Earthquake forecasting and seismic hazard analysis: some insights on the testing phase and the modeling

This thesis is divided in three chapters. In the first chapter we analyse the results of the world forecasting experiment run by the Collaboratory for the Study of Earthquake Predictability (CSEP). We take the opportunity of this experiment to contribute to the definition of a more robust and reliable statistical procedure to evaluate earthquake forecasting models. We first present the models and the target earthquakes to be forecast. Then we explain the consistency and comparison tests that are used in CSEP experiments to evaluate the performance of the models. Introducing a methodology to create ensemble forecasting models, we show that models, when properly combined, are almost always better performing that any single model. In the second chapter we discuss in depth one of the basic features of PSHA: the declustering of the seismicity rates. We first introduce the Cornell-McGuire method for PSHA and we present the different motivations that stand behind the need of declustering seismic catalogs. Using a theorem of the modern probability (Le Cam's theorem) we show that the declustering is not necessary to obtain a Poissonian behaviour of the exceedances that is usually considered fundamental to transform exceedance rates in exceedance probabilities in the PSHA framework. We present a method to correct PSHA for declustering, building a more realistic PSHA. In the last chapter we explore the methods that are commonly used to take into account the epistemic uncertainty in PSHA. The most widely used method is the logic tree that stands at the basis of the most advanced seismic hazard maps. We illustrate the probabilistic structure of the logic tree, and then we show that this structure is not adequate to describe the epistemic uncertainty. We then propose a new probabilistic framework based on the ensemble modelling that properly accounts for epistemic uncertainties in PSHA.

Synthesis and surface modification of silver and gold nanoparticles. Nanomedicine applications against Glioblastoma Multiforme.

In the last decades noble metal nanoparticles (NPs) arose as one of the most powerful tools for applications in nanomedicine field and cancer treatment. Glioblastoma multiforme (GBM), in particular, is one of the most aggressive malignant brain tumors that nowadays still presents a dramatic scenario concerning median survival. Gold nanorods (GNRs) and silver nanoparticles (AgNPs) could find applications such as diagnostic imaging, hyperthermia and glioblastoma therapy. During these three years, both GNRs and AgNPs were synthesized with the “salt reduction” method and, through a novel double phase transfer process, using specifically designed thiol-based ligands, lipophilic GNRs and AgNPs were obtained and separately entrapped into biocompatible and biodegradable PEG-based polymeric nanoparticles (PNPs) suitable for drug delivery within the body. Moreover, a synergistic effect of AgNPs with the Alisertib drug, were investigated thanks to the simultaneous entrapment of these two moieties into PNPs. In addition, Chlorotoxin (Cltx), a peptide that specifically recognize brain cancer cells, was conjugated onto the external surface of PNPs. The so-obtained novel nanosystems were evaluated for in vitro and in vivo applications against glioblastoma multiforme. In particular, for GNRs-PNPs, their safety, their suitability as optoacoustic contrast agents, their selective laser-induced cells death and finally, a high tumor retention were all demonstrated. Concerning AgNPs-PNPs, promising tumor toxicity and a strong synergistic effect with Alisertib was observed (IC50 10 nM), as well as good in vivo biodistribution, high tumor uptake and significative tumor reduction in tumor bearing mice. Finally, the two nanostructures were linked together, through an organic framework, exploiting the click chemistry azido-alkyne Huisgen cycloaddition, between two ligands previously attached to the NPs surface; this multifunctional complex nanosystem was successfully entrapped into PNPs with nanoparticles’ properties maintenance, obtaining in this way a powerful and promising tool for cancer fight and defeat.

Analysis and mathematical modeling of wave-structure interaction

The aim of this thesis, included within the THESEUS project, is the development of a mathematical model 2DV two-phase, based on the existing code IH-2VOF developed by the University of Cantabria, able to represent together the overtopping phenomenon and the sediment transport. Several numerical simulations were carried out in order to analyze the flow characteristics on a dike crest. The results show that the seaward/landward slope does not affect the evolution of the flow depth and velocity over the dike crest whereas the most important parameter is the relative submergence. Wave heights decrease and flow velocities increase while waves travel over the crest. In particular, by increasing the submergence, the wave height decay and the increase of the velocity are less marked. Besides, an appropriate curve able to fit the variation of the wave height/velocity over the dike crest were found. Both for the wave height and for the wave velocity different fitting coefficients were determined on the basis of the submergence and of the significant wave height. An equation describing the trend of the dimensionless coefficient c_h for the wave height was derived. These conclusions could be taken into consideration for the design criteria and the upgrade of the structures. In the second part of the thesis, new equations for the representation of the sediment transport in the IH-2VOF model were introduced in order to represent beach erosion while waves run-up and overtop the sea banks during storms. The new model allows to calculate sediment fluxes in the water column together with the sediment concentration. Moreover it is possible to model the bed profile evolution. Different tests were performed under low-intensity regular waves with an homogeneous layer of sand on the bottom of a channel in order to analyze the erosion-deposition patterns and verify the model results.

Formation and surface exchange of nitrous acid

Die salpetrige Säure (HONO) ist eine der reaktiven Stickstoffkomponenten der Atmosphäre und Pedosphäre. Die genauen Bildungswege von HONO, sowie der gegenseitige Austausch von HONO zwischen Atmosphäre und Pedosphäre sind noch nicht vollständig aufgedeckt. Bei der HONO-Photolyse entsteht das Hydroxylradikal (OH) und Stickstoffmonooxid (NO), was die Bedeutsamkeit von HONO für die atmosphärische Photochemie widerspiegelt.rnUm die genannte Bildung von HONO im Boden und dessen anschließenden Austausch mit der Atmosphäre zu untersuchen, wurden Messungen von Bodenproben mit dynamischen Kammern durchgeführt. Im Labor gemessene Emissionsflüsse von Wasser, NO und HONO zeigen, dass die Emission von HONO in vergleichbarem Umfang und im gleichen Bodenfeuchtebereich wie die für NO (von 6.5 bis 56.0 % WHC) stattfindet. Die Höhe der HONO-Emissionsflüsse bei neutralen bis basischen pH-Werten und die Aktivierungsenergie der HONO-Emissionsflüsse führen zu der Annahme, dass die mikrobielle Nitrifikation die Hauptquelle für die HONO-Emission darstellt. Inhibierungsexperimente mit einer Bodenprobe und die Messung einer Reinkultur von Nitrosomonas europaea bestärkten diese Theorie. Als Schlussfolgerung wurde das konzeptionelle Model der Bodenemission verschiedener Stickstoffkomponenten in Abhängigkeit von dem Wasserhaushalt des Bodens für HONO erweitert.rnIn einem weiteren Versuch wurde zum Spülen der dynamischen Kammer Luft mit erhöhtem Mischungsverhältnis von HONO verwendet. Die Messung einer hervorragend charakterisierten Bodenprobe zeigte bidirektionale Flüsse von HONO. Somit können Böden nicht nur als HONO-Quelle, sondern auch je nach Bedingungen als effektive Senke dienen. rnAußerdem konnte gezeigt werden, dass das Verhältnis von HONO- zu NO-Emissionen mit dem pH-Wert des Bodens korreliert. Grund könnte die erhöhte Reaktivität von HONO bei niedrigem pH-Wert und die längere Aufenthaltsdauer von HONO verursacht durch reduzierte Gasdiffusion im Bodenporenraum sein, da ein niedriger pH-Wert mit erhöhter Bodenfeuchte am Maximum der Emission einhergeht. Es konnte gezeigt werden, dass die effektive Diffusion von Gasen im Bodenporenraum und die effektive Diffusion von Ionen in der Bodenlösung die HONO-Produktion und den Austausch von HONO mit der Atmosphäre begrenzen. rnErgänzend zu den Messungen im Labor wurde HONO während der Messkampagne HUMPPA-COPEC 2010 im borealen Nadelwald simultan in der Höhe von 1 m über dem Boden und 2 bis 3 m über dem Blätterdach gemessen. Die Budgetberechnungen für HONO zeigen, dass für HONO sämtliche bekannte Quellen und Senken in Bezug auf die übermächtige HONO-Photolyserate tagsüber vernachlässigbar sind (< 20%). Weder Bodenemissionen von HONO, noch die Photolyse von an Oberflächen adsorbierter Salpetersäure können die fehlende Quelle erklären. Die lichtinduzierte Reduktion von Stickstoffdioxid (NO2) an Oberflächen konnte nicht ausgeschlossen werden. Es zeigte sich jedoch, dass die fehlende Quelle stärker mit der HONO-Photolyserate korreliert als mit der entsprechenden Photolysefrequenz, die proportional zur Photolysefrequenz von NO2 ist. Somit lässt sich schlussfolgern, dass entweder die Photolyserate von HONO überschätzt wird oder dass immer noch eine unbekannte, HONO-Quelle existiert, die mit der Photolyserate sehr stark korreliert. rn rn

The adsorption of biomolecules to multi-walled carbon nanotubes is influenced by both pulmonary surfactant lipids and surface chemistry

Background During production and processing of multi-walled carbon nanotubes (MWCNTs), they may be inhaled and may enter the pulmonary circulation. It is essential that interactions with involved body fluids like the pulmonary surfactant, the blood and others are investigated, particularly as these interactions could lead to coating of the tubes and may affect their chemical and physical characteristics. The aim of this study was to characterize the possible coatings of different functionalized MWCNTs in a cell free environment. Results To simulate the first contact in the lung, the tubes were coated with pulmonary surfactant and subsequently bound lipids were characterized. The further coating in the blood circulation was simulated by incubating the tubes in blood plasma. MWCNTs were amino (NH2)- and carboxyl (-COOH)-modified, in order to investigate the influence on the bound lipid and protein patterns. It was shown that surfactant lipids bind unspecifically to different functionalized MWCNTs, in contrast to the blood plasma proteins which showed characteristic binding patterns. Patterns of bound surfactant lipids were altered after a subsequent incubation in blood plasma. In addition, it was found that bound plasma protein patterns were altered when MWCNTs were previously coated with pulmonary surfactant. Conclusions A pulmonary surfactant coating and the functionalization of MWCNTs have both the potential to alter the MWCNTs blood plasma protein coating and to determine their properties and behaviour in biological systems.

Operator variability using different polishing methods and surface geometry of a nanohybrid composite

This study evaluated the operator variability of different finishing and polishing techniques. After placing 120 composite restorations (Tetric EvoCeram) in plexiglassmolds, the surface of the specimens was roughened in a standardized manner. Twelve operators with different experience levels polished the specimens using the following finishing/polishing procedures: method 1 (40 ?m diamond [40D], 15 ?m diamond [15D], 42 ?m silicon carbide polisher [42S], 6 ?m silicon carbide polisher [6S] and Occlubrush [O]); method 2 (40D, 42S, 6S and O); method 3 (40D, 42S, 6S and PoGo); method 4 (40D, 42S and PoGo) and method 5 (40D, 42S and O). The mean surface roughness (Ra) was measured with a profilometer. Differences between the methods were analyzed with non-parametric ANOVA and pairwise Wilcoxon signed rank tests (?=0.05). All the restorations were qualitatively assessed using SEM. Methods 3 and 4 showed the best polishing results and method 5 demonstrated the poorest. Method 5 was also most dependent on the skills of the operator. Except for method 5, all of the tested procedures reached a clinically acceptable surface polish of Ra?0.2 ?m. Polishing procedures can be simplified without increasing variability between operators and without jeopardizing polishing results.

Dimorphism in Shell Shape and Strength in Two Species of Emydid Turtle

This study investigates the mechanical implications of shell shape differences between males and females of two North American turtle species: Chrysemys picta and Glyptemys insculpta. These species show patterns of sexual dimorphism that are common to many species of turtle. Females have wider and more highly domed shells, whereas males tend to have flatter, more streamlined shells. In addition, the males of many terrestrial species have concave plastra, most likely to accommodate the domed shells of the females while mating. The purpose of this study was to determine whether the known morphological differences in male and female turtle shells are also associated with differences in shell strength. Landmark coordinate data were collected from the shells of males and females of both species. These data were used to create digital models of each shell for finite-element (FE) analysis. FE models were generated by transforming a single base model of a turtle shell to match the shapes of each specimen examined in this study. All models were assigned the same material properties and restraints. Twelve load cases, each representing a predator’s bite at a different location on the carapace, were applied separately to the models. Subsequently, Von Mises stresses were extracted for each element of each model. Overall, the shells of females of both species exhibited significantly lower maximum and average stresses for a given load than those of their male counterparts. Male G. insculpta exhibited significant increases in stresses because of the concave shape of their plastra. We suggest that the mechanical implications of shell shape differences between males and females may have a large impact on many aspects of the biology of these turtle species.

Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 μm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.

Combined bone and soft-tissue augmentation surgery in temporo-orbital contour reconstruction

Temporal hollowing due to temporal muscle atrophy after standard skull base surgery is common. Various techniques have been previously described to correct the disfiguring defect. Most often reconstruction is performed using freehand molded polymethylmethacrylate cement. This method and material are insufficient in terms of aesthetic results and implant characteristics. We herein propose reconstruction of such defects with a polyetheretherketone (PEEK)-based patient-specific implant (PSI) including soft-tissue augmentation to preserve normal facial topography. We describe a patient who presented with a large temporo-orbital hemangioma that had been repaired with polymethylmethacrylate 25 years earlier. Because of a toxic skin atrophy fistula, followed by infection and meningitis, this initial implant had to be removed. The large, disfiguring temporo-orbital defect was reconstructed with a PEEK-based PSI. The lateral orbital wall and the temporal muscle atrophy were augmented with computer-aided design and surface modeling techniques. The operative procedure to implant and adopt the reconstructed PEEK-based PSI was simple, and an excellent cosmetic outcome was achieved. The postoperative clinical course was uneventful over a 5-year follow-up period. Polyetheretherketone-based combined bony and soft contour remodeling is a feasible and effective method for cranioplasty including combined bone and soft-tissue reconstruction of temporo-orbital defects. Manual reconstruction of this cosmetically delicate area carries an exceptional risk of disfiguring results. Augmentation surgery in this anatomic location needs accurate PSIs to achieve satisfactory cosmetic results. The cosmetic outcome achieved in this case is superior compared with previously reported techniques.

Mutagenesis and computer modeling studies of a GPCR conserved residue W5.43(194) in ligand recognition and signal transduction for CB2 receptor

W5.43(194), a conserved tryptophan residue among G-protein coupled receptors (GPCRs) and cannabinoid receptors (CB), was examined in the present report for its significance in CB2 receptor ligand binding and adenylyl cyclase (AC) activity. Computer modeling postulates that this site in CB2 may be involved in the affinity of WIN55212-2 and SR144528 through aromatic contacts. In the present study, we reported that a CB2 receptor mutant, W5.43(194)Y, which had a tyrosine (Y) substitution for tryptophan (W), retained the binding affinity for CB agonist CP55940, but reduced binding affinity for CB2 agonist WIN55212-2 and inverse agonist SR144528 by 8-fold and 5-fold, respectively; the CB2 W5.43(194)F and W5.43(194)A mutations significantly affect the binding activities of CP55940, WIN55212-2 and SR144528. Furthermore, we found that agonist-mediated inhibition of the forskolin-induced cAMP production was dramatically diminished in the CB2 mutant W5.43(194)Y, whereas W5.43(194)F and W5.43(194)A mutants resulted in complete elimination of downstream signaling, suggesting that W5.43(194) was essential for the full activation of CB2. These results indicate that both aromatic interaction and hydrogen bonding are involved in ligand binding for the residue W5.43(194), and the mutations of this tryptophan site may affect the conformation of the ligand binding pocket and therefore control the active conformation of the wild type CB2 receptor. W5.43(194)Y/F/A mutations also displayed noticeable enhancement of the constitutive activation probably attributed to the receptor conformational changes resulted from the mutations.

Synthesis and Surface Modification of CdSe and CdS Quantum Dots Exhibiting High Quantum Yield

The thesis investigates the effect of surface treatment with various reducing and oxidizing agents on the quantum yield (QY) of CdSe and CdS quantum dots (QDs). The QDs, as synthesized by the organometallic method, contained defect sites on their surface that trapped photons and prevented their radiative recombination, therefore resulting in adecreased QY. To passivate these defect sites and enhance the QY, the QDs were treated with various reducing and oxidizing agents, including: sodium borohydride (NaBH4), calcium hydride (CaH2), hydrazine (N2H4), benzoyl peroxide (C14H10O4), and tert-butylhydroperoxide (C4H10O2). It was hypothesized that the reducing/oxidizing agents reduced the ligands on the QD surface, causing them to detach, thereby allowing oxygen from atmospheric air to bind to the exposed cadmium. This cadmium oxdide (CdO) layeraround the QD surface satisfied the defect sites and resulted in an increased QY. To correlate what effect the reducing and oxidizing agents were having on the optical properties of the QDs, we investigated these treatments on the following factors:chalcogenide (Se vs. S), ligand (oleylamine vs. OA), coordinating solvent (ODE vs.TOA), and dispersant solvent (chloroform vs. toluene) on the overall optical properties of the QDs. The QY of each sample was calculated before and after the various surface treatments from ultra-violet visible spectroscopy (UV-Vis) and fluorescence spectroscopy data to determine if the treatment was successful.From our results, we found that sodium borohydride was the most effective surface treatment, with 10 of the 12 treatments resulting in an increased QY. Hydrazine, on the other hand, was the least effective treatments, as it quenched the QD fluorescence in every case. From these observations, we hypothesize that the effectiveness of the QD surface treatments was dependent on reaction rate. More specifically, when the surface treatment reaction happened too quickly, we hypothesize that the QDs began to aggregate, resulting in a quenched fluorescence. Furthermore, we believe that the reactionrate is dependent on concentration of the reducing/oxidizing agents, solubility of the agents in each solvent, and reactivity of the agents with water. The quantum yield of the QDs can therefore be maximized by slowing the reaction rate of each surface treatment toa rate that allows for the proper passivation of defect sites.