe Amplification) e progettato da MRC-Holland. Il sequenziamento infatti non permette di rilevare tali alterazioni quando sono ampie ed in eterozigosi. Per esempio, in un’ampia delezione in eterozigosi, l’intervallo delimitato dai primers usati per la PCR può non includere totalmente la porzione interessata da delezione su un cromosoma cosicché la PCR ed il sequnziamento si basano solo sulle informazioni dell’altro cromosoma non deleto. Un vantaggio della tecnica MLPA, è l’analisi contemporanea di una quarantina di siti posti su svariati geni. Questa metodo tuttavia può essere affetto da un certo margine di errore spesso dipendente dalla qualità del DNA e dovrebbe essere affiancato e validato da altre tecniche più impegnativa dal punto di vista sperimentale ma più solide, per esempio la Real Time PCR detta anche PCR quantitativa (qPCR). In laboratorio, grazie all’MLPA si è verificata la condizione di delezione eterozigote di un paziente “storico” per il gene GH1 e la stessa mutazione è stata rilevata anche con la qPCR usando lo strumento Corbett Rotor Gene 6000 (Explera). Invece un’analisi solo con la qPCR di variazioni del copy-number (CNV) per SOX3 in pazienti maschili non ha ancora evidenziato anomalie. Entrambe le tecniche hanno aspetti interessanti, il miglior approccio al momento sembra un’analisi iniziale di pazienti con l’MLPA, seguita dalla verifica di un eventuale esito anomalo impiegando la real-time PCR.

Cosmological perturbations in generalized theories of gravity

The first part of the thesis concerns the study of inflation in the context of a theory of gravity called "Induced Gravity" in which the gravitational coupling varies in time according to the dynamics of the very same scalar field (the "inflaton") driving inflation, while taking on the value measured today since the end of inflation. Through the analytical and numerical analysis of scalar and tensor cosmological perturbations we show that the model leads to consistent predictions for a broad variety of symmetry-breaking inflaton's potentials, once that a dimensionless parameter entering into the action is properly constrained. We also discuss the average expansion of the Universe after inflation (when the inflaton undergoes coherent oscillations about the minimum of its potential) and determine the effective equation of state. Finally, we analyze the resonant and perturbative decay of the inflaton during (p)reheating. The second part is devoted to the study of a proposal for a quantum theory of gravity dubbed "Horava-Lifshitz (HL) Gravity" which relies on power-counting renormalizability while explicitly breaking Lorentz invariance. We test a pair of variants of the theory ("projectable" and "non-projectable") on a cosmological background and with the inclusion of scalar field matter. By inspecting the quadratic action for the linear scalar cosmological perturbations we determine the actual number of propagating degrees of freedom and realize that the theory, being endowed with less symmetries than General Relativity, does admit an extra gravitational degree of freedom which is potentially unstable. More specifically, we conclude that in the case of projectable HL Gravity the extra mode is either a ghost or a tachyon, whereas in the case of non-projectable HL Gravity the extra mode can be made well-behaved for suitable choices of a pair of free dimensionless parameters and, moreover, turns out to decouple from the low-energy Physics.

Hot wire manufacturing and resolution effects in high Reynolds number flows

Lo studio della turbolenza è di fondamentale importanza non solo per la fluidodinamica teorica ma anche perchè viene riscontrata in una moltitudine di problemi di interesse ingegneristico. All'aumentare del numero di Reynolds, le scale caratteristiche tendono a ridurre le loro dimensioni assolute. Nella fluidodinamica sperimentale già da lungo tempo si è affermata l'anemometria a filo caldo, grazie ad ottime caratteristiche di risoluzione spaziale e temporale. Questa tecnica, caratterizzata da un basso costo e da una relativa semplicità, rende possibile la realizzazione di sensori di tipo artigianale, che hanno il vantaggio di poter essere relizzati in dimensioni inferiori. Nonostante l'ottima risoluzione spaziale degli hot-wire, infatti, si può verificare, ad alto numero di Reynolds, che le dimensioni dell'elemento sensibile siano superiori a quelle delle piccole scale. Questo impedisce al sensore di risolvere correttamente le strutture più piccole. Per questa tesi di laurea è stato allestito un laboratorio per la costruzione di sensori a filo caldo con filo di platino. Sono in questo modo stati realizzati diversi sensori dalle dimensioni caratteristiche inferiori a quelle dei sensori disponibili commercialmente. I sensori ottenuti sono quindi stati testati in un getto turbolento, dapprima confrontandone la risposta con un sensore di tipo commerciale, per verificarne il corretto funzionamento. In seguito si sono eseguite misure più specifiche e limitate ad alcune particolari zone all'interno del campo di moto, dove è probabile riscontrare effetti di risoluzione spaziale. Sono stati analizzati gli effetti della dimensione fisica del sensore sui momenti statistici centrali, sugli spettri di velocità e sulle funzioni di densità di probabilità.

The Euler number of OGradys 10-dimensional symplectic manifold

Wir berechnen die Eulerzahl der 10-dimensionalen exzeptionellen irreduziblen symplektischen Mannigfaltigkeit, die von O Grady konstruiert wurde. Die Idee besteht darin, zunächst eine Lagrangefaserung zu konstruieren und dann die Eulerzahlen der Fasern zu berechnen. Es stellt sich heraus, dass fast alle Fasern die Eulerzahl 0 haben, und deswegen reduziert sich das Problem auf die Berechnung der Eulerzahlen der übrigen Fasern. Diese Fasern sind Modulräume von halbstabilen Garben auf singulären Kurven. Der Hauptteil dieser Dissertation ist der Berechnung der Eulerzahlen dieser Modulräume gewidmet. Diese Resultate sind von unabhängigem Interesse.

Analisi di “Copy Number Variants” ed identificazione di nuovi geni candidati per l’Autismo e Ritardo Mentale

I disturbi dello spettro autistico (DSA) ed il ritardo mentale (RM) sono caratterizzati da un’eziologia genetica complessa ed eterogenea. Grazie ai recenti sviluppi nella ricerca genomica, è stato possibile dimostrare il ruolo di numerose copy number variants (CNVs) nella patogenesi di questi disturbi, anche se nella maggior parte dei casi l’eziologia rimane ancora sconosciuta. Questo lavoro riguarda l’identificazione e la caratterizzazione dei CNVs in famiglie con DSA e RM. E’ stata studiata una microdelezione in 7q31 che coinvolge i geni IMMP2L e DOCK4, trasmessa dalla madre con dislessia a due figli con autismo ed una figlia con dislessia. Nella stessa famiglia segrega una seconda microdelezione in 2q14 che inattiva il gene CNTNAP5 ed è trasmessa dal padre (con tratti autistici) ai due figli con autismo. Abbiamo quindi ipotizzato che i geni DOCK4 e CNTNAP5 potessero essere implicati, rispettivamente, nella suscettibilità a dislessia e DSA. Lo screening di numerosi individui affetti ha supportato la nostra ipotesi, con l’identificazione di una nuova microdelezione di DOCK4 che segrega con la dislessia, e 3 nuove varianti missenso in CNTNAP5 in individui con autismo. Dall’analisi genomica comparativa su array (aCGH) di individui con RM, è stata identificata una delezione nella regione 7q31.32, che coinvolge il gene CADPS2, in due fratelli con RM e tratti autistici, probabilmente ereditata dalla madre. Lo screening di mutazione di questo gene in individui con autismo o RM, ha portato all’identificazione di 3 varianti non sinonime, assenti nei controlli, ed ereditate per via materna. Poiché CADPS2 risiede in una regione genomica che contiene loci soggetti ad imprinting, abbiamo ipotizzato che il gene CADPS2 possa essere anch’esso caratterizzato da imprinting, con espressione monoallelica materna. Lo studio di espressione di CADPS2 in cellule del sangue ha avvalorato questa ipotesi, implicando perciò CADPS2 come un nuovo gene di suscettibilità per il RM e DSA.

Investigating the role of Copy Number Variants in Specific Language Impairment and identification of new candidate genes

Specific language impairment (SLI) is a complex neurodevelopmental disorder defined as an unexpected failure to develop normal language abilities for no obvious reason. Copy number variants (CNVs) are an important source of variation in the susceptibility to neuropsychiatric disorders. Therefore, a CNV study within SLI families was performed to investigate the role of structural variants in SLI. Among the identified CNVs, we focused on CNVs on chromosome 15q11-q13, recurrently observed in neuropsychiatric conditions, and a homozygous exonic microdeletion in ZNF277. Since this microdeletion falls within the AUTS1 locus, a region linked to autism spectrum disorders (ASD), we investigated a potential role of ZNF277 in SLI and ASD. Frequency data and expression analysis of the ZNF277 microdeletion suggested that this variant may contribute to the risk of language impairments in a complex manner, that is independent of the autism risk previously described in this region. Moreover, we identified an affected individual with a dihydropyrimidine dehydrogenase (DPD) deficiency, caused by compound heterozygosity of two deleterious variants in the gene DPYD. Since DPYD represents a good candidate gene for both SLI and ASD, we investigated its involvement in the susceptibility to these two disorders, focusing on the splicing variant rs3918290, the most common mutation in the DPD deficiency. We observed a higher frequency of rs3918290 in SLI cases (1.2%), compared to controls (~0.6%), while no difference was observed in a large ASD cohort. DPYD mutation screening in 4 SLI and 7 ASD families carrying the splicing variant identified six known missense changes and a novel variant in the promoter region. These data suggest that the combined effect of the mutations identified in affected individuals may lead to an altered DPD activity and that rare variants in DPYD might contribute to a minority of cases, in conjunction with other genetic or non-genetic factors.

Arrangiamenti di sfere: stime sul "kissing number".

La tesi ha lo scopo di iniziare, in quanto non lo esaurisce completamente, a riordinare il percorso fatto nella stima del kissing number.

Analysis of Copy Number Variants identifies new candidate genes for Autism Spectrum Disorder and Intellectual Disability

Autism spectrum disorder (ASD) and Intellectual Disability (ID) are complex neuropsychiatric disorders characterized by extensive clinical and genetic heterogeneity and with overlapping risk factors. The aim of my project was to further investigate the role of Copy Numbers Variants (CNVs), identified through genome-wide studies performed by the Autism Geome Project (AGP) and the CHERISH consortium in large cohorts of ASD and ID cases, respectively. Specifically, I focused on four rare genic CNVs, selected on the basis of their impact on interesting ASD/ID candidate genes: a) a compound heterozygous deletion involving CTNNA3, predicted to cause the lack of functional protein; b) a 15q13.3 duplication containing CHRNA7; c) a 2q31.1 microdeletion encompassing KLHL23, SSB and METTL5; d) Lastly, I investigated the putative imprinting regulation of the CADPS2 gene, disrupted by a maternal deletion in two siblings with ASD and ID. This study provides further evidence for the role of CTNNA3, CHRNA7, KLHL23 and CADPS2 as ASD and/or ID susceptibility genes, and highlights that rare genetic variation contributes to disease risk in different ways: some rare mutations, such as those impacting CTNNA3, act in a recessive mode of inheritance, while other CNVs, such as those occurring in the 15q13.3 region, are implicated in multiple developmental and/or neurological disorders possibly interacting with other susceptibility variants elsewhere in the genome. On the other hand, the discovery of a tissue-specific monoallelic expression for the CADPS2 gene, implicates the involvement of epigenetic regulatory mechanisms as risk factors conferring susceptibility to ASD/ID.

Volatile organic compounds at the air-sea interface : gas exchange rates, oceanic emissions and the effect of ocean acidification

Oceans are key sources and sinks in the global budgets of significant atmospheric trace gases, termed Volatile Organic Compounds (VOCs). Despite their low concentrations, these species have an important role in the atmosphere, influencing ozone photochemistry and aerosol physics. Surprisingly, little work has been done on assessing their emissions or transport mechanisms and rates between ocean and atmosphere, all of which are important when modelling the atmosphere accurately.rnA new Needle Trap Device (NTD) - GC-MS method was developed for the effective sampling and analysis of VOCs in seawater. Good repeatability (RSDs <16 %), linearity (R2 = 0.96 - 0.99) and limits of detection in the range of pM were obtained for DMS, isoprene, benzene, toluene, p-xylene, (+)-α-pinene and (-)-α-pinene. Laboratory evaluation and subsequent field application indicated that the proposed method can be used successfully in place of the more usually applied extraction techniques (P&T, SPME) to extend the suite of species typically measured in the ocean and improve detection limits. rnDuring a mesocosm CO2 enrichment study, DMS, isoprene and α-pinene were identified and quantified in seawater samples, using the above mentioned method. Based on correlations with available biological datasets, the effects of ocean acidification as well as possible ocean biological sources were investigated for all examined compounds. Future ocean's acidity was shown to decrease oceanic DMS production, possibly impact isoprene emissions but not affect the production of α-pinene. rnIn a separate activity, ocean - atmosphere interactions were simulated in a large scale wind-wave canal facility, in order to investigate the gas exchange process and its controlling mechanisms. Air-water exchange rates of 14 chemical species (of which 11 VOCs) spanning a wide range of solubility (dimensionless solubility, α = 0:4 to 5470) and diffusivity (Schmidt number in water, Scw = 594 to 1194) were obtained under various turbulent (wind speed at ten meters height, u10 = 0:8 to 15ms-1) and surfactant modulated (two different sized Triton X-100 layers) surface conditions. Reliable and reproducible total gas transfer velocities were obtained and the derived values and trends were comparable to previous investigations. Through this study, a much better and more comprehensive understanding of the gas exchange process was accomplished. The role of friction velocity, uw* and mean square slope, σs2 in defining phenomena such as waves and wave breaking, near surface turbulence, bubbles and surface films was recognized as very significant. uw* was determined as the ideal turbulent parameter while σs2 described best the related surface conditions. A combination of both uw* and σs2 variables, was found to reproduce faithfully the air-water gas exchange process. rnA Total Transfer Velocity (TTV) model provided by a compilation of 14 tracers and a combination of both uw* and σs2 parameters, is proposed for the first time. Through the proposed TTV parameterization, a new physical perspective is presented which provides an accurate TTV for any tracer within the examined solubility range. rnThe development of such a comprehensive air-sea gas exchange parameterization represents a highly useful tool for regional and global models, providing accurate total transfer velocity estimations for any tracer and any sea-surface status, simplifying the calculation process and eliminating inevitable calculation uncertainty connected with the selection or combination of different parameterizations.rnrn

The effect of diffusion gradient direction number on tractography of corticospinal tract in human brain: an along-tract analysis

Nel presente lavoro di tesi ho sviluppato un metodo di analisi di dati di DW-MRI (Diffusion-Weighted Magnetic Resonance Imaging)cerebrale, tramite un algoritmo di trattografia, per la ricostruzione del tratto corticospinale, in un campione di 25 volontari sani. Il diffusion tensor imaging (DTI) sfrutta la capacità del tensore di diffusione D di misurare il processo di diffusione dell’acqua, per stimare quantitativamente l’anisotropia dei tessuti. In particolare, nella sostanza bianca cerebrale la diffusione delle molecole di acqua è direzionata preferenzialmente lungo le fibre, mentre è ostacolata perpendicolarmente ad esse. La trattografia utilizza le informazioni ottenute tramite il DW imaging per fornire una misura della connettività strutturale fra diverse regioni del cervello. Nel lavoro si è concentrata l’attenzione sul fascio corticospinale, che è coinvolto nella motricità volontaria, trasmettendo gli impulsi dalla corteccia motoria ai motoneuroni del midollo spinale. Il lavoro si è articolato in 3 fasi. Nella prima ho sviluppato il pre-processing di immagini DW acquisite con un gradiente di diffusione sia 25 che a 64 direzioni in ognuno dei 25 volontari sani. Si è messo a punto un metodo originale ed innovativo, basato su “Regions of Interest” (ROIs), ottenute attraverso la segmentazione automatizzata della sostanza grigia e ROIs definite manualmente su un template comune a tutti i soggetti in esame. Per ricostruire il fascio si è usato un algoritmo di trattografia probabilistica che stima la direzione più probabile delle fibre e, con un numero elevato di direzioni del gradiente, riesce ad individuare, se presente, più di una direzione dominante (seconda fibra). Nella seconda parte del lavoro, ciascun fascio è stato suddiviso in 100 segmenti (percentili). Sono stati stimati anisotropia frazionaria (FA), diffusività media, probabilità di connettività, volume del fascio e della seconda fibra con un’analisi quantitativa “along-tract”, per ottenere un confronto accurato dei rispettivi percentili dei fasci nei diversi soggetti. Nella terza parte dello studio è stato fatto il confronto dei dati ottenuti a 25 e 64 direzioni del gradiente ed il confronto del fascio fra entrambi i lati. Dall’analisi statistica dei dati inter-subject e intra-subject è emersa un’elevata variabilità tra soggetti, dimostrando l’importanza di parametrizzare il tratto. I risultati ottenuti confermano che il metodo di analisi trattografica del fascio cortico-spinale messo a punto è risultato affidabile e riproducibile. Inoltre, è risultato che un’acquisizione con 25 direzioni di DTI, meglio tollerata dal paziente per la minore durata dello scan, assicura risultati attendibili. La principale applicazione clinica riguarda patologie neurodegenerative con sintomi motori sia acquisite, quali sindromi parkinsoniane sia su base genetica o la valutazione di masse endocraniche, per la definizione del grado di contiguità del fascio. Infine, sono state poste le basi per la standardizzazione dell’analisi quantitativa di altri fasci di interesse in ambito clinico o di studi di ricerca fisiopatogenetica.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.