Dissertationen zum Thema „Inorganic components“

The core of this doctoral thesis is the production of large scale pieces via powder bed Additive Manufacturing (AM) technology. The main advantage of AM is the possibility to easily produce complicated and customized shapes with great benefit in term of materials consumption, production costs and time consumed. Very few companies work in this specific field with inorganics materials. The research project has been carried out in collaboration with Desamanera srl, under a contract of apprenticeship for higher education. The company, founded as innovative startup in Rovigo since December 2014, works in the field of large scale additive manufacturing and special surface finishing, with minerals, ceramics and inorganic materials. Desamanera process allows to consolidate the powder bed composed of aggregate and binder thanks to the selective deposition of simple water. The optimization process has involved different aspects: raw materials analysis and selection (aggregates and binder), printing process improvements and post-printing treatments. All the work was carried out maintaining the proper balance between the basic research and the practical needs that a small company can have. The study of raw materials has allowed to identify the main characteristics of the various components and to find new products and suppliers, compatible with the company needs of low cost and ease of supply, even in limited quantities. The printing process optimizations have followed the goal of going to improve fundamental aspects such as the deposition of the water, the laying of the powder mix and the interfaces between the layers. At the same time, the stability and reproducibility of the entire process has been increased. Starting form printed part analysis, new post-printing treatments are been developed with the aim of increase the strength of the final material or of adding new specific properties. Finally, a general overview of the already started projects is given and new possible applications are hypothesized and suggested.

On the technical platform of hybrid organic-inorganic sol-gel, the integrated optoelectronics in the forms of heterogeneous integration between the hybrid sol-gel waveguide and the high refractive index semiconductors and the nonlinear functional doping of disperse red chromophore into hybrid sol-gel is developed. The structure of hybrid sol-gel waveguide on high index semiconductor substrate is designed with BPM-CAD software. A hybrid sol-gel based on MAPTMS and TEOS suitable for lower cladding for the waveguide is developed. The multi-layer hybrid sol-gel waveguide with good mode confinement and low polarization dependence is fabricated on Si and InP. As proof of concept, a 1 x 12 beam splitter based on multimode interference is fabricated on silicon substrate. The device shows excess loss below 0.65 dB and imbalance below 0.28 dB for both TE and TM polarization. A nonlinear active hybrid sol-gel doped with disperse red 13 has been developed by simple co-solvent method. It permits high loading concentration and has low optical loss at 1550 nm. The second-order nonlinear property of the active sol-gel is induced with corona poling and studied with second harmonic generation. A 3-fold of enhancement in the poling efficiency is achieved by blue light assisted corona poling. The chromophore alignment stability is improved by reducing the free volume of the formed inorganic network from the sol-gel condensation reaction. An active sol-gel channel waveguide has been fabricated using active and passive hybrid sol-gel materials by only photopatterning and spin-coating. An amplitude modulator based on the active sol-gel containing 30 wt.% of DR13 shows an electro-optic coefficient of 14 pm/V at 1550 nm and stable operation within the observation time of 24 days.

Thanks to European environmental rules and regulations establishment, waste recycling has become a more and more relevant problematic. For manufacturing plants, especially those producing hazardous wastes, expenses linked to waste production have drastically increased over the last decades. In the proposed work, various hazardous and non-hazardous wastes, among: soda-lime and borosilicate glass cullet, cathode ray tubes glass, exhausted lime from fume abatement systems residues, sludge and slags from ferrous and non-ferrous metallurgy, and pre-stabilized municipal solid waste incinerators ashes are used to elaborate several compositions of glass-ceramics. High-temperature treatment (minimum 800 °C) associated to a Direct Sintering process (30 min) was an efficient way to stabilize chemically the final products. The impact of each waste on the final product’s mechanical properties was studied, but also their synergies between each other, when mixed together. Statistic mixture designs enabled to develop interesting products for modern building applications, such as porous tiles and lightweight panels destined to insulation, with a purpose of fulfilling multifunctional properties.
Grazie alle regole e normative ambientali europee istituite, il riciclaggio dei rifiuti è diventato una problematica sempre più rilevante. Per gli impianti di produzione, in particolare quelli che producono rifiuti pericolosi, le spese connesse allo smaltimento sono drasticamente aumentate negli ultimi decenni. Nel lavoro proposto, vari rifiuti, pericolosi o no, vengono utilizzati per elaborare diverse composizioni di vetroceramiche. Si distinguono rottami di vetro della produzione di finestre, di contenitori farmaceutici e di tubi catodici. I rifiuti non vetrosi invece sono calce esausta da residui di sistemi di filtrazione di fumi, scorie metallurgiche da leghe ferrose e non e ceneri da inceneritori. E' presentata nel presente lavoro la ricerca di un metodo di trattamento ad alta temperatura (minima 800 ° C) efficace per stabilizzare chimicamente il prodotto finale, tramite i diversi processi di sinterizzazione diretta, sinter-cristallizzazione e vetrificazione. Sono stati studiati gli effetti di ogni rifiuto sulle proprietà meccaniche del prodotto finale, ma anche le nuove funzionalità ottenute attraverso le sinergie risultanti dalla loro miscela. Miscele calibrate hanno permesso di sviluppare prodotti interessanti per applicazioni edilizie moderne, come le piastrelle porose e pannelli leggeri destinati all’isolamento.

A technological platform based on low-temperature hybrid sol-gel method for fabrication of optical waveguides and integrated optical components has been developed. The developed chemistry for doping incorporation in the host network provides a range of refractive indexes (1.444-1.51) critical for device optimization. A passivation method for improving long-term stability of organic-inorganic sol-gel material is reported. The degradation of waveguide loss over time due to moisture adsorption from the atmosphere is drastically suppressed by coating the material with a protective thin SiO2 film. The results indicate a long-term optical loss below 0.3 dB/cm for protected waveguides. The theory of multimode interference couplers employing self-imaging effect is described. A novel approach for design of high-performance MMI devices in low-contrast material is proposed. The design method is based on optimization of refractive index contrast and width of a multimode waveguide (the body of MMI couplers) to achieve a maximum number of constructively interfering modes resulting to the best self-imaging. This optimization is carried out using 3D BPM simulations. This method was applied to design 1 x 4, 1 x 12, and 4 x 4 MMI couplers and led to a superior performance in excess loss, power imbalance in output ports, and polarization sensitivity. Taking advantage of the inherent input-output phase relations in a 4 x 4 MMI coupler, an optical 90° hybrid is realized by incorporation a Y-junction to coherently excite two ports of the coupler. A series of MMI couplers were fabricated and characterized. The experimental results are in good agreement with the design. Measured performance of the sol-gel derived MMI components was compared to analogues fabricated by other technologies. The comparison demonstrates the superior performance of the sol-gel devices. The polarization sensitivity of all fabricated couplers is below 0.05 dB.

This degree project focused on examining new possible application of near-infrared (NIR) spectroscopy for quantitative and qualitative characterization of refuse derived fuel (RDF). Particularly, two possible applications were examined as part of the project. Firstly, use of NIR hyperspectral imaging for classification of common materials present in RDF. The classification was studied on artificial mixtures of materials commonly present in municipal solid waste and RDF. Data from hyperspectral camera was used as an input for machine learning models to train them, validate them, and test them. Three classification machine learning models were used in the project; partial least-square discriminant analysis (PLS-DA), support vector machine (SVM), and radial basis neural network (RBNN). Best results for classifying the materials into 11 distinct classes were reached for SVM (accuracy 94%), even though its high computational cost makes it not very suitable for real-time deployment. Second best result was reached for RBNN (91%) and the lowest accuracy was recorded for PLS-DA model (88%). On the other hand, the PLS-DA model was the fastest, being 10 times faster than the RBNN and 100 times faster than the SVM. NIR spectroscopy was concluded as a suitable method for identification of most common materials in RDF mix, except for incombustible materials like glass, metals, or ceramics. The second part of the project uncovered a potential in using NIR spectroscopy for identification of inorganic chlorine content in RDF. Experiments were performed on samples of textile impregnated with a water solution of kitchen salt representing NaCl as inorganic chlorine source. Results showed that contents of 0.2-1 wt.% of salt can be identified in absorbance spectra of the samples. Limitation appeared to be water content of the examined samples, as with too large amount of water in the sample, the influence of salt on NIR absorbance spectrum of water was too small to be recognized.
FUDIPO

Il monitoraggio della qualità dell’aria é un primo passo attraverso un futuro migliore perché ci segnala quale processo emette più sostanze dannose nell’atmosfera e dove c’è bisogno di applicare tecnologie nuove per ridurre le emissioni. In questo lavoro, la componente organica (IPA, TC-EC-OC, levoglucosano) e quella inorganica (metalli) sono state determinate mediante il monitoraggio attivo (filtri) e il biomonitoraggio (T. aeranthos).
In this study, the organic and inorganic fraction of the airborne particulate matter was determined on a) filter devices (active sampling), and b) by biomonitoring (passive sampling). Organic components of the atmospheric particulate such as PAH, compounds out of the carbonaceous fraction, and levoglucosan, which are demonstrated to induce adverse effects on humans’ health, were detected. Further, also inorganic compounds such as As and Hg were found in some exposed samples. Monitoring the components of the air is a first step towards an increase in life quality.

The development of new methods of generating alpha-amino acid derivatives via multi-component reactions remains an important challenge. The primary goal of this study is to develop new transition metal-mediated routes to synthesize these alpha-amino acid derivatives using combinations of simple reagents, such as imines, carbon monoxide, acid chlorides and organotin reagents. The proposed approach requires the sequential insertion of imine and carbon monoxide into late transition-metal sigma-bonds, as well as the further reactivity of the products.
In chapter 2, the ability of the nickel complex L2Ni(CH 3)N(R)=C(H)R'+X- (L2 = chelating nitrogen ligands, X- = non-coordinating counteranion) to mediate the insertion of imines is examined. Although L2Ni(CH3)N(R)=C(H)R' +X- does not undergo direct imine insertion into the Ni-CH3 bond, the addition of CO leads to the generation of the novel nickel complex (L2)Ni[n2-CH(R')NRCOCH 3]+X- via the insertion of imine into the nickel-acyl bond of L2Ni(COCH3)N(R)=C(H)R' +X-. This demonstrates as proof of concept, that these nickel complexes can mediate the sequential insertion of CO and imine into nickel-methyl bonds, in direct analogy to well known CO/olefin insertions. Further reactivity studies have demonstrated that the amide bound nickel chelates generated via the sequential insertion of CO and imines are generally inert towards subsequent migratory insertion with CO, imine and olefins (Chapter 3). These complexes are also inert towards auxiliary ligand exchange or amide de-chelation, with both mono- and bidenate nitrogen and phosphine ligands.
Studies involving the use of imines and alkenes as interchangeable insertion substrates, (Chapter 4) resulted in the first example of a metal mediated cyclocarbonylation incorporating imine as a formal insertion substrate. Based on these studies, one-pot sequential insertion cascade of CO, olefin, a second unit of CO, and imine was developed for the synthesis of 5 and 6 membered lactams. In addition, the competitive insertion propensity of imines and alpha-olefins was examined, and clear steric and electronic effects were identified.
The isoelectronic palladium-bound amide complexes, generated via the oxidative addition of N-acyl iminium salts (R(H)C=N(R')COR") to Pd2(dba) 3·CHCl3 can undergo a Stille-tye coupling with organotin reagents to generate alpha-substituted amide derivatives (Chapter 5). This reactivity was extended into a convenient and general one-pot synthesis of alpha-substituted amides and N-protected amines by a palladium-catalyzed three-component coupling of imines, acid chlorides or chloroformates, and organotin reagents. Mechanistically, this process provides an oxidative addition/reductive elimination-based alternative to nucleophilic approaches to C-C bond formation with imines, in which the imines are activated towards addition to palladium by RCOCl.

Due to the strong increase in the world energy consumption, and need of exploiting carbon neutral energy sources, increasing efforts have been devoted to the exploitation of solar energy technology. For their unique properties, Dye Sensitized Solar Cells (DSSC) could complement the established silicon junctions. This Ph.D. thesis is mainly focused on the understanding of the (photo)/electrochemical properties of new components for DSSCs. The first chapter, realized in collaboration with the Prof. Stagni’s group, is about the characterization of new examples of Ru(II)-tetrazolato dyes as thiocyanate-free sensitizers for solar cell applications. Four complexes (D1-D4) have been analyzed together with the well know standard N719. The combination of the electrochemical and spectroscopic analyses revealed ground and excited states thermodynamic properties suitable for efficient interfacial charge separation. These features resulted in external quantum yield of photon to electron conversions higher than 80%. The best performances have been recorded in the case of D4 thanks to the combinations of the broader harvesting, efficient regeneration, and electron injection. Three chapters of my thesis report about the collaborative research carried out with the groups led by Dr. P.C. Gros and Dr. M.C. Pastore, involving the investigation of the electronic properties of Fe(II)NHC (NHC=N-Heterocyclic-Carbene) sensitizers. First, we tried to rationalize the charge transfer dynamics of C1 a homoleptic complex bearing σ-donating NHCs and π-accepting carboxylic groups, which initially reported rather low performances (0.13 % of PCE%). We achieved a substantial progress in cell efficiency (PCE = 1%). We estimated an injection quantum yield (Φinj) of ca. 50% that, is believed to be the main limitation for the rather low PCE. In consideration of the excited state energetics, nearly optimal for injection into TiO2, this relatively low Φinj could be due to a non-optimal electronic coupling arising from the symmetric design of the homoleptic C1. For this reason, we moved to Fe(II)NHC heteroleptic designs characterized by an asymmetric coordination sphere. The first complex was the asymmetric analogue of C1 named ARM13, while other design incorporated spacers between the anchoring moieties and the pyridine linked to the metal center, in particular, a thiophene in the case of ARM7 and a phenyl ring in the case of ARM11. The rationale behind such designs was to increase the electron-hole separation and the light harvesting capability. We were able to obtain the highest power conversion efficiency (ARM13 ca. 1.5%) ever reported for a Fe(II) sensitizer. In a third project, we designed, realized and characterized a new family of heteroleptic Fe(II)NHC complexes bearing electron withdrawing or donating substituents on the ancillary ligands. In particular, among the new series, ARM130 bearing a dimethoxyphenyl group, exhibited the best performance, thanks to its improved light harvesting capability introduced by the electron-donating -OMe moieties. We obtained a Power Conversion Efficiency of 1.83%. The last chapter of my thesis is about the investigations of alternative counter electrode (CE) materials for DSSCs based on the poly(3,4-ethylenedioxythiophene) (PEDOT) conductive polymer. The best and well-known electrocatalyst PEDOT/ClO4 (PER) involves the use of organic solvents, greener and sustainable alternative deposition routes are desirable. We explored the electrochemical properties of PEDOT/Nafion CE (NAF), produced through water- based electropolymerization. The electrocatalytic behavior of PER and NAF has been investigated in STLC by means of LSV and EIS, in the presence of either Co- or Cu- based electrolyte, NAF rivals the kinetic and mass transport properties of PER. This result was confirmed by the performance of D35 sensitized solar cells, where NAF counter electrodes generated comparable efficiency of those recorded for PER.
A causa dell’aumento della richiesta energetica e della necessità di esplorare risorse sostenibili, ingenti sforzi sono rivolti verso l’applicazione di tecnologia solare. Grazie alle loro peculiarità, le Celle Solari Sensibilizzate con Colorante (DSSCs) potrebbero essere uno strumento complementare alla tecnologia al silicio. Questa tesi di Dottorato è incentrata nella comprensione delle proprietà (foto)/elettrochimiche di nuovi componenti per DSSCs. Il primo capitolo sperimentale, realizzato in collaborazione con il gruppo del Prof. Stagni, ha avuto come scopo la caratterizzazione di nuovi sensibilizzatori di Ru(II)-tetrazolati come esempio di complessi privi di leganti tiocianati. Quattro complessi (D1-D4) sono stati studiati assieme al ben noto standard di rutenio N719. La combinazione dell’analisi elettrochimica e spettroscopica ha evidenziato come la termodinamica dello stato fondamentale ed eccitato sia in grado di favorire un’efficiente separazione di carica. Queste caratteristiche hanno portato ad una resa quantica di conversione di fotoni in elettroni superiore all’80%. D4 è risultato essere il complesso più efficiente grazie alla combinazione della più estesa estensione spettrale, efficiente rigenerazione ed efficiente iniezione di carica. Gran parte della mia attività, tuttavia, è stata rivolta allo studio di sensibilizzatori per DSSCs a base di ferro. Tre capitoli, in collaborazione con i gruppi del Dr. P. C. Gros e dalla Dr. M. C. Pastore, riportano l’investigazione delle proprietà elettroniche di sensibilizzatori di Fe(II)NHC. Nel primo di questi abbiamo studiato le proprietà di trasferimento dinamiche di un complesso omolettico denominato C1, caratterizzato da leganti NHC σ-donatori e gruppi carbossilici π-accettori, il quale aveva inizialmente restituito valori di efficienza dello 0.13%. Abbiamo ottenuto un sostanziale aumento di efficienza ottenendo valori vicini all’1%. Il rendimento quantico di iniezione di carica è risultato essere attorno al 50% e costituisce il principale fattore limitante per le DSSCs a base di ferro. L’energetica dello stato eccitato è risultata ottimale per un’efficiente iniezione di carica quindi, le limitate prestazioni esibite da C1 derivano dal suo design simmetrico che porta ad un accoppiamento elettronico non favorevole con la superficie. Abbiamo così analizzato complessi carbenici eterolettici, il primo di questi era l’analogo asimmetrico di C1, ARM13, altri due invece erano caratterizzati dall’introduzione di un anello tiofenico (ARM7) e uno fenilico (ARM11) aventi la funzione di spaziatori fra le funzionalità ancoranti e le piridine coordinate al metallo centrale. L’idea di questo nuovo design era quella di aumentare la separazione di carica ed incrementare la capacità di raccolta di fotoni. Abbiamo ottenuto la più alta efficienza di cella riportata in letteratura del 1.5% per ARM13. In un terzo progetto abbiamo analizzato una nuova famiglia di complessi eterolettici caratterizzati dall’introduzione di gruppi elettron-donatori o elettron-attrattori sui leganti ancillari. ARM130, caratterizzato da una funzionalità dimetossifenilica, ha restituito le migliori performances dell’1.83%. L’ultimo capitolo della mia tesi riguarda invece lo studio di un controelettrodo (CE) alternativo per DSSCs basato su polimeri conduttori a base di poli(3,4-etilendiossitiofene) (PEDOT), fra questi il ben noto PEDOT/ClO4 (PER), elettropolimerizzato da solventi organici, risulta essere il miglior materiale elettrocatalitico. Al fine di studiare soluzioni più sostenibile, abbiamo esplorato le proprietà elettrochimiche di CE a base di PEDOT/Nafion (NAF) prodotti in ambiente acquoso. Il comportamento elettrocatalitico di PER e NAF è stato investigato in celle simmetriche mediante LSV ed EIS e in celle solari in presenza di D35, quest’ultimo ha generato efficienze di cella comparabili a quelle registrate in presenza di PER.

Les aérosols atmosphériques jouent un rôle essentiel sur l’équilibre énergétique de la planète et ont également un impact important sur la santé humaine. Le dernier rapport d’évaluation du Groupe d’Experts Intergouvernemental sur l’Evolution du Climat (GIEC) souligne que le niveau d’incertitude du forçage radiatif des aérosols est particulièrement élevé. Ceci est principalement dû aux effets complexes et mal quantifiés des propriétés chimiques, physiques et optiques des aérosols. En particulier, une humidité relative élevée (RH) augmente la quantité de vapeur d’eau captée par les particules d’aérosol atmosphériques, ce qui modifie leurs tailles, leurs morphologies et leurs composition chimiques et donc leurs propriétés optiques. Les mesures in situ des propriétés des aérosols (coefficients de diffusion et d’absorption, distribution en taille) sont généralement obtenues dans des conditions sèches (RH <40%). Or dans l’atmosphère les aérosols existent à humidité plus importante. Il est donc essentiel de connaı̂tre l’évolution des propriétés physico-chimiques et optiques des particules d’aérosol à différentes humidités relatives, afin d’améliorer les estimations des forçages radiatifs de l’aérosol. Le but de ce travail est d’étudier l’évolution des propriétés optiques (diffusion et absorption), physiques (taille) des aérosols à différentes humidités, en s’appuyant sur des mesures de laboratoire à humidité contrôlée. Des aérosols purs ont été générés, tels que des particules de silice amorphe (SiO2 ), de chlorure de sodium (NaCl), de sulfate d’ammonium ((NH4)2SO4), de nitrate de sodium (NaNO3 ) et le chlorure de potassium (KCl). L’étude est d’abord réalisée à faible humidité relative (≈ 35% RH), ensuite, les mesures sont effectuées à une RH plus élevée (de 40 à 90%) en utilisant deux dispositifs expérimentaux différents. La vapeur d’eau captée par l’aérosol, calculée à l’aide du modèle thermodynamique E-AIM, provoque un changement de sa taille et de son indice de réfraction (RI) qui influence directement ses propriétés optiques . La relation de Zdanovskii-Stokes-Robinson (ZSR) est appliquée aux mélanges d’aérosols et comparée aux mesures expérimentales. Les écarts constatés seront présentés et devraient être utilisés pour mieux comprendre l’influence de la vapeur d’eau captée par les aérosols sur le forçage radiatif estimé par les modèles climatiques
Aerosols play vital roles in energy balance of the Earth and also have a significant impact on human health. The last assessment report by the Intergovernmental Panel on Climate Change (IPCC), states that the uncertainty in the total radiative forcing is mainly dominated by the high uncertainty in the aerosol radiative forcing. This is mainly caused by the poorly understood and quantified aerosol effects. Indeed, high relative humidity (RH), promotes water uptake by atmospheric aerosol particles, which modifies their size, morphology and chemical composition and therefore their optical properties. In-situ measurements of aerosols properties (scattering and absorption coefficients, size distribution) are usually performed at dry conditions (RH <40%). However, aerosols are present in a humid atmosphere. Knowing the physical, chemical and optical properties of the aerosol particles at ambient RH is thus crucial in order to improve the estimation of the aerosol direct radiative forcing. The aim of this work is to study the evolution of aerosols optical (scattering and absorption) and physical (size) properties at different RH. Our study is based on laboratory measurements at controlled humidity. Pure aerosols were generated, such as amorphous silica (SiO2), sodium chloride (NaCl), ammonium sulfate ((NH4)2SO4 ), sodium nitrate (NaNO3) and potassium chloride (KCl). The study was first conducted under dry conditions (≈ 35% RH), then measurements were performed at higher RH (from 40 up to 90%) using two different experimental setups. The exchange of water vapor that causes a change in size and refractive index (RI) of aerosol particles and therefore directly influences their optical properties is computed using E-AIM thermodynamic model. Zdanovskii–Stokes Robinson (ZSR) approach is applied on aerosols mixtures and compared with the experimental measurements. The discrepancies found will be presented and should be used to better understand the influence of water uptake on the aerosol radiative forcing estimated by climate models

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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Amorphous silica membranes have molecular sieving properties for the separation of hydrogen from gas mixtures at high temperature. Consequently, they are considered to be applied in separation of a shifted syngas coming out of a water-gas-shift-reactor into the syngas and hydrogen. This separation is a key to an Integrated Gasification Combined Cycle (IGCC) plant, which would allow reducing the carbon footprint in power generation industry. The main objective of this thesis was to carry out a preliminary assessment of suitability of currently available amorphous silica membranes for this separation. However, the separation properties of amorphous silica membranes reported in the open literature vary by orders of magnitude. Therefore, in the first part of this thesis the separation properties of hypothetical silica membrane with different pore size distributions were predicted from first principles. Considering different possible gas transport mechanisms, it was concluded that gas transport in amorphous silica membranes is dominated by the activated and non-activated Knudsen diffusion. The activation energy for transport of different species was predicted using the concept of suction energy. Then, with arbitrary pore size distributions gas permeance of hypothetical silica membrane was predicted for different gas species. Since the pore size distribution of amorphous silica membrane cannot be known a priori, the developed model was used to determine the pore size distribution based on experimentally measured single gas permeances of three different species (kindly provided by Natural Resources Canada, CANMET Energy Technology Center (CETC) laboratory in Ottawa) by minimizing the error of the calculated permeance ratios with respect to the experimental values. The results indicate that, depending on how the objective function is defined, more than one pore size distribution can be found to satisfy the experimental permeance ratios. It is speculated that by increasing the number of experimentally determined permeances, a more unique pore size distribution for the tested silica membrane can be obtained. However, even at this early stage, the developed model provides a rational explanation for the effect of membrane densification on the properties of silica membranes. More specifically, a simultaneous decrease in membrane permeance and selectivity due to membrane densification, reported in the literature, is explained by shrinking the size of pores beyond a certain critical value, which depends on the kinetic diameter of gas molecules that are being separated. Comparing theoretically determined permeances, which match experimentally observed permeance ratios, revealed that the experimental permeances are considerably smaller than the theoretical values. The ratio of the two provided the basis for a scaling factor, a new concept that was introduced in this thesis. To simulate membrane module performance, a novel approach was introduced. More specifically, co- and counter-current flow configurations as well as cross-flow configuration were modeled by assuming no change in feed composition over an infinitesimally small element of membrane area. This led to a system of linear, rather than differential equations, which was readily solved numerically.

Most of the biological systems in nature are sustained by molecular self-assemblies which are the finest examples of supramolecular architectures. Non-covalent interactions are key concepts which govern these molecular assemblies. Inspired by these examples crystal engineering emerged as an important tool in supramolecular chemistry which aids in the invention of new molecular structures with desired properties. Understanding of how the molecules interact at the molecular levels enables one to rationally design novel solid forms with modulated physicochemical properties. This feature of crystal engineering has heightened its position in materials chemistry and is currently one of the most well studied fields for generating novel compounds with pre-defined composition and supramolecular architectures. One such class of compounds that has immensely attracted the scientific community and is under continuous study for wider applications is cocrystals. The applications include various interdisciplinary fields such as pharmaceutics, catalysis, organic conductors, explosives etc. Distinctly on the other side, cocrystals also provide a means to discover new supramolecular synthons which is the ultimate key to molecular assembly. Many robust supramolecular synthons have been discovered and hierarchies are also being developed which can serves as a design tool for cocrystal synthesis. The Cambridge Structural Database (CSD) is an important accessory in determining the robustness of a supramolecular synthon but, this does not preclude us from discovering new synthons. The work presented here explores new persistent supramolecular synthons in polyphenols utilizing the basic concepts of crystal engineering and the CSD statistical analysis. This contribution also includes the implementation of cocrystallization for various categories of compounds which includes nutraceuticals, pharmaceuticals and ionic salts for the design and synthesis of molecular and ionic cocrystals. Chapter 1 highlights how supramolecular synthon approach can be used to design and synthesize multi-component crystals, namely, cocrystals. The role of the CSD and its importance in crystal engineering has also been discussed. Chapters 2 and 3 focus on new persistent supramolecular synthons in the context of nutraceuticals. The cocrystals isolated in the study are also compared with the existing cocrystals in the CSD supramolecularly in terms of synthon formation. These persistent supramolecular synthons are helpful in developing hierarchies which could be utilized and applied to similar and analogous compounds. The main feature of Chapter 4 is expanding the field of cocrystallization by studying the properties of cocrystals. Some of the properties which have been examined here include effects of cocrystallization on solubility and correlations between the solubility of cocrystal with cocrystal former (CCF) and melting point of the cocrystal. The extension of cocrystals to the active pharmaceutical ingredients (APIs) has been explored in the context of pharmaceutical cocrystals by selecting a BCS class IV drug, hydrochlorothiazide in Chapter 5. Chapter 6 highlights the hybridization of organic and inorganic components for the synthesis of ionic cocrystals and is exemplified by considering lithium salts with achiral and homochiral amino acids for the generation of 1:1 and 1:2 cocrystals.

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Capes
At physiological maturity the seeds acquire their greatest physiological potential. From this point quantitative and qualitative losses occur as a function of seed deterioration. The deterioration is dependenton the cultivar, the climatic conditions and the time in which the seeds remain in the field until the harvest. The study of cultivars that present greater tolerance to adverse climatic conditions that maintain the productivity and the physiological quality of the seeds is of fundamental importance to understandthe mechanisms of tolerance to the delay of the harvest. The objective of this work was to verify if genotypes of beans respond differently on the yield, germination and vigor of the seeds harvested at different times of harvest; Determine the biochemical composition of the ean seeds at different times of harvest and the pattern of hydrolysis and mobilization pf the reserves during the germination process can explain the differences in vigor. The experiment was conducted in the municipality of Lages, SC, using experimental design in randomized blocks, subdivided plots and four replocates. The cultivars used were the BAFs (Active bank and germplasm): 13, 47, 55 and 57, (C18), 13% moisture (C13), and 10 days after the third harvest (C13 + 10) were collected at physiological maturity (MF). The yield, yield components, plant morphological characteristics, germination, vigor (accelerated aging) in the four genotypes and in the four harvest seasons were determined. For the evaluation of the biochemical composition (total protein, soluble protein, starch, soluble sugar, total phosphorus, phytate, inorganic phosphorus), BAFs 55 and 57 were used in the C13 and C13 + 10 harvests. The aid of the statistical programs Assistatand R. Productivity was not influenced by the harvest season; The insertionheight of the first legume and number of legumes per plant decreased with the havest delay. The physiological quality of the seeds was dependent on the harvest period. Genotype 55 maintained its physiological quality at different harvesting times, while the other genotypes showed a decrease with harvest delay in relation to physiological maturity, BAF 57 showing a greater reduction in the physiological quality of their seeds. At zero point (dry seeds) there was positive correlation of soluble sugar with accelerated aging, and negative correlation on phytate and total protein with germination. The higher efficiency in the user of phytate and inorganic phosphorus during the germination process is associated with higher vigor seeds. BAF55 showed the best performance in maintaining the quality of its seeds after physiological maturity
Na maturidade fisiológica as sementes adquirem o seu maior potencial fisiológico. A partir deste ponto ocorrem perdas quantitativas e qualitativas em função da deterioração das sementes. A deterioração é dependente da cultivar, das condições climáticas e do tempo em que as sementes permanecem no campo até a colheita. O estudo de cultivares que apresentam maior tolerância a condições climáticas adversas, que mantenham a produtividade e a qualidade fisiológica das sementes é de fundamental importância para entender os mecanismos de tolerância ao atraso da colheita. O objetivo deste trabalho foi verificar se genótipos de feijão respondem diferentemente no rendimento, germinação e o vigor das sementes colhidas em diferentes tempos de colheita; determinar a composição bioquímica das sementes de feijão nos diferentes tempos de colheita e o padrão de hidrólise e mobilização das reservas durante o processo de germinação podem explicar as diferenças quanto ao vigor. O experimento foi conduzido no município de Lages, SC, usando delineamento experimental em blocos ao acaso, parcelas subdivididas e quatro repetições. As cultivares crioulas utilizadas foram os BAFs (Banco ativo de germoplasma do CAV-UDESC): 13, 47, 55 e 57; as colheitas foram realizadas na maturidade fisiológica (MF), sementes com 18% de umidade (C18), 13% de umidade (C13) e 10 dias após a terceira colheita (C13 + 10). Determinou-se à produtividade, componentes do rendimento, características morfológicas da planta, germinação, vigor (envelhecimento acelerado) nos quatro genótipos e nas quatro épocas de colheita. Para a avaliação da composição bioquímica (proteína total, proteína solúvel, amido, açúcar solúvel, fósforo total, fitato, fósforo inorgânico) foram utilizados os BAFs 55 e 57 nas colheitas realizadas em C13 e C13 + 10. A análise dos dados foi realizada com o auxílio dos programas estatísticos Assistat e R. A produtividade não sofreu influência da época de colheita; a altura de inserção do primeiro legume e número de legumes por planta diminuíram com o atraso da colheita. A qualidade fisiológica das sementes foi dependente da época de colheita. O BAF 55 manteve sua qualidade fisiológica nas diferentes épocas de colheita, enquanto os demais genótipos apresentaram decréscimo com o atraso da colheita em relação à maturidade fisiológica, o BAF 57 apresentando maior redução da qualidade fisiológica de suas sementes. No ponto zero (sementes secas) houve correlação positiva de açúcar solúvel com envelhecimento acelerado, e correlação negativa de fitato e proteína total com germinação. A maior eficiência na utilização do fitato e do fósforo inorgânico durante o processo de germinação esta associada às sementes de maior vigor. O BAF 55 apresentou o melhor desempenho na manutenção da qualidade das suas sementes após a maturidade fisiológica

The present PhD thesis, entitled: "Essential oil components encapsulated in mesoporous silica supports: a bioactive properties evaluation and a toxicological approach" focuses on the study of protection and controlled release of natural bioactive agents, derived from essential oil components (EOCs), encapsulated in mesoporous silica particles (MSPs). In addition, this thesis evaluatesthe silica-based supports to reduceundesirable sensorial propertiesandfor ensuring a low-health risk. The first section of the thesis shows the effect of encapsulation of EOCs in mesoporous silica supports. This study evaluates the efficiency of free and encapsulated EOCs to reduce the viability of cancer colon cell lines. This sectionalso shows the selectivity of encapsulated EOCs against cancer linesandtheir effect onnormal (non-cancer) colon cells. Results indicate that EOCs effect can be enhanced and sustained in time when EOCs are encapsulated. Moreover, EOCs' encapsulation shows promising specificity indices, reaching to double effect on colon cancer cells above normal cells. On the other hand,the encapsulation supports and their surface functionalization allows the odour masking of high volatility EOCs. Therefore, the delivery system based on MSPs represents an excellent alternative to promote controlled EOCs release, taking advance of their bioactive properties and solving the technical disadvantages related to volatility and unpleasant odours. Finally, samples used for garlic components encapsulation were immobilised in nanofibers to provide homogeneous and easy-to-handle hybrid system for controlling delivery.The developed 'composite' has potential applications on food, pharmacology, medical or engineering fields. The second sectionof the thesis evaluates the toxicity of the mesoporous silica supports through in vitro and in vivo assessments. Cell viability allows to identify the cytotoxic impact based on the kind of silica-based support, and their features (doses range, size and surface structure changes). Furthermore, the use of Caednorhabditis elegansmodel,shows the in vivo effects afterMSPs ingestion. The toxicological study confirms that size and surface structure, are decisiveMSPs' featuresfor reducing the toxicity risks for health. In summary, the present thesis evaluates the mesoporous silica-based particles as supports for EOCs encapsulation and identifies the main MSPs' features forreducingthe health-toxicity impact. Results of this thesis show that MSPs improve the EOCs activity and help to solve technical problemsof EOCs' volatility.Moreover, these results open up a suitable and safety option for oral delivery devices.
La presente tesis titulada: "Componentes de aceites esenciales encapsulados en soportes mesoporosos de sílice: una evaluación de sus propiedades bioactivas y un enfoque toxicológico" se centra enla evaluación de las propiedades funcionales y organolépticas de agentes naturales bioactivos, derivados de componentes de aceites esenciales, encapsulados en materiales mesoporosos de sílice; a la vez que evalua la toxicidad de los soportes utilizados,con el fin de proponer nuevos sistemas de liberación controlada por vía oral. La primera sección de esta tesis muestra el efecto de la encapsulación de los compuestos de aceites esenciales (EOCs, por sus siglas en inglés) en soportes mesoporosos de sílice. Por un lado, seevalúa la eficiencia de los EOCs libres y encapsulados para reducir la viabilidad en líneas celulares de cáncer de colon. Además, se evalúa la selectividad de los EOCs frente a células de colon normales (líneas no tumorales). Por otro lado, seestudia la capacidad de enmascaramiento de olor de los soportes. Los resultados obtenidos, evidencian en primer lugar, que los EOCs encapsulados mejoran su actividad frente a células de cáncer,en comparacióncon la respuesta de los compuestos sin encapsular. La encapsulación hace que el efecto de los EOCs sea sostenido en el tiempo, y muestra índices de especificidad prometedores, cuandose evalua el efecto toxico de los EOCsfrente a células de cáncer de colon y células normales. Los resultados de esta primera sección, indican que los soportes basados en partículas de sílice mesoporosa (MSPs, por sus siglas en inglés) protegen y liberan eficientemente los compuestos, sino que, a la vez que la funcionalización de la superficie de las MSPs permite enmascarar el olor de los compuestos de mayor volatilidad, y con mayores inconvenientes a nivel sensorial (p.e. compuestos derivados del ajo). Por lo tanto, el sistema de encapsulación se plantea como una excelente alternativa para (i) promover la liberación controlada de EOCs, (ii) aprovechar y mejorar el efecto de sus propiedades bioactivas en células de cáncer de colón y (iii) controlar las desventajas técnicas relacionadas con la volatilidad y limitaciones organolepticas. Por último, se ha comprobado que los soportes empleados en la encapsulación de los compuestos derivados de ajo, mantienen su funcionalidad luego der ser inmovilizados en nanofribras de nylon.Con esto, se busca desarrollar un nuevo sistema de 'composite';un material híbrido y homogéneo, fácil de manejar, que libera controladamente los compuestos encapsulados desde soportes tipo fibras (composites).Estoexpande el abanico de aplicaciones de los EOCs en laindustria alimentaria y farmacológica. La segunda sección de esta tesis, evalúa la toxicidad de los soportes de sílice mesoporosa (MSPs) mediante ensayos in vitro e in vivo. En primer lugar, la viabilidad celular permite identificar el impacto citotóxico de los MSPs sobre líneas celulares de colón. En particular, se evalúa los soportes mesoporosos de sílice, tipo MCM41, en función de (i) las dosis empleadas, (ii) la diferencia de tamaño (micro y nanopartículas) y (iii) el efecto que la funcionalización de la superficie genera en la viabilidad celular. Por otro lado, empleando el modelo Caednorhabditis elegans, yadministrando por vía oral las MSPs,se evalua la influencia de las características de laspartículas (MSPs) en función de la esperanza de vida (lifespan) y la calidad con la que viven y envejecen (healthspan) los nematodos. Los resultados de este estudio,muestran que el tamaño y la estructura de la superficie de las partículas, son parámetros determinantesal momento de diseñar soportes de bajoriesgo toxicológico. En resumen, la presente tesis ha evaluado las características de la sílice mesoporosa, micro y nanoparticulada, como soporte de encapsulación para mejorar la actividad y las aplicaciones de los compuestos de aceites esenciales, al mismo tiempo
La present tesi titulada: "Components d'olis essencials encapsulats en suports mesoporosos de sílica: una avaluació de les seves propietats bioactives i un enfocament toxicològic" se centra en estudis de protecció i alliberament controlat d'agents naturals bioactius, derivats de components d'olis essencials, encapsulats en materials mesoporosos de sílica. Els components d'olis essencials encapsulats milloren les seves propietats funcionals i redueixen els problemes sensorials per aplicacions futures, garantint, al mateix temps, la baixa toxicitat dels suports desenvolupats. La primera secció de la tesi mostra l'efecte d'encapsulació dels components d'olis essencials (EOCs, per les seves sigles en anglès) en suports mesoporosos de sílica sobre la millora de les seues propietats bioactives i el camuflament de problemes sensorials. Este estudi avalua l'eficiència dels EOCs lliures i encapsulats per a reduir la viabilitat en línies cel¿lulars de càncer còlon. A més, la selectivitat dels EOCs es va provar enfront de cèl¿lules de còlon normals (no canceroses). Els resultats han demostrat que l'efecte dels EOCs pot ser millorat i sostingut en el temps quan els EOCs estan encapsulats. Encara més, l'encapsulació dels EOCs mostra índexs d'especificitat prometedors, arribant a duplicar la toxicitat en l'efecte en les cèl¿lules de càncer de còlon amb comparacio en les cèl¿lules normals. Els resultats també mostren que els suports basats en partícules de sílice mesoporoses (MSPs, per les seves sigles en anglès) no sols protegixen i alliberen EOCs eficientment, sinó que, a més, la funcionlització en superfície de les MSPs permet emmascarar l'olor dels EOCs d'alta volatilitat, que té una aplicació limitada a causa dels seus problemes sensorials(p.e. compostos derivats de l'all). Per tant, el sistema de subministrament proposat resulta una excel¿lent alternativa per a (i) promoure l'alliberament controlat de EOCs, (ii) avançant en les seues propietats bioactives en cel¿lulas de càncer còlon i (iii) controlant els desavantatges tècnics relacionats amb la volatilitat i la disseminació desagradable de les olors. Finalmet, les mostres utilitzades per encapsulació de compostos d'all es van immobilitzar en nanofibres per a proporcionar un sistema híbrid homogeni i fàcil de manejar amb administració controlada i característiques bioactives, per aplicacions potencials en l'àrea d'alimentació, farmacologia, medicina o enginyeria. La segona secció avalua la toxicitat del suports de sílice mesoporosa per mitjà d'avaluacions in vitro e in vivo. La viabilitat cel¿lular permet identificar l'impacte citotòxic basat en el tipus de suport base de sílice i les seues característiques (rang de dosi, grandària i canvis en l'estructura superficial).A més, utilitzant el model in vivo Caednorhabditis elegants, s'ha estudiat la influència de les característiques de la sílice mesoporosa, administrant micro i nanopartícules de base sílice, no sols en l'esperança de vida, sinó també en el comportament dels nematodes durant el seu envelliment. Aquest estudi ha demostrat que la grandària i l'estructura superficial, són decisius per a reduir el risc de toxicitat dels suports de sílice mesoporosa i obrir la possibilitat d'utilitzar estos materials en aplicacions d'ingesta oral. En resum, la present tesi ha avaluat les característiques de les partícules de sílice mesoporosa, com a suports d'encapsulació per a millorar l'activitat i les aplicacions dels EOCs, alhora que es va avaluar el seu principal risc tòxicologic. En conseqüència, els resultats obrin una opció adequada i de seguretat per als dispositius d'administració oral.
Acosta Romero, C. (2017). Essential oil components encapsulated in mesoporous silica supports: a bioactive properties evaluation and toxicological approach [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/90653
TESIS

Orientadores: Afonso Celso Vigorito, Maria Elvira Pizzigatti Corrêa
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Recentemente, a quantificação do fluxo salivar e dos componentes bioquímicos da saliva, foram considerados possíveis biomarcadores para a patogênese da doença do enxerto contra o hospedeiro crônica (DECHc) oral em pacientes submetidos ao Transplante de Células Tronco Hematopoiéticas (TCTH). O objetivo deste estudo foi avaliar prospectivamente a composição inorgânica salivar em diferentes períodos do transplante alogênico e no diagnóstico da DECHc e correlacioná-los com as manifestações clínicas orais. A saliva não estimulada foi coletada para determinação de fluxo salivar e das concentrações de cálcio (Ca), fosfato (Pi), cloro (Cl), magnésio (Mg), potássio (K) e sódio (Na), utilizando reações colorimétricas e absorção atómica. Os Índices de saúde bucal, mucosite e DECHc orais foram avaliados por exame clínico odontológico. A hiposalivação foi avaliada por parâmetros visuais e os pacientes responderam a um questionário sobre xerostomia, dor oral e sensibilidade. Foram incluídos no estudo, consecutivamente, 55 pacientes submetidos ao primeiro TCTH alogênico. Destes 55 pacientes, 49 (89%) foram reavaliados entre os dias D+ 8 e D+10 e 6 (11%) pacientes foram a óbito antes desse período. Após a avaliação entre os dias D+ 8 e 10, 2/ 49 (4%) pacientes recaíram, 13/49 (27%) foram a óbito 34/49 (69%) pacientes permaneceram vivos até o final deste estudo. Dos 34 pacientes 28 (82%) foram avaliados entre os dias D+ 80 e D+ 100, sem o diagnóstico de DECHc, e 12/ 34 (35%) pacientes avaliados no momento do diagnóstico da DECHc, com mediana de dias do diagnóstico de 110 (68-412). A avaliação da saúde bucal entre os dias 8 e 10 apresentou mediana do índice gengival (IG) maior quando comparada com os dados do pré-TCTH (p=0,03). Os índices Dentes Cariados, Perdidos e Obturados (CPOD), Índice de Placa (IP) e o (IG) não apresentaram qualquer alterações nos períodos do estudo. De 49 pacientes, 32 (65%) apresentaram mucosite grau 2 a 4 e a frequência foi maior ao condicionamento de altas doses (p=0,03) e nos pacientes mais jovens (p=0,02). Entre os dias 8 e 10 a queixa de dor oral foi maior nos pacientes mais jovens e no condicionamento de altas doses, (p=0,03) e (p=0,02), respectivamente. O fluxo salivar foi significativamente maior entre os dias 8 e 10 (p=0,05) em comparação ao pré-TCTH. O Pi diminuiu entre os dias 8 e 10 dias (p=0,007) e as concentrações de Na e Cl aumentaram entre os dias 8 e 10 (p=0,001 para ambos). O fluxo salivar no mesmo período demonstrou correlação negativa com a concentração de Pi (p=0,02) e positiva com as concentrações de Na e Cl, (p=0.003) e (p=0.001), respectivamente. Pacientes submetidos ao condicionamento de altas doses apresentarem menores concentrações de Pi (p=0,05). Entre os dias 80 e 100, a xerostomia foi mais frequente nos pacientes submetidos ao condicionamento com altas doses, comparada com de baixa dose (p=0,05). O fluxo salivar foi significativamente menor entre os dias 80-100 (p=0,02) em comparação com o pré-TCTH e as concentrações de Na, Cl e K aumentaram entre 80-100 dias (p=0,03), (0,02) e (p=0,003), respectivamente. O fluxo salivar no mesmo período demonstrou correlação negativa com as concentrações de Na e Cl, (p=0.01) e (p=0.013), respectivamente. Pacientes submetidos ao condicionamento de altas doses apresentaram menor concentração de Na (p=0.05), enquanto que os pacientes que receberam condicionamento de baixas doses apresentaram maiores concentrações de Na e Pi (p=0.05),( p=0,04), respectivamente. No momento do diagnostico da DECHc, o fluxo salivar não mostrou diferença estatística significativa entre os períodos do estudo. Foi observada um tendência de maior concentração de Na no diagnóstico da DECHc (p=0,06) e diminuição significativa da concentração de Pi (p=0.004) em comparação com o pré-TCTH. As concentrações de cálcio e magnésio não apresentaram qualquer alteração durante o mesmo período avaliado. O presente estudo mostrou alterações nos componentes salivares inorgânicos em períodos pós-TCTH, principalmente durante a inflamação da cavidade oral, como mucosite e DECHc. Nós podemos especular que o sódio, cloreto, fosfato e, na saliva, pode ser utilizado como um biomarcador potencial de atividade inflamatória oral em estudos posteriores
Abstract: Recent studies have considered the qualitative and quantitative assessment of salivary flow, as well the biochemical components of saliva, as possible biomarkers that might contribute to the pathogenesis of chronic Graft-Versus-host-Disease (cGHVD) in HSCT patients. The aim of this study was to evaluate the inorganic salivary status at different periods of allogeneic HSCT and cGVHD onset, prospectively. Patients were evaluated in pre-HSCT, between the days 8 and 10, 80 and 100 days without cGVHD, and at the onset of oral cGVHD. Oral health indexes, mucositis, and oral cGVHD were prospectively evaluated by oral clinical examination. Hyosalivation was clinically evaluated by visual parameters, and patients answered a questionnaire concerning xerostomia, oral pain and sensitivity. Unstimulated saliva was collected to determine the salivary flow rate and the concentrations of Calcium (Ca), Phosphate (Pi), Chloride (Cl), Magnesium (Mg), Potassium (K), and Sodium (Na) using colorimetric reactions and atomic absorption. Fifty-five consecutive patients undergoing first allogeneic HSCT were included in this study. Forty-nine out of 55 (89%) patients were evaluated between the days 8 and 10, and 6 (11%) had died before the evaluation. After the evaluation between 8 and 10 days, 2 out of 49 (4%) patients relapsed, 13 out of 49 (27%) patients died and thirty-four out of 49 (69%) patients remained alive until the end of the study. Twenty-eight out of 34 (82%) patients were evaluated between days 80 and 100 without cGVHD, and twelve out of 34 (35%) were evaluated at oral cGVHD onset, at a median time of 110 days (68-412). Oral health evaluation between the days 8 and 10 showed a higher median of Gingival Index (GI) compared with baseline data (p=0.03), and the Decayed, Missing and Filled Teeth Index (DMFT) and Plaque Index (PI) presented no statistical difference. Thirty-two out of 49 (65%) patients developed grade 2-4 oral mucositis associated with a high dose conditioning regimen (p=0.03) and younger patients (p=0.02). Between the days 8 and 10 younger patients and those who received high dose conditioning had more oral pain (p=0.03) and (p=0.02), respectively. The salivary flow rate was significant higher compared with the baseline between days 8 and 10 (p=0.05), Pi concentration was decreased, (p=0.007) and Na and Cl were increased (p=0.001), (p=0.001), respectively. The analysis of the salivary flow rate during the same period showed a negative correlation with Pi concentration (p=0.02) and a positive correlation with Na and Cl concentration, (p=0.003) and (p=0.001), respectively. Patients who received a high dose conditioning regimen presented a lower Pi concentration (p=0.05), and regardless of the conditioning regimen, no other biochemical component showed statistical difference. Xerostomia was more frequent between the days 80 and 100 in high dose, compared with reduced dose conditioning (p=0.05). The salivary flow rate was decreased between days 80 and 100 (p=0.02) and Na, Cl and K concentration was increased, (p=0.03), (p=0.02) and (p=0.003), respectively. The analysis of the salivary flow rate during the same period showed a negative correlation with Na and Cl, (p=0.01) and (p=0.013), respectively. Patients who received high dose conditioning regimen presented a lower Na concentration (p=0.05), whereas those who underwent a reduced dose conditioning regimen presented higher Na and Pi concentrations (p=0.05),( p=0,04), respectively. No other statistical difference was detected in the other biochemical components regardless of the conditioning regimen. At cGVHD onset, the salivary flow rate showed no statistical difference compared with the other periods. A trend was observed in the higher Na concentration compared with the baseline (p=0.06) and Pi concentration presented a significant decrease (p=0.004). Ca and Mg concentrations showed no changes during all evaluation periods. The present study showed changes in inorganic salivary components in post-HSCT periods, mainly during oral cavity inflammation, such as mucositis and cGVHD. We speculate that Na, Cl, and Pi in saliva could be used as a potential biomarker for oral inflammatory activity in further studies
Doutorado
Clinica Medica
Doutora em Clínica Médica

This PhD thesis is dedicated to the preparation, characterisation and biological application of gold nanoconjugates. Gold nanoparticles are prepared by various modern preparation methods, and subsequently characterised by spectroscopic (UV-vis, ATR-FTIR, NMR), microscopic (TEM) techniques. The stability of the conjugates is evaluated both by using Zeta-potential studies and UV-vis. The nanoparticles are used in cellular uptake experiments using human glioblastoma cancer cells, and are found to possess a low cytotoxicity. The nanoparticles are found taken up by the cells and distributed in different cellular compartments.

il progetto di ricerca descritto nel presente lavoro di tesi si è focalizzato sulla progettazione, sintesi e caratterizzazione di strutture 3D supramolecolari ottenute mediante appropriata combinazione di leganti piridinici con pannelli metallaciclici di zinco porfirine. La versatilità dell'approccio sintetico perseguito, ha permesso, a seguto di un astuto e pensato design delle unità di base molecolari, di ottenere efficientemente una libreria di elaborate strutture supramolecolari tridimensionali, di modulabile forma e dimensione del sistema desiderato, regolandone le proprieta fotoindotti inter-componente e/o introducendo nuove funzionalità derivanti dall'organizzazione geometrica di un preciso numero di centri metallici attivi. Parte del lavoro è stato dedicato ad una approfondita investigazione sulla possibilità di ottenere strutture eterometalliche di ordine discreto, mediante autoassemblaggio di un metallaciclo di zinco porfirine in combinazione con appropriati leganti clatrochelati piridinici, tramite una collaborazionecon il gruppo di Prof. K. Severin (EPFL di Losanna). Lo scopo finale è di ottenere facilmente, mediante un approccio sintetico modulare, sistemi funzionali di ordine superiore contenenti un definito numero di ben organizzati centri metallici attivi (cioè magneticamente, cataliticamente o redox attivi). Ci si è inoltre concentrati sulla sintesi di architetture supramolecolari discrete aventi dimensioni e geometria modulabile e recanti un numero variabile di unità porfiriniche, ottenute per semplice mescolamento di due o tre diversi moduli porfirinici. Scegliendo in modo appropriato i connettori piridinici, cioè variandone il numero di centri basici donatori e/o giocando sulla loro posizione relativa, strutture molecolari di dimensioni implememntate diventano facilmente ottenibili. Progettando in modo studiato le unità molecolari di base, in termini di lablità/inerzia e discriminazione di tipo hard/soft, queste si autoassembleranno a formare in modo quantitativo tramite la formazione di legami di coordinazione complementari. Le strutture multi-porfiriniche così ottenute costituiscono un telaio ben ordinato di unità cromoforiche coinvolti in processi fotoindotti di trasferimento di energia e di trasferimento di carica. Infine parte del lavoro di ricerca è stato svolto durante un periodo di 6 mesi trascorsi presso il laboratorio del Dr. Romain Ruppert dell’Università di Strasburgo. Il progetto aveva lo scopo di sintetizzare dei dimeri di zinco porfirine connesse mediante coordinazione a un catione di Pd(II), e di studiare la loro possibile applicazione ed utilizzo come piattaforme fotoattive alternative per l’autoassemblaggio di sistemi discreti suprmaolecolari a forma di sandwich. Da un punto di vista fotofisico il nuovo dimero presenta interessanti proprietà in quanto è presente una forte comunicazione elettroinica fra le due porfirne attraverso il ponte metallico di Pd(II). D’altro canto, da un punto di vista di sintesi supramolecolare, il dimero presenta le caratteristiche richieste: due punti di ancoraggio costituiti dai due centri di Zn(II), un buon grado di inerzia del legame esociclico e una sufficiente coplanarità a disposizione rigida delle componenti.
The research carried out during this PhD project and reported in this Thesis is focused on the design, preparation and characterization of multi-component supramolecular 3D architectures obtained by appropriate paneling multitopic pyridyl ligands with flat Zn-porphyrin metallacycles. The versatility of the synthetic approach pursued, allowed to efficiently construct libraries of elaborated 3D structures, tuning the shape and dimension of the target systems, modulating the inter-component photo-induced properties and/or introducing new functions deriving from the geometrical organization of a precise number of active metal centers, by cleverly tailoring the molecular building blocks. In Chapter 1, a general introduction on key role of porphyrins as functional and structural building unit for the assembly of artificial discrete supramolecular structures is presented, together with the main designing concepts of the metal mediated self-assembling synthetic strategy. Few examples of elegant multiporphyrin architectures and their application are reported. Finally, the modular synthetic approach pursued during this research project is described. In Chapter 2, a thourough investigation on the possibility to produce new hetero-multimetallic ordered discrete structures, by self-assembling of a zinc-porphyrin metallacycle (1Zn) with dipyridyl clathrochelate metalloligands (provided by the group of Prof. K. Severin, EPFL, Lausanne, CH), is discussed. In particular, linear FeII metal containing ligands with terminal 4-pyridyl groups, lengthes between 1.5 and 3.2 nm, and containing either one or two clatrochelate cores were chosen. The final aim is the easy access, by a modular approach, to higher order functional systems comprising defined numbers and spacial organizations of metal-active centers (e.g. magnetically, redox or catalytically active). Chapter 3 reports on the metal mediated assembling of a linear dipyridyl diazadioxa[8]circulene (Circ, provided by the group of Prof. M. Pittelkow, University of Copenhagen, DK) with either 1Zn and of a cis-protected diphosphines PtII complex. Circ is a flat and conjugated compound presenting a central antiaromatic cyclooctatetraene core. The designing idea was to endow the ligand in structures, enforcing conformations which could enable, to find experimental evidences of the antiaromaticity, by observation of deshielding effect due to the diatropic ring current of the COT core. Discussion of their structural analysis in solution and in the solid state is described. The work described in Chapter 4 focused on the synthesis of giant 3D discrete supramolecular architectures, with tuned dimensions, geometry and varied number of porphyrin units, obtained by simple mixing different (metallo)porphyrin modules. By appropriate tailoring of the meso-4’pyridylporphyrin connectors, i.e. increasing the number of basic donor sites and/or playing on their relative disposition, larger molecular architectures become easily available. Cleverly designed molecular building units, in terms of lability/inertness and hard/soft metal-to-ligand discriminations, quantitatively self-connect by formation of mutual coordination bonds. The obtained discrete multi-porphyrin structures constitute a spatially-ordered lattice of chromophores featuring photoinduced antenna-effect and charge transfer processes. Pursuing a modular synthetic approach, a library of fascinating In Chapter 5, Is reported the work performed during a six-month internship in the laboratories of Dr. Romain Ruppert, University of Strasbourg (FR), is devoted at investigating and tackling the possibility to employ a PdII-linked Zn(II)-porphyrin dimer (ZnPdZn), as alternative photo-active platforms for the assembling of discrete supramolecular sandwich structures.

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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEn-CNEN/SP

The present PhD thesis, entitled "Use of silica supports for enhancing the stability of folates and developing antimicrobial agents", focuses on the development and evaluation of new smart systems based on the use of silica nano- and microparticles as inorganic supports for the encapsulation or immobilization of two compounds types of interest to the food industry: vitamins and antimicrobials. The first chapter shows the effect of encapsulation of folic acid and 5-formyltetrahydrofolate in mesoporous silica microparticles functionalized with polyamines on the bioaccessibility and stability of both vitamers. The use of this hybrid organic-inorganic support allows the modification of the delivery of the vitamin dependent on the pH of the medium (inhibition of the release at an acidic pH, e.g. stomach, controlled release at a neutral pH, e.g. intestine) in in vitro systems. Also, the mesoporous support can protect the vitamin against degradation after exposure to external agents, such as pH, temperature or light. Furthermore, the incorporation of encapsulated folic acid into fruit juices (apple and orange) allowed us to study the modulating and protective capability of the delivery system in a real food matrix. This study has demonstrated that the amine-functionalized support is able to not only maintain folic acid inside pores after its incorporation into juices and to properly modify the delivery of the vitamin after simulated in vitro digestion, but to also protect the vitamin after the simulating the processing and storage of juices. The second chapter describes development of different antimicrobial agents based on the combination of organic active compounds with diverse silica materials. To this end, two different methodologies were used: encapsulation of the antimicrobial agent in the pores of mesoporous silica particles, and immobilization of the active compound on the surface of silica particles. The effect of encapsulation on the enhancement of the antimicrobial properties of a compound was studied by evaluating the antimicrobial activity of free and MCM-41 nanoparticles encapsulated caprylic acid against diverse pathogen food-borne bacteria. The results of the in vitro bacterial susceptibility assays and the determination of cellular damage by microscopy showed that the nanodevice maintains antimicrobial properties in relation to the free caprylic acid. The effect of the immobilization of an active compound on the surface of a support on the improvement of its antimicrobial properties was studied with two types of different molecules: polyamines (used as a molecular gate in the folates delivery system) and essential oils. In both cases, immobilization of the bioactive compound increased the antimicrobial effect of free molecules between 1- and 100-fold in the in vitro assays and in real food systems (fruit juices and pasteurized milk), in which immobilized compounds had a bacteriostatic effect during storage, while the equivalent free compound concentrations allowed microbial growth. In summary, it is concluded that the present thesis has evaluated the versatility of silicon oxide particles to solve two of the biggest problems in the food industry: alteration of active compounds during food processing and current antimicrobial systems losing of efficacy. Thus the developed devices may be used as alternative methods to traditional encapsulation systems or traditional food safety treatments.
La presente tesis doctoral que lleva por título "Uso de soportes de sílice para la mejora de la estabilidad de los folatos y el desarrollo de agentes antimicrobianos", se centra en el desarrollo y evaluación de nuevos sistemas inteligentes basados en el uso de nano- y micropartículas de sílice como soporte inorgánico para la encapsulación o inmovilización de dos tipos de compuestos de interés para la industria alimentaria: vitaminas y antimicrobianos. El primer capítulo muestra el efecto de la encapsulación de ácido fólico y 5-formiltretahidrofolato en micropartículas mesoporosas de sílice funcionalizadas con poliaminas sobre la bioaccessibilidad y estabilidad de ambos vitámeros. Por una parte, el uso de este soporte híbrido orgánico-inorgánico permite modular la liberación de la vitamina en función del pH del medio (inhibición de la liberación a pH ácido -estómago- y liberación controlada a pH neutro -intestino-) en sistemas in vitro. Así mismo, el soporte mesoporoso es capaz de proteger a la vitamina frente a la degradación tras la exposición a diversos agentes externos, como el pH, la temperatura o la luz. Además, la incorporación de ácido fólico encapsulado a zumos de frutas (manzana y naranja) ha permitido estudiar la capacidad moduladora y protectora del sistema de liberación en una matriz alimentaria real. Este estudio ha demostrado que el soporte funcionalizado con poliaminas no sólo es capaz de mantener el ácido fólico en el interior de los poros tras la incorporación a los zumos y modular correctamente la liberación del mismo tras la simulación de una digestión in vitro, sino que también es capaz de proteger la vitamina tras la simulación del procesado y almacenamiento de los zumos. En el segundo capítulo se describe el desarrollo de diferentes agentes antimicrobianos, basados en la combinación de compuestos activos orgánicos con diversos materiales de sílice. Para ello, se emplearon dos metodologías diferentes: la encapsulación del agente antimicrobiano en los poros de las partículas mesoporosas de sílice, y la inmovilización del compuesto activo sobre la superficie de las partículas de sílice. El efecto de la encapsulación sobre la mejora de las propiedades antimicrobianas de un compuesto se estudió determinando la actividad antimicrobiana de ácido caprílico libre y encapsulado en nanopartículas mesoporosas tipo MCM-41 frente a diversas bacterias patógenas presentes en alimentos. Los resultados de los ensayos in vitro de susceptibilidad bacteriana y la determinación del daño celular mediante microscopia mostraron que el nanodispositivo mantiene las propiedades antimicrobianas respecto al ácido caprílico libre. El efecto de la inmovilización de un compuesto activo sobre la superficie de un soporte en la mejora de sus propiedades antimicrobianas se estudió con dos tipos de moléculas diferentes: poliaminas (usadas como puerta molecular en el sistema de liberación de folatos) y aceites esenciales. En ambos casos la inmovilización del compuesto bioactivo incrementó entre 1-100 veces el poder antimicrobiano de las moléculas libres tanto en ensayos in vitro, como en ensayos en alimentos reales (zumos de frutas y leche pasteurizada) donde se comprobó que los compuestos inmovilizados tienen un efecto bacteriostático a lo largo del período de almacenamiento mientras que concentraciones equivalentes de compuesto libre permiten el crecimiento del microorganismo. En resumen, se puede concluir que en la presente tesis se ha evaluado la versatilidad de los sólidos de óxido de silicio para solventar dos de los grandes problemas de la industria alimentaria: alteración de compuestos bioactivos durante el procesado del alimento y la pérdida de la eficacia de los sistemas antimicrobianos actuales. Así, los dispositivos desarrollados podrían ser usados como métodos alternativos a los sistemas tradicionales de encapsulación o los tratamientos tradiciona
La present tesi doctoral, que porta per títol "Ús de suports de sílice per a la millora de l'estabilitat dels folats i el desenvolupament d'agents antimicrobians", es centra en el desenvolupament i avaluació de nous sistemes intel·ligents basats en l'ús de nano- i micropartícules de sílice com a suport inorgànic per a l'encapsulació o immobilització de dos tipus de compostos d'interès per a la indústria alimentària: vitamines i antimicrobians. El primer capítol mostra l'efecte de l'encapsulació d'àcid fòlic i 5-formiltretahidrofolat en micropartícules mesoporoses de sílice funcionalitzades amb poliamines sobre la bioaccessibilitat i estabilitat d'ambdós vitàmers. D'una banda, l'ús d'aquest suport híbrid orgànic-inorgànic permet modular l'alliberament de la vitamina en funció del pH del medi (inhibició de l'alliberament a pH àcid -estómac- i alliberament controlat a pH neutre -intestí-) en sistemes in vitro. Així mateix, el suport mesoporós és capaç de protegir a la vitamina enfront de la degradació després de l'exposició a diversos agents externs, com el pH, la temperatura o la llum. A més, la incorporació d'àcid fòlic encapsulat a sucs de fruites (poma i taronja) ha permès estudiar la capacitat moduladora i protectora del sistema d'alliberament en una matriu alimentària real. Aquest estudi ha demostrat que el suport funcionalitzat amb poliamines no sols és capaç de mantindre l'àcid fòlic a l'interior dels porus després de la incorporació als sucs i modular correctament l'alliberament del mateix després de la simulació d'una digestió in vitro, sinó que també és capaç de protegir la vitamina després de la simulació del processat i emmagatzemament dels sucs. En el segon capítol es descriu el desenvolupament de diferents agents antimicrobians, basats en la combinació de compostos actius orgànics amb diversos materials de sílice. Per a això, es van emprar dues metodologies diferents: l'encapsulació de l'agent antimicrobià en els porus de les partícules mesoporoses de sílice, i la immobilització del compost actiu sobre la superfície de les partícules de sílice. L'efecte de l'encapsulació sobre la millora de les propietats antimicrobianes d'un compost es va estudiar determinant l'activitat antimicrobiana d'àcid caprílic lliure i encapsulat en nanopartícules mesoporoses tipus MCM-41 enfront de diversos bacteris patògens presents en aliments. Els resultats dels assajos in vitro de susceptibilitat bacteriana i la determinació del dany cel·lular per mitjà de microscòpia van mostrar que el nanodispositiu manté les propietats antimicrobianes respecte a l'àcid caprílic lliure. L'efecte de la immobilització d'un compost actiu sobre la superfície d'un suport en la millora de les seues propietats antimicrobianes es va estudiar amb dues tipus de molècules diferents: poliamines (usades com a porta molecular en el sistema d'alliberament de folats) i olis essencials. En ambdós casos la immobilització del compost bioactiu va incrementar entre 1-100 vegades el poder antimicrobià de les molècules lliures tant en assajos in vitro, como en assajos en aliments reals (sucs de fruites i llet pasteuritzada) on es va comprovar que els compostos immobilitzats tenen un efecte bacteriostàtic al llarg del període d' emmagatzemament mentre que concentracions equivalents de compost lliure permeten el creixement del microorganisme. En resum, es pot concloure que en la present tesi s'ha avaluat la versatilitat dels sòlids d'òxid de silici per a resoldre dos dels grans problemes de la indústria alimentària: alteració de compostos bioactius durant el processat de l'aliment i la pèrdua de la eficàcia dels sistemes antimicrobians actuals. Així, els dispositius desenvolupats podrien ser usats com a mètodes alternatius als sistemes tradicionals d'encapsulació o els tractaments tradicionals per assegurar la innocuïtat dels aliments.
Ruiz Rico, M. (2016). Use of silica supports for enhancing the stability of folates and developing antimicrobial agents [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/76805
TESIS

[ES] La presente tesis doctoral, titulada "Microportadores inteligentes para la liberación controlada de sustancias de interés nutracéutico", se centra en el diseño y evaluación de sistemas híbridos orgánico-inorgánicos para proteger y liberar controladamente compuestos bioactivos. Dichos sistemas están basados en (i) materiales de sílice, principalmente partículas mesoporosas, como soporte inorgánico para almacenar y proteger la carga bioactiva; y (ii) una capa externa de biomoléculas como puerta molecular, que regula la liberación de la carga ante ciertos estímulos. En el primer capítulo de la tesis se describe el ácido oleico como puerta molecular. Este capítulo se subdivide en tres artículos diferentes, con distintos objetivos. En el primer artículo se emplea por primera vez el ácido oleico como puerta molecular de un soporte mesoporoso, cargado con la molécula modelo rodamina B. El material preparado es capaz de proteger la carga en las condiciones presentes en la boca y en el estómago, e inducir su liberación en el intestino con la acción surfactante de las sales biliares. El sistema se ha empleado para la liberación de vitamina B2, demostrando así la utilidad del diseño para la protección y liberación controlada de nutracéuticos. El segundo artículo evalúa la efectividad de esta puerta molecular en diferentes tipos de partículas mesoporosas de sílice, con diversos tamaños y estructuras de poro (MCM-41, MCM-48, SBA-15 y UVM-7). En todos los sistemas estudiados, la puerta molecular es capaz de mantener protegidas las moléculas cargadas, y liberarlas ante la presencia de sales biliares. El sólido basado en la estructura de UVM-7 se validó in vivo, observándose un retraso en la absorción intestinal de la rodamina gracias a su encapsulación. Por último, el tercer artículo incluido en este capítulo ha estudiado la posibilidad de incorporar puertas moleculares en filosilicatos. Se ha conseguido la protección y liberación controlada de biomoléculas de gran tamaño implicadas en el metabolismo humano (vitamina B12 y hematina) empleando filosilicatos funcionalizados con ácido oleico como puerta molecular. El segundo capítulo describe por primera vez el uso de la proteína zeína (prolamina de maíz) como puerta molecular. La presencia de la prolamina de maíz inhibe la salida de los compuestos antimicrobianos encapsulados (timol, carvacrol y cinamaldehído) liberándolos en presencia de las enzimas proteolíticas excretadas durante el crecimiento bacteriano. De todos los materiales desarrollados, el sistema cargado con cinamaldehído ha demostrado una inhibición del crecimiento de E. coli superior a la del compuesto libre. Finalmente, el tercer capítulo estudia la efectividad de la lactosa como puerta molecular para proteger aceites esenciales y liberarlos solo en las condiciones presentes en el intestino. Se han preparado tres materiales diferentes basados en MCM-41, cargados con timol, eugenol y cinamaldehído, y funcionalizados con lactosa para inhibir la salida de los compuestos. La acción enzimática de la lactasa secretada en el intestino es capaz de hidrolizar la puerta molecular en los correspondientes monosacáridos, liberando la carga a lo largo del lumen intestinal. Los microdispositivos diseñados han sido validados in vitro con células Caco-2, donde se ha observado el aumento de la capacidad citotóxica del cinamaldehído y la disminución de la permeabilidad a través del modelo de membrana intestinal gracias a su encapsulación. Finalmente, el microdispositivo cargado con cinamaldehído se ha validado in vivo ratificándose la disminución de la permeabilidad del compuesto y su mayor permanencia en el lumen intestinal. Así, la presente tesis doctoral ha demostrado la posibilidad de emplear biomoléculas sencillas de grado alimentario como puertas moleculares sobre diversos materiales de sílice. Estos nuevos sistemas han permitido proteger y liberar control
[CA] La present tesi doctoral, titulada "Microportadors intel·ligents per a l'alliberament controlat de substàncies d'interès nutracèutic", se centra en el disseny i avaluació de sistemes híbrids orgànic-inorgànics per a la protecció i alliberament controlat de compostos bioactius. Aquests sistemes estan basats en (i) materials de sílice, principalment partícules mesoporoses, com a suport inorgànic per emmagatzemar i protegir la càrrega bioactiva; i (ii) una capa externa de biomolècules com a porta molecular, que regula l'alliberament d'aquesta càrrega davant de determinats estímuls. En el primer capítol de la tesi es descriu l'àcid oleic com a porta molecular. Aquest capítol se subdivideix en tres articles diferents, amb objectius diferents. En el primer article s'empra per primera vegada l'àcid oleic com a porta molecular d'un suport mesoporós, carregat amb la molècula model rodamina B. El material preparat és capaç de protegir la càrrega en les condicions presents a la boca i a l'estómac, i induir el seu alliberament a l'intestí amb l'acció surfactant de les sals biliars. El sistema s'ha emprat per a l'alliberament de vitamina B2, demostrant així la utilitat del disseny per a la protecció i alliberament controlat de nutracèutics. El segon article avalua l'efectivitat d'aquesta porta molecular en diferents tipus de partícules mesoporoses de sílice, amb diverses mides i estructures de porus (MCM-41, MCM-48, SBA-15 i UVM-7). En tots els sistemes estudiats, la porta molecular és capaç de mantindre protegides les molècules carregades, i alliberar-les davant la presència de sals biliars. El sòlid basat en l'estructura de UVM-7 es validà in vivo, observant-se un retard en l'absorció intestinal de la rodamina gràcies a la seua encapsulació. Finalment, en el tercer article inclòs en aquest capítol s'ha estudiat la possibilitat d'incorporar portes moleculars en fil·losilicats. S'ha aconseguit la protecció i alliberament controlat de biomolècules de grans dimensions implicades en el metabolisme humà (vitamina B12 i hematina) emprant fil·losilicats funcionalitzats amb àcid oleic com a porta molecular. El segon capítol descriu per primera vegada l'ús de la proteïna zeïna (prolamina de dacsa) com a porta molecular. La presència de la prolamina de dacsa inhibeix la sortida dels compostos antimicrobians encapsulats (timol, carvacrol i cinamaldèhid) alliberant-los en presència dels enzims proteolítics excretades durant el creixement bacterià. De tots els materials desenvolupats, el sistema carregat amb cinamaldèhid ha demostrat una inhibició de l'creixement d'E. coli superior a la del compost lliure. Finalment, el tercer capítol estudia l'efectivitat de la lactosa com a porta molecular per protegir olis essencials i alliberar-los només en les condicions presents a l'intestí. S'han preparat tres materials diferents basats en MCM-41, carregats amb timol, eugenol i cinamaldèhid, i funcionalitzats amb lactosa per inhibir l'eixida dels compostos. L'acció enzimàtica de la lactasa secretada a l'intestí és capaç d'hidrolitzar la porta molecular en els corresponents monosacàrids, alliberant la càrrega al llarg del lumen intestinal. Els microdispositius dissenyats s'han validat in vitro amb cèl·lules Caco-2, on s'observà l'augment de la capacitat citotòxica del cinamaldèhid i la disminució de la permeabilitat a través del model de membrana intestinal gràcies a la seua encapsulació. Finalment, el microdispositiu carregat amb cinamaldèhid s'ha validat in vivo ratificant la disminució de la permeabilitat del compost i la seua major permanència al lumen intestinal. Així, la present tesi doctoral ha demostrat la possibilitat d'emprar biomolècules senzilles de grau alimentari com portes moleculars sobre diversos materials de sílice. Aquests nous sistemes han permès protegir i alliberar controladament diferents nutracèutics, millorant així la seua biodisponibilitat.
[EN] This PhD thesis, entitled "Smart microdevices for nutraceutical-delivery", is focused on the design and evaluation of organic-inorganic hybrid systems for the protection and controlled release of bioactive molecules. These systems are based on (i) silica materials, mainly mesoporous particles, as inorganic support to store and protect the bioactive cargo; and (ii) an outer layer of biomolecules that regulate the payload release triggered by certain stimuli. In the first chapter of the thesis oleic acid is described as a molecular gate. This chapter is subdivided into three different articles, with different objectives. In the first article, oleic acid is used for the first time as molecular gate of a mesoporous support, loaded with the rhodamine B model molecule. The designed material is capable of protecting the cargo under the conditions present in the mouth and stomach, and inducing its release in the small intestine with the surfactant action of bile salts. The system has been used for the release of vitamin B2, thus demonstrating the validity of the design for the protection and controlled release of nutraceuticals. The second article evaluates the effectiveness of this molecular gate in different types of mesoporous silica particles, with different sizes and pore structures (MCM-41, MCM-48, SBA-15 and UVM-7). In all the systems studied, the molecular gate is capable of keeping cargo molecules protected and releasing them in the presence of bile salts. The solid based on the structure of UVM-7 was validated in vivo, observing a delay in the intestinal absorption of rhodamine thanks to its encapsulation. Lastly, the third article included in this chapter has studied the possibility of incorporating molecular gates onto phyllosilicates. The protection and controlled release of large biomolecules involved in human metabolism (vitamin B12 and hematin) have been achieved using phyllosilicates functionalized with oleic acid as molecular gate. The second chapter describes for the first time the use of the protein zein (corn prolamine) as a molecular gate. The presence of corn prolamine inhibits the release of encapsulated antimicrobial compounds (thymol, carvacrol and cinnamaldehyde) releasing them in the presence of the proteolytic enzymes excreted during bacterial growth. Among all the materials developed, the cinnamaldehyde-loaded system has shown greater inhibition of E. coli growth than the free compound. Finally, the third chapter studies the effectiveness of lactose as a molecular gate to protect essential oils and release them only under the conditions present in the intestine. Three different materials based on MCM-41 loaded with thymol, eugenol, and cinnamaldehyde, and functionalized with lactose to inhibit the release of the compounds have been prepared. The enzymatic action of the lactase secreted in the intestine is capable of hydrolyzing the molecular gate into the corresponding monosaccharides, thus releasing the cargo along the intestinal lumen. The designed microdevices have been validated in vitro with Caco-2 cells, where an increase in the cytotoxic capacity of cinnamaldehyde and a decrease in permeability through the intestinal membrane model have been observed thanks to its encapsulation. Finally, the cinnamaldehyde-loaded microdevice has been validated in vivo, confirming the decrease in the permeability of the compound and its greater permanence in the intestinal lumen. Thus, the present PhD thesis has demonstrated the possibility of using simple food-grade biomolecules as gatekeepers on various silica materials. These new systems have allowed the protection and controlled release of different nutraceuticals, thus improving their bioavailability.
The authors also thank the Electron Microscopy Service at the UPV for support. The authors also thank Prof. Pedro Amorós for his explanations and guidance on the knowledge of phyllosilicates.
Poyatos Racionero, E. (2020). Smart microdevices for nutraceutical-controlled delivery [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/159247
TESIS

The inorganic components comprise 15% to 50% of the mass of atmospheric aerosols and, these along with the relative humidity, control the aerosol water content. For about the past 10 years the mass of the inorganic components of atmospheric aerosol was predicted assuming thermodynamic equilibrium between the volatile aerosol-phase inorganic species, NH₄NO₃ and NH₄Cl, and their gas-phase counterparts, NH₃, HNO₃, and HCl. In this thesis I examine this assumption and prove that 1) the time scales for equilibration between the gas and aerosol phases are often too long for equilibrium to hold, and 2) even when equilibrium holds, transport considerations often govern the size distribution of these aerosol components.

Water can comprise a significant portion of atmospheric aerosols under conditions of high relative humidity, whereas under conditions of sufficiently low relative humidity atmospheric aerosols tend to be dry. The deliquescence point is the relative humidity where the aerosol goes from a solid dry phase to an aqueous or mixed solid-aqueous phase. Previous to this thesis little had been known about the temperature and composition dependence of the deliquescence point. In this thesis I first derive an expression for the temperature dependence of the deliquescence point and then prove that in multicomponent solutions the deliquescence point is lower than in the deliquescence point of the individual single component solutions.

These theories of the transport, thermodynamic, and deliquescent properties of atmospheric aerosols are integrated into an aerosol inorganics model, AIM. The equilibrium predictions of AIM compare well to fundamental thermodynamic measurements. Comparison of the prediction of AIM to those of other aerosol equilibrium models show substantial disagreement in the predicted water content at lower relative humidities. The difference is due to the improved treatment of the deliquescence properties of mixed solute aerosols that is contained in AIM.

In the summer and fall of 1987 the California Air Resources Board conducted the Southern California Air Quality Study, SCAQS. During this study the atmospheric aerosols were measured at nine sites in the Los Angeles air basin. The measurements determined the size and composition distributions of the components of the aerosol and the concentrations of their gas phase counterparts during a series of intensive study periods. The comparison of these SCAQS measurements to the predictions of AIM have so much scatter that a departure from equilibrium, that can be attributed to transport limitations, cannot be discerned. When the measured size distributions are compared as another indication of transport-limited departure from equilibrium, we find that different size aerosol particles are not in mutual equilibrium. Although the SCAQS data do not indicate a transport-limited departure from equilibrium, they do support our hypothesis that transport considerations are essential to predicting the size distribution of the volatile inorganic species.

D. Tech. Chemistry.
Suggests an alternative methodology based on slurry sampling in the FF atomiser (Katskov, 2007) and simultaneous multi-element electrothermal (SMET) AAS determination using a low resolution CCD spectrometer linked to a continuum light source (Katskov and Khanye, 2010).

碩士
嘉南藥理科技大學
環境工程與科學系碩士班
93
The water-soluble inorganic composition and low-molecular-weight dicarboxylic acids of PM2.5 (fine particle) and PM2.5-10 (coarse particle) in both daytime and nighttime were evaluated during both non-episodic period of 19 September to 20 October, 2004 and episode of 26-30 November, 2004. During both non-episodic and episodic periods, the size distribution of the water-soluble inorganic salts / dicarboxylic acids was studied, including those in the nanoaerosols of 5-100 nm. To avoid the artifacts during each sampling period, the PM2.5 aerosol sampling was carried out after the gaseous pollutants were absorbed by annular denuder system (ADS). PM2.5 Aerosols collected on the Teflon filter (the first plate), but a part of PM2.5 NO3- was lost on the first filter. The lost NO3- species in PM2.5 aerosol was captured on the Nylon filter (the second plate) and was complete collected on the quartz filter of coating absorbent (the third plate). The percentage of PM2.5 NO3-on both Nylon and quartz filters displayed 10-13 % pf total aerosol NO3-. The percentage of total dicarboxylic acids in aerosol on both Nylon and quartz filters displayed 4.8-22.9 % of total dicarboxylic acids in aerosol. During both episodic and non-episodic periods, the concentration of SO42- in both daytime and nighttime always exceeded contents of NO3- and NH4+ within both fine and coarse fractions. However, the increase of NO3-, presenting the traffic emission, was significant during the period of episode. The percentage contribution of dicarboxylic acids in both PM2.5 and PM10 was 0.8-1.0 % by mass. Oxalic acid was the biggest single dicarboxylic acids. It was followed by succinic acids and malonic acid. When the alkaline situation occurred, the existence of NH4+ induced the alkenes (malic acid and maleic acid) to be more stable. During the episode, the transformation percentage of dicarboxylic acids in both PM2.5 and PM10 increased significantly. The percent of oxalic acid in measured dicarboxylic acids raised from 69 % during non-episode to be 73-80 % during episode, indicating the more carbon-bonding dicarboxylic acids decomposed to be 2 carbon-bonding products, oxalic acid during the period of episode. The dominant particle sizes of various inorganic salts including Na+, NH4+, K+, Mg2+, Ca2+, Cl-, NO3- and SO42- in aerosol appeared in both the droplet mode at 0.56-2.5 �慆 and the coarse mode at 3.1-6.2 �慆, respectively, during the non-episodic period. A small concentration peak of Aerosol NH4+ and SO42- appeared in the nuclei mode at 5-100 nm. Meanwhile, during the episode a significant concentration peak of various inorganic salts in aerosol increased in the nuclei mode at 5-100 nm. On the other hand, the concentration peak of low-molecular-weight dicarboxylic acids in aerosol appeared in both the droplet mode and the nuclei mode during the non-episodic period, but the significant concentration peak of dicarboxylic acids in aerosol existed in the nuclei mode, even at 5-18 nm, during the episode, indicating the concentration of primary dicarboxylic acids in aerosol has formatted more during the episode.

Management-induced degradation of soil chemical and microbial quality is one of the most pressing concerns and a considerable threat to the sustainability of agroecosystems. However, information on this important issue is limited and largely based on short-term studies. A long-term experiment initiated in 1939 at the University of Pretoria provided a unique opportunity to assess the direct and residual effects of manure and inorganic fertilizers on soil chemical properties, microbial components and maize yield in rotation with field pea. Long-term addition of manure resulted in increased total organic C (TOC), total N and available P levels in the soil. Seasonally, these nutrients exhibited variations that appeared to be related to influences of crop rotation. Soil N content in an adjacent native site remained relatively constant but tended to increase in the control and manured plots. Soil microbial biomass C, N and P and microbial populations were affected by previous manure application as well as by crop rotation. Microbial biomass and numbers were generally higher in the manured plots. Manure application also had substantial residual effects and resulted in maize grain yields higher than in the control. Long-term NPK application resulted in decreased TOC and basic cation contents, and lowering of soil pH. The decrease in TOC was greater in single fertilizer treatments whereas basic cation contents and pH declined more in the balanced fertilizer treatments. Soil microbial biomass and numbers were influenced by, and exhibited qualitative changes in response to, long-term fertilization. Crop rotation also exerted effects on chemical and microbial properties of the soil. Maize grain yield showed significant increases in response to balanced fertilizer treatments. Response of maize to simple fertilizer applications was not beneficial in terms of yield returns. These results suggest that judicious use of inorganic fertilizers may, in the long-term, maintain soil quality and productive capacity. A comparison of the effects of residual manure and NPK fertilizers on the content of selected nutrients, microbial properties, C and N inputs, tissue nutrient concentration and crop yield showed differences due to treatments. TOC, total N and available P levels were increased due to residual manure alone or in combination with NPK fertilizers. C and N inputs and tissue P concentration were also generally higher in manured than in the NPK treatment. However, the higher increase in nutrient contents of manured plots was not reflected in microbial properties of the soil. Despite lower nutrient levels, the NPK treatment resulted in relatively greater increases in microbial properties of the soil. The differential responses were largely due to differences in quality and decomposability of organic material. Organic material in the NPK treatment appeared to have a higher decomposition and turnover rate than in other treatments, suggesting that C limitation in soils of low C but good nutrient supply may be compensated by high turnover rates of the available organic materials. The beneficial effect of residual manure on microbial properties and crop yield was decreased by application of supplemental N fertilizer but remained unaffected by application of supplemental K fertilizer. The depressive effect of excess soil P levels on soil microbial properties and crop yield was exacerbated by supplemental N fertilizer and mitigated by supplemental manure and K fertilizer applied to residual P. The decrease in available P levels due to supplemental K application implies that this may serve as a viable alternative to ameliorate soils with excess P levels.
Thesis (PhD (Plant Production and Soil Science))--University of Pretoria, 2003.
Plant Production and Soil Science
unrestricted

Management-induced degradation of soil chemical and microbial quality is one of the most pressing concerns and a considerable threat to the sustainability of agroecosystems. However, information on this important issue is limited and largely based on short-term studies. A long-term experiment initiated in 1939 at the University of Pretoria provided a unique opportunity to assess the direct and residual effects of manure and inorganic fertilizers on soil chemical properties, microbial components and maize yield in rotation with field pea. Long-term addition of manure resulted in increased total organic C (TO C), total Nand available P levels in the soil. Seasonally, these nutrients exhibited variations that appeared to be related to influences of crop rotation. Soil N content in an adjacent native site remained relatively constant but tended to increase in the control and manured plots. Soil microbial biomass C, Nand P and microbial populations were affected by previous manure application as well as by crop rotation. Microbial biomass and numbers were generally higher in the manured plots. Manure application also had substantial residual effects and resulted in maize grain yields higher than in the control. Long-term NPK application resulted in decreased TOC and basic cation contents, and lowering of soil pH. The decrease in TOC was greater in single fertilizer treatments whereas basic cation contents and pH declined more in the balanced fertilizer treatments. Soil microbial biomass and numbers were influenced by, and exhibited qualitative changes in response to, long-term fertilization. Crop rotation also exerted effects on chemical and microbial properties of the soil. Maize grain yield showed significant increases in response to balanced fertilizer treatments. Response of maize to simple fertilizer applications was not beneficial in terms of yield returns. These results suggest that judicious use of inorganic fertilizers may, in the long-term, maintain soil quality and productive capacity. A comparison of the effects of residual manure and NPK fertilizers on the content of selected nutrients, microbial properties, C and N inputs, tissue nutrient concentration and crop yield showed differences due to treatments. TOC, total N and available P levels were increased due to residual manure alone or in combination with NPK fertilizers. C and N inputs and tissue P concentration were also generally higher in manured than in the NPK treatment. However, the higher increase in nutrient contents of manured plots was not reflected in microbial properties of the soil. Despite lower nutrient levels, the NPK treatment resulted in relatively greater increases in microbial properties of the soil. The differential responses were largely due to differences in quality and decomposability of organic material. Organic material in the NPK treatment appeared to have a higher decomposition and turnover rate than in other treatments, suggesting that C limitation in soils of low C but good nutrient supply may be compensated by high turnover rates of the available organic materials. The beneficial effect of residual manure on microbial properties and crop yield was decreased by application of supplemental N fertilizer but remained unaffected by application of supplemental K fertilizer. The depressive effect of excess soil P levels on soil microbial properties and crop yield was exacerbated by supplemental N fertilizer and mitigated by supplemental manure and K fertilizer applied to residual P. The decrease in available P levels due to supplemental K application implies that this may serve as a viable alternative to ameliorate soils with excess P levels.
Thesis (PhD)--University of Pretoria, 2010.
Plant Production and Soil Science
unrestricted

碩士
中原大學
化學工程研究所
92
In this study, two kinds of organic/inorganic hybrid membrane was prepared by adding montmorillonite (MMT) clay or 3-glycidoxypropyl -trimethoxysilane (GPTMS) in the chitosan solution. The effects of the condition of hybrid procedure and inorganic material content on the pervaporation performance and long-term stability of the hybrid membrane for the separation of aqueous isopropanol solution were investigated. The improvement of the mechanical and pervaporation properties of the organic/inorganic hybrid membranes are presumably due to the effect of nanoscale structure and the interaction between polymer and inorganic material. This study was divided into two parts according to starting materials and processing techniques. For the first part, chitosan/clay hybrid membranes were prepared by dispersing the nanolayers of inorganic montmorillonite (MMT) clay into organic chitosan matrix via the solution intercalation. The prepared hybrid membranes were characterized by using wide-angle X-ray diffraction (WXRD), transmission electron microscopy (TEM). Compared with pure chitosan membrane, the chitosan/clay hybrid membrane effectively improve the mechanical properties and thermal stability. In addition, the effects of the feed isopropanol concentration and the compositions of the chitosan/clay hybrid membranes on the pervaporation performances were also investigated. It was observed that the flux increased and the water concentration in permeate was not evidently affected with decreasing. the chitosan/clay hybrid membranes thickness. As the thickness of chitosan/ clay hybrid membranes was 8.5 μm, a flux of 640 g/m2 h, and water concentration in permeate higher than 99 wt% obtained with a 90 wt% aqueous isopropanol solution. Till now, the membrane life through the durability test for 90 wt% aqueous isopropanol solution has more than 453 days. For the second part, chitosan/silica membranes were prepared by sol-gel method. In order to confirm the crosslinking reaction between chitosan and crosslinking agent containing siloxane (GPTMS), solid state-nuclear magnetic resonance spectrometer (Solid state-NMR), and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used to characterize the hybrid membranes. While with 50 wt% GPTMS in chitosan matrix, we found that the silica network spreads out like a hyper-branched cluster by using scanning electron microscopy-energy dispersive spectrometer (SEM-EDS) and transmission electron microscopy (TEM). In addition, the effects of the compositions of chitosan/silica membranes on the pervaporation separation performances of 70 wt% aqueous isopropanol solution was investigated. The chitosan/silica membranes effectively improve the pervaporation performance and the long-term stability for the separation of aqueous isopropanol solution. 誌謝

Ulva as an aquaculture crop and IMTA component species has received mixed results globally; success has been achieved in South Africa and Israel, whilst in Europe the results have been poor. This project aims to determine if Ulva lactuca is a suitable candidate as an inorganic extractive species component within marine IMTA systems in British Columbia. The inorganic extractive feasibility of U. lactuca was determined with combination of real time growth and nutrient uptake experiments, alongside a SWOT analysis and literature review to reveal the possible potentialities and pitfalls. U. lactuca was cultivated in 680 litre tanks in the effluent of Wolf Eels, Anarrhichthys ocellatus in a recirculation system at the Aquatics facility at the University of Victoria. Growth experiments of wild local U. lactuca strains attained summer growth of up to 17.43% specific daily growth rate, with winter growth of up to 4.26% specific daily growth rate. U. lactuca demonstrates a preference for Ammonia-N uptake over other forms of inorganic nitrogen and a reduced nutrient uptake capacity during dark periods. Nitrate uptake capacity up to 202µm N gDW-1 day-1 was exhibited. These figures display the excellent biological potential of local Ulva lactuca strains to act as an inorganic extractive. However currently, long term maintenance of the crop proved problematic with instability with growth rates and nutrient uptake capacity. Cultivation issues in combination with poor economic outlook will restrict the feasibility of this species to specific types of IMTA system. Beneficial steps towards the deployment of U. lactuca inorganic extractive components would include: (i) the identification of suitable sterile strains or employment of “germling” spore production, (ii) the use of a rotational, light weight, cage cultivation system, (iii) being farmed in combination with a dark period nutrient removal species, such as Chondrus crispus, (iv) being farmed in conjunction with in-situ algivorous species.
Graduate
0792