Two fluid numerical model for coastal applications

Wave breaking is an important coastal process, influencing hydro-morphodynamic processes such as turbulence generation and wave energy dissipation, run-up on the beach and overtopping of coastal defence structures. During breaking, waves are complex mixtures of air and water (“white water”) whose properties affect velocity and pressure fields in the vicinity of the free surface and, depending on the breaker characteristics, different mechanisms for air entrainment are usually observed. Several laboratory experiments have been performed to investigate the role of air bubbles in the wave breaking process (Chanson & Cummings, 1994, among others) and in wave loading on vertical wall (Oumeraci et al., 2001; Peregrine et al., 2006, among others), showing that the air phase is not negligible since the turbulent energy dissipation involves air-water mixture. The recent advancement of numerical models has given valuable insights in the knowledge of wave transformation and interaction with coastal structures. Among these models, some solve the RANS equations coupled with a free-surface tracking algorithm and describe velocity, pressure, turbulence and vorticity fields (Lara et al. 2006 a-b, Clementi et al., 2007). The single-phase numerical model, in which the constitutive equations are solved only for the liquid phase, neglects effects induced by air movement and trapped air bubbles in water. Numerical approximations at the free surface may induce errors in predicting breaking point and wave height and moreover, entrapped air bubbles and water splash in air are not properly represented. The aim of the present thesis is to develop a new two-phase model called COBRAS2 (stands for Cornell Breaking waves And Structures 2 phases), that is the enhancement of the single-phase code COBRAS0, originally developed at Cornell University (Lin & Liu, 1998). In the first part of the work, both fluids are considered as incompressible, while the second part will treat air compressibility modelling. The mathematical formulation and the numerical resolution of the governing equations of COBRAS2 are derived and some model-experiment comparisons are shown. In particular, validation tests are performed in order to prove model stability and accuracy. The simulation of the rising of a large air bubble in an otherwise quiescent water pool reveals the model capability to reproduce the process physics in a realistic way. Analytical solutions for stationary and internal waves are compared with corresponding numerical results, in order to test processes involving wide range of density difference. Waves induced by dam-break in different scenarios (on dry and wet beds, as well as on a ramp) are studied, focusing on the role of air as the medium in which the water wave propagates and on the numerical representation of bubble dynamics. Simulations of solitary and regular waves, characterized by both spilling and plunging breakers, are analyzed with comparisons with experimental data and other numerical model in order to investigate air influence on wave breaking mechanisms and underline model capability and accuracy. Finally, modelling of air compressibility is included in the new developed model and is validated, revealing an accurate reproduction of processes. Some preliminary tests on wave impact on vertical walls are performed: since air flow modelling allows to have a more realistic reproduction of breaking wave propagation, the dependence of wave breaker shapes and aeration characteristics on impact pressure values is studied and, on the basis of a qualitative comparison with experimental observations, the numerical simulations achieve good results.

Characterization and modeling of the barrier properties in nanostructured systems

The object of the present study is the process of gas transport in nano-sized materials, i.e. systems having structural elements of the order of nanometers. The aim of this work is to advance the understanding of the gas transport mechanism in such materials, for which traditional models are not often suitable, by providing a correct interpretation of the relationship between diffusive phenomena and structural features. This result would allow the development new materials with permeation properties tailored on the specific application, especially in packaging systems. The methods used to achieve this goal were a detailed experimental characterization and different simulation methods. The experimental campaign regarded the determination of oxygen permeability and diffusivity in different sets of organic-inorganic hybrid coatings prepared via sol-gel technique. The polymeric samples coated with these hybrid layers experienced a remarkable enhancement of the barrier properties, which was explained by the strong interconnection at the nano-scale between the organic moiety and silica domains. An analogous characterization was performed on microfibrillated cellulose films, which presented remarkable barrier effect toward oxygen when it is dry, while in the presence of water the performance significantly drops. The very low value of water diffusivity at low activities is also an interesting characteristic which deals with its structural properties. Two different approaches of simulation were then considered: the diffusion of oxygen through polymer-layered silicates was modeled on a continuum scale with a CFD software, while the properties of n-alkanthiolate self assembled monolayers on gold were analyzed from a molecular point of view by means of a molecular dynamics algorithm. Modeling transport properties in layered nanocomposites, resulting from the ordered dispersion of impermeable flakes in a 2-D matrix, allowed the calculation of the enhancement of barrier effect in relation with platelets structural parameters leading to derive a new expression. On this basis, randomly distributed systems were simulated and the results were analyzed to evaluate the different contributions to the overall effect. The study of more realistic three-dimensional geometries revealed a prefect correspondence with the 2-D approximation. A completely different approach was applied to simulate the effect of temperature on the oxygen transport through self assembled monolayers; the structural information obtained from equilibrium MD simulations showed that raising the temperature, makes the monolayer less ordered and consequently less crystalline. This disorder produces a decrease in the barrier free energy and it lowers the overall resistance to oxygen diffusion, making the monolayer more permeable to small molecules.

Enhanced Mixed Integer Programming Techniques and Routing Problems

Mixed integer programming is up today one of the most widely used techniques for dealing with hard optimization problems. On the one side, many practical optimization problems arising from real-world applications (such as, e.g., scheduling, project planning, transportation, telecommunications, economics and finance, timetabling, etc) can be easily and effectively formulated as Mixed Integer linear Programs (MIPs). On the other hand, 50 and more years of intensive research has dramatically improved on the capability of the current generation of MIP solvers to tackle hard problems in practice. However, many questions are still open and not fully understood, and the mixed integer programming community is still more than active in trying to answer some of these questions. As a consequence, a huge number of papers are continuously developed and new intriguing questions arise every year. When dealing with MIPs, we have to distinguish between two different scenarios. The first one happens when we are asked to handle a general MIP and we cannot assume any special structure for the given problem. In this case, a Linear Programming (LP) relaxation and some integrality requirements are all we have for tackling the problem, and we are ``forced" to use some general purpose techniques. The second one happens when mixed integer programming is used to address a somehow structured problem. In this context, polyhedral analysis and other theoretical and practical considerations are typically exploited to devise some special purpose techniques. This thesis tries to give some insights in both the above mentioned situations. The first part of the work is focused on general purpose cutting planes, which are probably the key ingredient behind the success of the current generation of MIP solvers. Chapter 1 presents a quick overview of the main ingredients of a branch-and-cut algorithm, while Chapter 2 recalls some results from the literature in the context of disjunctive cuts and their connections with Gomory mixed integer cuts. Chapter 3 presents a theoretical and computational investigation of disjunctive cuts. In particular, we analyze the connections between different normalization conditions (i.e., conditions to truncate the cone associated with disjunctive cutting planes) and other crucial aspects as cut rank, cut density and cut strength. We give a theoretical characterization of weak rays of the disjunctive cone that lead to dominated cuts, and propose a practical method to possibly strengthen those cuts arising from such weak extremal solution. Further, we point out how redundant constraints can affect the quality of the generated disjunctive cuts, and discuss possible ways to cope with them. Finally, Chapter 4 presents some preliminary ideas in the context of multiple-row cuts. Very recently, a series of papers have brought the attention to the possibility of generating cuts using more than one row of the simplex tableau at a time. Several interesting theoretical results have been presented in this direction, often revisiting and recalling other important results discovered more than 40 years ago. However, is not clear at all how these results can be exploited in practice. As stated, the chapter is a still work-in-progress and simply presents a possible way for generating two-row cuts from the simplex tableau arising from lattice-free triangles and some preliminary computational results. The second part of the thesis is instead focused on the heuristic and exact exploitation of integer programming techniques for hard combinatorial optimization problems in the context of routing applications. Chapters 5 and 6 present an integer linear programming local search algorithm for Vehicle Routing Problems (VRPs). The overall procedure follows a general destroy-and-repair paradigm (i.e., the current solution is first randomly destroyed and then repaired in the attempt of finding a new improved solution) where a class of exponential neighborhoods are iteratively explored by heuristically solving an integer programming formulation through a general purpose MIP solver. Chapters 7 and 8 deal with exact branch-and-cut methods. Chapter 7 presents an extended formulation for the Traveling Salesman Problem with Time Windows (TSPTW), a generalization of the well known TSP where each node must be visited within a given time window. The polyhedral approaches proposed for this problem in the literature typically follow the one which has been proven to be extremely effective in the classical TSP context. Here we present an overall (quite) general idea which is based on a relaxed discretization of time windows. Such an idea leads to a stronger formulation and to stronger valid inequalities which are then separated within the classical branch-and-cut framework. Finally, Chapter 8 addresses the branch-and-cut in the context of Generalized Minimum Spanning Tree Problems (GMSTPs) (i.e., a class of NP-hard generalizations of the classical minimum spanning tree problem). In this chapter, we show how some basic ideas (and, in particular, the usage of general purpose cutting planes) can be useful to improve on branch-and-cut methods proposed in the literature.

Il Nilotinib nella terapia di prima linea della leucemia mieloide cronica

Background: Nilotinib is a potent and selective BCR-ABL inhibitor. The phase 3 ENESTnd trial demonstrated superior efficacy nilotinib vs imatinib, with higher and faster molecular responses. After 24 months, the rates of progression to accelerated-blastic phase (ABP) were 0.7% and 1.1% with nilotinib 300mg and 400mg BID, respectively, significantly lower compared to imatinib (4.2%). Nilotinib has been approved for the frontline treatment of Ph+ CML. With imatinib 400mg (IRIS trial), the rate of any event and of progression to ABP were higher during the first 3 years. Consequently, a confirmation of the durability of responses to nilotinib beyond 3 years is extremely important. Aims: To evaluate the response and the outcome of patients treated for 3 years with nilotinib 400mg BID as frontline therapy. Methods: A multicentre phase 2 trial was conducted by the GIMEMA CML WP (ClinicalTrials.gov.NCT00481052). Minimum 36-month follow-up data for all patients will be presented. Definitions: Major Molecular Response (MMR): BCR-ABL/ABL ratio <0,1%IS; Complete Molecular Response (CMR): undetectable transcript levels with ≥10,000 ABL transcripts; failures: according to the revised ELN recommendations; events: failures and treatment discontinuation for any reason. All the analysis has been made according to the intention-to-treat principle. Results: 73 patients enrolled: median age 51 years; 45% low, 41% intermediate and 14% high Sokal risk. The cumulative incidence of CCgR at 12 months was 100%. CCgR at each milestone: 78%, 96%, 96%, 95%, 92% at 3, 6, 12, 18 and 24 months, respectively. The overall estimated probability of MMR was 97%, while the rates of MMR at 3, 6, 12, 18 and 24 months were 52%, 66%, 85%, 81% and 82%, respectively. The overall estimated probability of CMR was 79%, while the rates of CMR at 12 and 24 months were 12% and 27%, respectively. No patient achieving a MMR progressed to AP. Only one patient progressed at 6 months to ABP and subsequently died (high Sokal risk, T315I mutation). Adverse events were mostly grade 1 or 2 and manageable with appropriate dose adaptations. During the first 12 months, the mean daily dose was 600-800mg in 74% of patients. The nilotinib last daily dose was as follows: 800mg in 46 (63%) patients, 600mg in 3 (4%) patients and 400mg in 18 (25%), 6 permanent discontinuations. Detail of discontinuation: 1 patient progressed to ABP; 3 patients had recurrent episodes of amylase and/or lipase increase (no pancreatitis); 1 patient had atrial fibrillation (unrelated to study drug) and 1 patient died after 32 months of mental deterioration and starvation (unrelated to study drug). Two patients are currently on imatinib second-line and 2 on dasatinib third-line. With a median follow-up of 39 months, the estimated probability of overall survival, progression-free survival and failure-free survival was 97%, the estimated probability of event-free survival was 91%. Conclusions: The rate of failures was very low during the first 3 years. Responses remain stable. The high rates of responses achieved during the first 12 months are being translated into optimal outcome for most of patients.

A projection into the ideas and technologies of "non-place" and "space of flow" in urban context

The meaning of a place has been commonly assigned to the quality of having root (rootedness) or sense of belonging to that setting. While on the contrary, people are nowadays more concerned with the possibilities of free moving and networks of communication. So, the meaning, as well as the materiality of architecture has been dramatically altered with these forces. It is therefore of significance to explore and redefine the sense and the trend of architecture at the age of flow. In this dissertation, initially, we review the gradually changing concept of "place-non-place" and its underlying technological basis. Then we portray the transformation of meaning of architecture as influenced by media and information technology and advanced methods of mobility, in the dawn of 21st century. Against such backdrop, there is a need to sort and analyze architectural practices in response to the triplet of place-non-place and space of flow, which we plan to achieve conclusively. We also trace the concept of flow in the process of formation and transformation of old cities. As a brilliant case study, we look at Persian Bazaar from a socio-architectural point of view. In other word, based on Robert Putnam's theory of social capital, we link social context of the Bazaar with architectural configuration of cities. That is how we believe "cities as flow" are not necessarily a new paradigm.

Cinchona alkaloids and BINOL derivatives as privileged catalysts or ligands in asymmetric synthesis

During the last fifteen years organocatalysis emerged as a powerful tool for the enantioselective functionalization of the most different organic molecules. Both C-C and C-heteroatom bonds can be formed in an enantioselective fashion using many types of catalyst and the field is always growing. Many kind of chiral catalysts have emerged as privileged, but among them Proline, cinchona alkaloids, BINOL, and their derivatives showed to be particularly useful chiral scaffolds. This thesis, after a short presentation of many organocatalysts and activation modes, focuses mainly on cinchona alkaloid derived primary amines and BINOL derived chiral Brønsted acids, describing their properties and applications. Then, in the experimental part, these compounds are used for the catalysis of new transformations. The enantioselective Friedel-Crafts alkylation of cyclic enones with naphthols using cinchona alkaloid derived primary amines as catalysts is presented and discussed. The results of this work were very good and this resulted also in a publication. The same catalysts are then used to accomplish the enantioselective addition of indoles to cyclic enones. Many catalysts in combination with many acids as co-catalysts were tried and the reaction was fully studied. Selective N-alkylation was obtained in many cases, in combination with quite good to good enantioselectivities. Also other kind of catalysis were tried for this reaction, with interesting results. Another aza-Michael reaction between OH-free hydroxylamines and nitrostyrene using cinchona alkaloid derived thioureas is briefly discussed. Then our attention focused on Brønsted acid catalyzed transformations. With this regard, the Prins cyclization, a reaction never accomplished in an enantioselective fashion until now, is presented and developed. The results obtained are promising. In the last part of this thesis the work carried out abroad is presented. In Prof. Rueping laboratories, an enantioselective Nazarov cyclization using cooperative catalysis and the enantioselective desymmetrization of meso-hydrobenzoin catalyzed by Brønsted acid were studied.

Exploring host-pathogen interactions through protein microarray. Large-scale protein microarray analysis revealed novel human receptors for the staphylococcal immune evasion protein FLIPr and for the neisserial adhesin NadA

Adhesion, immune evasion and invasion are key determinants during bacterial pathogenesis. Pathogenic bacteria possess a wide variety of surface exposed and secreted proteins which allow them to adhere to tissues, escape the immune system and spread throughout the human body. Therefore, extensive contacts between the human and the bacterial extracellular proteomes take place at the host-pathogen interface at the protein level. Recent researches emphasized the importance of a global and deeper understanding of the molecular mechanisms which underlie bacterial immune evasion and pathogenesis. Through the use of a large-scale, unbiased, protein microarray-based approach and of wide libraries of human and bacterial purified proteins, novel host-pathogen interactions were identified. This approach was first applied to Staphylococcus aureus, cause of a wide variety of diseases ranging from skin infections to endocarditis and sepsis. The screening led to the identification of several novel interactions between the human and the S. aureus extracellular proteomes. The interaction between the S. aureus immune evasion protein FLIPr (formyl-peptide receptor like-1 inhibitory protein) and the human complement component C1q, key players of the offense-defense fighting, was characterized using label-free techniques and functional assays. The same approach was also applied to Neisseria meningitidis, major cause of bacterial meningitis and fulminant sepsis worldwide. The screening led to the identification of several potential human receptors for the neisserial adhesin A (NadA), an important adhesion protein and key determinant of meningococcal interactions with the human host at various stages. The interaction between NadA and human LOX-1 (low-density oxidized lipoprotein receptor) was confirmed using label-free technologies and cell binding experiments in vitro. Taken together, these two examples provided concrete insights into S. aureus and N. meningitidis pathogenesis, and identified protein microarray coupled with appropriate validation methodologies as a powerful large scale tool for host-pathogen interactions studies.