Topical Treatment Using Amphotericin B and DMSO for an Atypically Located Equine Cutaneous Pythiosis

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at flooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdomen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes. Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left flank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomori's methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated as initial treatment, and due to financial reasons, the owners elected only the topical antifungal therapy to control the fungus infection after surgery. Flunixin meglumine was also administrated for five days aiming the control of pain and inflammation. The wound was cleaned with povidone-iodine solution and rinsed with a solution containing, 50 mg, of amphotericin B in 10 mL of sterile water and 10 mL of DMSO. This procedure was carried Out twice a day. The wound healed fast due to an excellent centripetal epithelialization. and the horse was discharged after 64 days showing only 5% of the initial wound area. The owner reported by telephone the complete healing and hair growth 10 days after discharge. Discussion: Despite the atypical location of the tumoral lesion described at the present report, the history and clinical manifestations, especially the intense pruritus, showed similarity with other characteristic reports of equine cutaneous pythiosis. The diagnosis was confirmed by the histopathological examination showing hyphae structures, as described to be evidences of the presence of Pythium insidiosum in the tissue. The surgical procedure was the first step to provide remission of clinical signs, and one day after surgery the pruritus desapeared. After excision of the granulomatous tissue and cauterization, daily topical administration of amphotericin B associated with DMSO was effective in destroying the infectious agent, as observed by the excellent epithelization. A pink granulation tissue grew up providing an ideal surface for epithelial migration and the healing process progressed quickly. Centripetal epithelialization reduced the wound area until 3% of the initial area in 64 days of treatment, when the remaining wound was found almost completely healed and covered with hair. At the present report, the horse presenting pythiosis was only topically treated. The recommended therapy using amphotericin B and DMSO solution was effective, economically viable and low risk, considering that the systemic antifungal therapy usually suggested is expensive and extremely nephrotoxic. The atypical location of the lesion on the left flank shows that any anatomical region can be affected by the fungus, since the conditions for its development were present.

ARBUSCULAR MYCORRHIZAE AND RHIZOBIUM IN ROOTING AND NUTRITION OF ANGICO-VERMELHO SEEDLINGS

The objective of this study was to evaluate the effect of inoculation of arbuscular mycorrhizae fungi (AMF) and rhizobium on rooting, growth and nutrition of seedlings of angico-red (Anadenanthera macrocarpa (Benth) Brenan) propagated by minicutting. Six progenies were used, of which were prepared cuttings with a pair of complete leaves. It was used a 55 cm(3)container filled with commercial substrate Bioplant (R). Four treatments were tested: 8 kg m-3 of superphosphate (SS) added to substrate; 4 kg m-3 SS added to substrate; 4 kg m-3 SS added to substrate and adition of a suspension solution containing rhizobium; 4 kg m-3 SS and suspension solution containing rhizobium plus 5 g of soil contaminated by AMF spores. There was no interaction among treatments for survival rate of cuttings and roots observed at bottom of the container, evaluated in the greenhouse exit (30 days) and the shade house exit (40 days), probably because the root system was still in formation. There were differences among the progeny for survival rate of the shoots, the percentage of cuttings with roots observed at bottom of the container, height, stem diameter and shoot dry weight. The evaluations of the growth characteristics of the cuttings in, particularly with respect to survival at full sun (140 days), demonstrate the efficiency of rhizobium and AMF on seedling production of this species. We conclude that the symbiotic association with rhizobium and / or FMA favors the production of seedlings of A. macrocarpa by minicutting.

Hollow-fiber liquid-phase microextraction and gas chromatography-mass spectrometry of barbiturates in whole blood samples

Here, we present a method for measuring barbiturates (butalbital, secobarbital, pentobarbital, and phenobarbital) in whole blood samples. To accomplish these measurements, analytes were extracted by means of hollow-fiber liquid-phase microextraction in the three-phase mode. Hollow-fiber pores were filled with decanol, and a solution of sodium hydroxide (pH 13) was introduced into the lumen of the fiber (acceptor phase). The fiber was submersed in the acidified blood sample, and the system was subjected to an ultrasonic bath. After a 5 min extraction, the acceptor phase was withdrawn from the fiber and dried under a nitrogen stream. The residue was reconstituted with ethyl acetate and trimethylanilinium hydroxide. An aliquot of 1.0 mu L of this solution was injected into the gas chromatograph/mass spectrometer, with the derivatization reaction occurring in the hot injector port (flash methylation). The method proved to be simple and rapid, and only a small amount of organic solvent (decanol) was needed for extraction. The detection limit was 0.5 mu g/mL for all the analyzed barbiturates. The calibration curves were linear over the specified range (1.0 to 10.0 mu g/mL). This method was successfully applied to postmortem samples (heart blood and femoral blood) collected from three deceased persons previously exposed to barbiturates.

Absorption and metabolism of volatile fatty acids by rumen and omasum

Volatile fatty acids (VFA) absorption and metabolic capacity of rumen and omasum were compared, in vitro. Fragments of rumen wall and omasum laminae were taken from eight adult crossbred bovines. An isolated fragment of the mucosa was fitted in a tissue diffusion chamber. Valeric acid and CrEDTA were added to ruminal fluid and placed on the mucosal side and buffer solution was placed on the serosal side. Fractional absorption rates were measured by exponential VFA:Cr ratio decay over time. Metabolism rate was determined as the difference between VFA absorbed and VFA which appeared on the serosal side over time. Mitotic index was higher in omasum (0.52%) than in rumen epithelium (0.28%). VFA fractional absorption rate was higher in omasum (4.6%/h.cm²) than in rumen (0.4%/h.cm²). Acetate, propionate, butyrate, and valerate showed similar fractional absorption rates in both fragments. Percentage of metabolized acetate and propionate was lower than butyrate and valerate in both stomach compartments. In the rumen, individual VFA metabolism rates were similar (mean of 7.7 , but in the omasum, valerate (90.0 was more metabolized than butyrate (59.6 propionate (69.8 and acetate (51.7 . Correlation between VFA metabolism and mitotic index was positive in the rumen and in the omasum. In conclusion, VFA metabolism and absorption potential per surface of the omasum is higher than that of the rumen. Variations on rumen and omasum absorption capacities occur in the same way, and there are indications that factors capable of stimulating rumen wall proliferation are similarly capable of stimulating omasum walls.

Existence and uniqueness of positive and nondecreasing solutions for a class of singular fractional boundary value problems

[EN] We establish the existence and uniqueness of a positive and nondecreasing solution to a singular boundary value problem of a class of nonlinear fractional differential equation. Our analysis relies on a fixed point theorem in partially ordered sets.

Bayesian Analysis of Linear Inverse Problems with Applications in Economics and Finance

In my PhD thesis I propose a Bayesian nonparametric estimation method for structural econometric models where the functional parameter of interest describes the economic agent's behavior. The structural parameter is characterized as the solution of a functional equation, or by using more technical words, as the solution of an inverse problem that can be either ill-posed or well-posed. From a Bayesian point of view, the parameter of interest is a random function and the solution to the inference problem is the posterior distribution of this parameter. A regular version of the posterior distribution in functional spaces is characterized. However, the infinite dimension of the considered spaces causes a problem of non continuity of the solution and then a problem of inconsistency, from a frequentist point of view, of the posterior distribution (i.e. problem of ill-posedness). The contribution of this essay is to propose new methods to deal with this problem of ill-posedness. The first one consists in adopting a Tikhonov regularization scheme in the construction of the posterior distribution so that I end up with a new object that I call regularized posterior distribution and that I guess it is solution of the inverse problem. The second approach consists in specifying a prior distribution on the parameter of interest of the g-prior type. Then, I detect a class of models for which the prior distribution is able to correct for the ill-posedness also in infinite dimensional problems. I study asymptotic properties of these proposed solutions and I prove that, under some regularity condition satisfied by the true value of the parameter of interest, they are consistent in a "frequentist" sense. Once I have set the general theory, I apply my bayesian nonparametric methodology to different estimation problems. First, I apply this estimator to deconvolution and to hazard rate, density and regression estimation. Then, I consider the estimation of an Instrumental Regression that is useful in micro-econometrics when we have to deal with problems of endogeneity. Finally, I develop an application in finance: I get the bayesian estimator for the equilibrium asset pricing functional by using the Euler equation defined in the Lucas'(1978) tree-type models.

Design and Performance Evaluation of Network-on-Chip Communication Protocols and Architectures

The scale down of transistor technology allows microelectronics manufacturers such as Intel and IBM to build always more sophisticated systems on a single microchip. The classical interconnection solutions based on shared buses or direct connections between the modules of the chip are becoming obsolete as they struggle to sustain the increasing tight bandwidth and latency constraints that these systems demand. The most promising solution for the future chip interconnects are the Networks on Chip (NoC). NoCs are network composed by routers and channels used to inter- connect the different components installed on the single microchip. Examples of advanced processors based on NoC interconnects are the IBM Cell processor, composed by eight CPUs that is installed on the Sony Playstation III and the Intel Teraflops pro ject composed by 80 independent (simple) microprocessors. On chip integration is becoming popular not only in the Chip Multi Processor (CMP) research area but also in the wider and more heterogeneous world of Systems on Chip (SoC). SoC comprehend all the electronic devices that surround us such as cell-phones, smart-phones, house embedded systems, automotive systems, set-top boxes etc... SoC manufacturers such as ST Microelectronics , Samsung, Philips and also Universities such as Bologna University, M.I.T., Berkeley and more are all proposing proprietary frameworks based on NoC interconnects. These frameworks help engineers in the switch of design methodology and speed up the development of new NoC-based systems on chip. In this Thesis we propose an introduction of CMP and SoC interconnection networks. Then focusing on SoC systems we propose: • a detailed analysis based on simulation of the Spidergon NoC, a ST Microelectronics solution for SoC interconnects. The Spidergon NoC differs from many classical solutions inherited from the parallel computing world. Here we propose a detailed analysis of this NoC topology and routing algorithms. Furthermore we propose aEqualized a new routing algorithm designed to optimize the use of the resources of the network while also increasing its performance; • a methodology flow based on modified publicly available tools that combined can be used to design, model and analyze any kind of System on Chip; • a detailed analysis of a ST Microelectronics-proprietary transport-level protocol that the author of this Thesis helped developing; • a simulation-based comprehensive comparison of different network interface designs proposed by the author and the researchers at AST lab, in order to integrate shared-memory and message-passing based components on a single System on Chip; • a powerful and flexible solution to address the time closure exception issue in the design of synchronous Networks on Chip. Our solution is based on relay stations repeaters and allows to reduce the power and area demands of NoC interconnects while also reducing its buffer needs; • a solution to simplify the design of the NoC by also increasing their performance and reducing their power and area consumption. We propose to replace complex and slow virtual channel-based routers with multiple and flexible small Multi Plane ones. This solution allows us to reduce the area and power dissipation of any NoC while also increasing its performance especially when the resources are reduced. This Thesis has been written in collaboration with the Advanced System Technology laboratory in Grenoble France, and the Computer Science Department at Columbia University in the city of New York.

Modeling surface-atmosphere exchange of trace gases and energy within and above the Amazon rain forest

Die vorliegende Dissertation untersucht die biogeochemischen Vorgänge in der Vegetationsschicht (Bestand) und die Rückkopplungen zwischen physiologischen und physikalischen Umweltprozessen, die das Klima und die Chemie der unteren Atmosphäre beeinflussen. Ein besondere Schwerpunkt ist die Verwendung theoretischer Ansätze zur Quantifizierung des vertikalen Austauschs von Energie und Spurengasen (Vertikalfluss) unter besonderer Berücksichtigung der Wechselwirkungen der beteiligten Prozesse. Es wird ein differenziertes Mehrschicht-Modell der Vegetation hergeleitet, implementiert, für den amazonischen Regenwald parametrisiert und auf einen Standort in Rondonia (Südwest Amazonien) angewendet, welches die gekoppelten Gleichungen zur Energiebilanz der Oberfläche und CO2-Assimilation auf der Blattskala mit einer Lagrange-Beschreibung des Vertikaltransports auf der Bestandesskala kombiniert. Die hergeleiteten Parametrisierungen beinhalten die vertikale Dichteverteilung der Blattfläche, ein normalisiertes Profil der horizontalen Windgeschwindigkeit, die Lichtakklimatisierung der Photosynthesekapazität und den Austausch von CO2 und Wärme an der Bodenoberfläche. Desweiteren werden die Berechnungen zur Photosynthese, stomatären Leitfähigkeit und der Strahlungsabschwächung im Bestand mithilfe von Feldmessungen evaluiert. Das Teilmodell zum Vertikaltransport wird im Detail unter Verwendung von 222-Radon-Messungen evaluiert. Die ``Vorwärtslösung'' und der ``inverse Ansatz'' des Lagrangeschen Dispersionsmodells werden durch den Vergleich von beobachteten und vorhergesagten Konzentrationsprofilen bzw. Bodenflüssen bewertet. Ein neuer Ansatz wird hergeleitet, um die Unsicherheiten des inversen Ansatzes aus denjenigen des Eingabekonzentrationsprofils zu quantifizieren. Für nächtliche Bedingungen wird eine modifizierte Parametrisierung der Turbulenz vorgeschlagen, welche die freie Konvektion während der Nacht im unteren Bestand berücksichtigt und im Vergleich zu früheren Abschätzungen zu deutlich kürzeren Aufenthaltszeiten im Bestand führt. Die vorhergesagte Stratifizierung des Bestandes am Tage und in der Nacht steht im Einklang mit Beobachtungen in dichter Vegetation. Die Tagesgänge der vorhergesagten Flüsse und skalaren Profile von Temperatur, H2O, CO2, Isopren und O3 während der späten Regen- und Trockenzeit am Rondonia-Standort stimmen gut mit Beobachtungen überein. Die Ergebnisse weisen auf saisonale physiologische Änderungen hin, die sich durch höhere stomatäre Leitfähigkeiten bzw. niedrigere Photosyntheseraten während der Regen- und Trockenzeit manifestieren. Die beobachteten Depositionsgeschwindigkeiten für Ozon während der Regenzeit überschreiten diejenigen der Trockenzeit um 150-250%. Dies kann nicht durch realistische physiologische Änderungen erklärt werden, jedoch durch einen zusätzlichen cuticulären Aufnahmemechanismus, möglicherweise an feuchten Oberflächen. Der Vergleich von beobachteten und vorhergesagten Isoprenkonzentrationen im Bestand weist auf eine reduzierte Isoprenemissionskapazität schattenadaptierter Blätter und zusätzlich auf eine Isoprenaufnahme des Bodens hin, wodurch sich die globale Schätzung für den tropischen Regenwald um 30% reduzieren würde. In einer detaillierten Sensitivitätsstudie wird die VOC Emission von amazonischen Baumarten unter Verwendung eines neuronalen Ansatzes in Beziehung zu physiologischen und abiotischen Faktoren gesetzt. Die Güte einzelner Parameterkombinationen bezüglich der Vorhersage der VOC Emission wird mit den Vorhersagen eines Modells verglichen, das quasi als Standardemissionsalgorithmus für Isopren dient und Licht sowie Temperatur als Eingabeparameter verwendet. Der Standardalgorithmus und das neuronale Netz unter Verwendung von Licht und Temperatur als Eingabeparameter schneiden sehr gut bei einzelnen Datensätzen ab, scheitern jedoch bei der Vorhersage beobachteter VOC Emissionen, wenn Datensätze von verschiedenen Perioden (Regen/Trockenzeit), Blattentwicklungsstadien, oder gar unterschiedlichen Spezies zusammengeführt werden. Wenn dem Netzwerk Informationen über die Temperatur-Historie hinzugefügt werden, reduziert sich die nicht erklärte Varianz teilweise. Eine noch bessere Leistung wird jedoch mit physiologischen Parameterkombinationen erzielt. Dies verdeutlicht die starke Kopplung zwischen VOC Emission und Blattphysiologie.

Detection of small buried objects: asymptotic factorization and MUSIC

In this work, we consider a simple model problem for the electromagnetic exploration of small perfectly conducting objects buried within the lower halfspace of an unbounded two–layered background medium. In possible applications, such as, e.g., humanitarian demining, the two layers would correspond to air and soil. Moving a set of electric devices parallel to the surface of ground to generate a time–harmonic field, the induced field is measured within the same devices. The goal is to retrieve information about buried scatterers from these data. In mathematical terms, we are concerned with the analysis and numerical solution of the inverse scattering problem to reconstruct the number and the positions of a collection of finitely many small perfectly conducting scatterers buried within the lower halfspace of an unbounded two–layered background medium from near field measurements of time–harmonic electromagnetic waves. For this purpose, we first study the corresponding direct scattering problem in detail and derive an asymptotic expansion of the scattered field as the size of the scatterers tends to zero. Then, we use this expansion to justify a noniterative MUSIC–type reconstruction method for the solution of the inverse scattering problem. We propose a numerical implementation of this reconstruction method and provide a series of numerical experiments.

Aspects of poriferan (Suberites domuncula) apoptosis and innate immune system and evolutionary implications

Survivin, a unique member of the family of inhibitors of apoptosis (IAP) proteins, orchestrates intracellular pathways during cell division and apoptosis. Its central regulatory function in vertebrate molecular pathways as mitotic regulator and inhibitor of apoptotic cell death has major implications for tumor cell proliferation and viability, and has inspired several approaches that target survivin for cancer therapy. Analyses in early-branching Metazoa so far propose an exclusive role of survivin as a chromosomal passenger protein, whereas only later during evolution the second, complementary antiapoptotic function might have arisen, concurrent with increased organismal complexity. To lift the veil on the ancestral function(s) of this key regulatory molecule, a survivin homologue of the phylogenetically oldest extant metazoan taxon (phylum Porifera) was identified and functionally characterized. SURVL of the demosponge Suberites domuncula shares significant similarities with its metazoan homologues, ranging from conserved exon/intron structures to the presence of localization signal and protein-interaction domains, characteristic of IAP proteins. Whereas sponge tissue displayed a very low steady-state level, SURVL expression was significantly up-regulated in rapidly proliferating primmorph cells. In addition, challenge of sponge tissue and primmorphs with cadmium and the lipopeptide Pam3Cys-Ser-(Lys)4 stimulated SURVL expression, concurrent with the expression of newly discovered poriferan caspases (CASL and CASL2). Complementary functional analyses in transfected HEK-293 revealed that heterologous expression of poriferan survivin in human cells not only promotes cell proliferation but also augments resistance to cadmium-induced cell death. Taken together, these results demonstrate both a deep evolutionary conserved and fundamental dual role of survivin, and an equally conserved central position of this key regulatory molecule in interconnected pathways of cell cycle and apoptosis. Additionally, SDCASL, SDCASL2, and SDTILRc (TIR-LRR containing protein) may represent new components of the innate defense sentinel in sponges. SDCASL and SDCASL2 are two new caspase-homolog proteins with a singular structure. In addition to their CASc domains, SDCASL and SDCASL2 feature a small prodomain NH2-terminal (effector caspases) and a remarkably long COOH-terminal domain containing one or several functional double stranded RNA binding domains (dsrm). This new caspase prototype can characterize a caspase specialization coupling pathogen sensing and apoptosis, and could represent a very efficient defense mechanism. SDTILRc encompasses also a unique combination of domains: several leucine rich repeats (LRR) and a Toll/IL-1 receptor (TIR) domain. This unusual domain association may correspond to a new family of intracellular sensing protein, forming a subclass of pattern recognition receptors (PRR).

Copper and zinc stable isotope ratios as tracers of biogeochemical processes, sources and transport of Cu and Zn in soils

Copper and Zn are essential micronutrients for plants, animals, and humans; however, they may also be pollutants if they occur at high concentrations in soil. Therefore, knowledge of Cu and Zn cycling in soils is required both for guaranteeing proper nutrition and to control possible risks arising from pollution.rnThe overall objective of my study was to test if Cu and Zn stable isotope ratios can be used to investigate into the biogeochemistry, source and transport of these metals in soils. The use of stable isotope ratios might be especially suitable to trace long-term processes occurring during soil genesis and transport of pollutants through the soil. In detail, I aimed to answer the questions, whether (1) Cu stable isotopes are fractionated during complexation with humic acid, (2) 65Cu values can be a tracer for soil genetic processes in redoximorphic soils (3) 65Cu values can help to understand soil genetic processes under oxic weathering conditions, and (4) 65Cu and 66Zn values can act as tracers of sources and transport of Cu and Zn in polluted soils.rnTo answer these questions, I ran adsorption experiments at different pH values in the laboratory and modelled Cu adsorption to humic acid. Furthermore, eight soils were sampled representing different redox and weathering regimes of which two were influenced by stagnic water, two by groundwater, two by oxic weathering (Cambisols), and two by podzolation. In all horizons of these soils, I determined selected basic soil properties, partitioned Cu into seven operationally defined fractions and determined Cu concentrations and Cu isotope ratios (65Cu values). Finally, three additional soils were sampled along a deposition gradient at different distances to a Cu smelter in Slovakia and analyzed together with bedrock and waste material from the smelter for selected basic soil properties, Cu and Zn concentrations and 65Cu and 66Zn values.rnMy results demonstrated that (1) Copper was fractionated during adsorption on humic acid resulting in an isotope fractionation between the immobilized humic acid and the solution (65CuIHA-solution) of 0.26 ± 0.11‰ (2SD) and that the extent of fractionation was independent of pH and involved functional groups of the humic acid. (2) Soil genesis and plant cycling causes measurable Cu isotope fractionation in hydromorphic soils. The results suggested that an increasing number of redox cycles depleted 63Cu with increasing depth resulting in heavier 65Cu values. (3) Organic horizons usually had isotopically lighter Cu than mineral soils presumably because of the preferred uptake and recycling of 63Cu by plants. (4) In a strongly developed Podzol, eluviation zones had lighter and illuviation zones heavier 65Cu values because of the higher stability of organo-65Cu complexes compared to organo-63Cu complexes. In the Cambisols and a little developed Podzol, oxic weathering caused increasingly lighter 65Cu values with increasing depth, resulting in the opposite depth trend as in redoximorphic soils, because of the preferential vertical transport of 63Cu. (5) The 66Zn values were fractionated during the smelting process and isotopically light Zn was emitted allowing source identification of Zn pollution while 65Cu values were unaffected by the smelting and Cu emissions isotopically indistinguishable from soil. The 65Cu values in polluted soils became lighter down to a depth of 0.4 m indicating isotope fractionation during transport and a transport depth of 0.4 m in 60 years. 66Zn values had an opposite depth trend becoming heavier with depth because of fractionation by plant cycling, speciation changes, and mixing of native and smelter-derived Zn. rnCopper showed measurable isotope fractionation of approximately 1‰ in unpolluted soils, allowing to draw conclusions on plant cycling, transport, and redox processes occurring during soil genesis and 65Cu and 66Zn values in contaminated soils allow for conclusions on sources (in my study only possible for Zn), biogeochemical behavior, and depth of dislocation of Cu and Zn pollution in soil. I conclude that stable Cu and Zn isotope ratios are a suitable novel tool to trace long-term processes in soils which are difficult to assess otherwise.rn

Potential Analysis for Hypoelliptic Second Order PDEs with Nonnegative Characteristic Form

In this Thesis we consider a class of second order partial differential operators with non-negative characteristic form and with smooth coefficients. Main assumptions on the relevant operators are hypoellipticity and existence of a well-behaved global fundamental solution. We first make a deep analysis of the L-Green function for arbitrary open sets and of its applications to the Representation Theorems of Riesz-type for L-subharmonic and L-superharmonic functions. Then, we prove an Inverse Mean value Theorem characterizing the superlevel sets of the fundamental solution by means of L-harmonic functions. Furthermore, we establish a Lebesgue-type result showing the role of the mean-integal operator in solving the homogeneus Dirichlet problem related to L in the Perron-Wiener sense. Finally, we compare Perron-Wiener and weak variational solutions of the homogeneous Dirichlet problem, under specific hypothesis on the boundary datum.

Optimization of molecular and crystalline forms of drugs, agrochemicals, pesticides in relation to activity, bioavailability, patentability and to the fabrication of polymorphs, solvates, co-crystals with green chemistry methods

This doctorate was funded by the Regione Emilia Romagna, within a Spinner PhD project coordinated by the University of Parma, and involving the universities of Bologna, Ferrara and Modena. The aim of the project was: - Production of polymorphs, solvates, hydrates and co-crystals of active pharmaceutical ingredients (APIs) and agrochemicals with green chemistry methods; - Optimization of molecular and crystalline forms of APIs and pesticides in relation to activity, bioavailability and patentability. In the last decades, a growing interest in the solid-state properties of drugs in addition to their solution chemistry has blossomed. The achievement of the desired and/or the more stable polymorph during the production process can be a challenge for the industry. The study of crystalline forms could be a valuable step to produce new polymorphs and/or co-crystals with better physical-chemical properties such as solubility, permeability, thermal stability, habit, bulk density, compressibility, friability, hygroscopicity and dissolution rate in order to have potential industrial applications. Selected APIs (active pharmaceutical ingredients) were studied and their relationship between crystal structure and properties investigated, both in the solid state and in solution. Polymorph screening and synthesis of solvates and molecular/ionic co-crystals were performed according to green chemistry principles. Part of this project was developed in collaboration with chemical/pharmaceutical companies such as BASF (Germany) and UCB (Belgium). We focused on on the optimization of conditions and parameters of crystallization processes (additives, concentration, temperature), and on the synthesis and characterization of ionic co-crystals. Moreover, during a four-months research period in the laboratories of Professor Nair Rodriguez-Hormedo (University of Michigan), the stability in aqueous solution at the equilibrium of ionic co-crystals (ICCs) of the API piracetam was investigated, to understand the relationship between their solid-state and solution properties, in view of future design of new crystalline drugs with predefined solid and solution properties.

Cooperative Cognitive Wireless Networks over TV White and Gray Spaces

Wireless networks rapidly became a fundamental pillar of everyday activities. Whether at work or elsewhere, people often benefits from always-on connections. This trend is likely to increase, and hence actual technologies struggle to cope with the increase in traffic demand. To this end, Cognitive Wireless Networks have been studied. These networks aim at a better utilization of the spectrum, by understanding the environment in which they operate, and adapt accordingly. In particular recently national regulators opened up consultations on the opportunistic use of the TV bands, which became partially free due to the digital TV switch over. In this work, we focus on the indoor use of of TVWS. Interesting use cases like smart metering and WiFI like connectivity arise, and are studied and compared against state of the art technology. New measurements for TVWS networks will be presented and evaluated, and fundamental characteristics of the signal derived. Then, building on that, a new model of spectrum sharing, which takes into account also the height from the terrain, is presented and evaluated in a real scenario. The principal limits and performance of TVWS operated networks will be studied for two main use cases, namely Machine to Machine communication and for wireless sensor networks, particularly for the smart grid scenario. The outcome is that TVWS are certainly interesting to be studied and deployed, in particular when used as an additional offload for other wireless technologies. Seeing TVWS as the only wireless technology on a device is harder to be seen: the uncertainity in channel availability is the major drawback of opportunistic networks, since depending on the primary network channel allocation might lead in having no channels available for communication. TVWS can be effectively exploited as offloading solutions, and most of the contributions presented in this work proceed in this direction.

Chemical exfoliation of graphene and its application in organic electronics and energy storage devices

Graphene, the thinnest two-dimensional material possible, is considered as a realistic candidate for the numerous applications in electronic, energy storage and conversion devices due to its unique properties, such as high optical transmittance, high conductivity, excellent chemical and thermal stability. However, the electronic and chemical properties of graphene are highly dependent on their preparation methods. Therefore, the development of novel chemical exfoliation process which aims at high yield synthesis of high quality graphene while maintaining good solution processability is of great concern. This thesis focuses on the solution production of high-quality graphene by wet-chemical exfoliation methods and addresses the applications of the chemically exfoliated graphene in organic electronics and energy storage devices.rnPlatinum is the most commonly used catalysts for fuel cells but they suffered from sluggish electron transfer kinetics. On the other hand, heteroatom doped graphene is known to enhance not only electrical conductivity but also long term operation stability. In this regard, a simple synthetic method is developed for the nitrogen doped graphene (NG) preparation. Moreover, iron (Fe) can be incorporated into the synthetic process. As-prepared NG with and without Fe shows excellent catalytic activity and stability compared to that of Pt based catalysts.rnHigh electrical conductivity is one of the most important requirements for the application of graphene in electronic devices. Therefore, for the fabrication of electrically conductive graphene films, a novel methane plasma assisted reduction of GO is developed. The high electrical conductivity of plasma reduced GO films revealed an excellent electrochemical performance in terms of high power and energy densities when used as an electrode in the micro-supercapacitors.rnAlthough, GO can be prepared in bulk scale, large amount of defect density and low electrical conductivity are major drawbacks. To overcome the intrinsic limitation of poor quality of GO and/or reduced GO, a novel protocol is extablished for mass production of high-quality graphene by means of electrochemical exfoliation of graphite. The prepared graphene shows high electrical conductivity, low defect density and good solution processability. Furthermore, when used as electrodes in organic field-effect transistors and/or in supercapacitors, the electrochemically exfoliated graphene shows excellent device performances. The low cost and environment friendly production of such high-quality graphene is of great importance for future generation electronics and energy storage devices. rn