Synthesis of Polymeric Nanoparticles for biomedical delivery applications

Polymeric nanoparticles (PNPs) have attracted considerable interest over the last few years due to their unique properties and behaviors provided by their small size. Such materials could be used in a wide range of applications such as diagnostics and drug delivery. Advantages of PNPs include controlled release, protection of drug molecules and its specific targeting, with concomitant increasing of the therapeutic index. In this work, novel sucrose and cholic acid based PNPs were prepared from different polymers, namely polyethylene glycol (PEG), poly(D,L-lactic-co-glycolic acid) (PLGA) and PLGA-co-PEG copolymer. In these PNP carriers, cholic acid will act as a drug incorporation site and the carbohydrate as targeting moiety. The uptake of nanoparticles into cells usually involves endocytotic processes, which depend primarily on their size and surface characteristics. These properties can be tuned by the nanoparticle preparation method. Therefore, the nanoprecipitation and the emulsion-solvent evaporation method were applied to prepare the PNPs. The influence of various parameters, such as concentration of the starting solution, evaporation method and solvent properties on the nanoparticle size, size distribution and morphology were studied. The PNPs were characterized by using atomic force microscopy (AFM), scanning electron microscopy (SEM) and dynamic light scattering (DLS) to assess their size distribution and morphology. The PNPs obtained by nanoprecipitation ranged in size between 90 nm and 130 nm with a very low polydispersity index (PDI < 0.3). On the other hand, the PNPs produced by the emulsion-solvent evaporation method revealed particle sizes around 300 nm with a high PDI value. More detailed information was found in AFM and SEM images, which demonstrated that all these PNPs were regularly spherical. ζ-potential measurements were satisfactory and evidenced the importance of sucrose moiety on the polymeric system, which was responsible for the obtained negative surface charge, providing colloidal stability. The results of this study show that sucrose and cholic acid based polymeric conjugates can be successfully used to prepare PNPs with tunable physicochemical characteristics. In addition, it provides novel information about the materials used and the methods applied. It is hoped that this work will be useful for the development of novel carbohydrate based nanoparticles for biomedical applications, specifically for targeted drug delivery.

Reactive electron scattering from biomolecules and technologically relevant molecules

The role of a set of gases relevant within the context of biomolecules and technologically relevant molecules under the interaction of low-energy electrons was studied in an effort to contribute to the understanding of the underlying processes yielding negative ion formation. The results are relevant within the context of damage to living material exposed to energetic radiation, to the role of dopants in the ion-molecule chemistry processes, to Electron Beam Induced Deposition (EBID) and Ion Beam Induced Deposition (IBID) techniques. The research described in this thesis addresses dissociative electron attachment (DEA) and electron transfer studies involving experimental setups from the University of Innsbruck, Austria and Universidade Nova de Lisboa, Portugal, respectively. This thesis presents DEA studies, obtained by a double focusing mass spectrometer, of dimethyl disulphide (C2H6S2), two isomers, enflurane and isoflurane (C3F5Cl5) and two chlorinated ethanes, pentachloroethane (C2HCl5) and hexachloroethane (C2Cl6), along with quantum chemical calculations providing information on the molecular orbitals as well as thermochemical thresholds of anion formation for enflurane, isoflurane, pentachloroethane and hexachloroethane. The experiments represent the most accurate DEA studies to these molecules, with significant differences from previous work reported in the literature. As far as electron transfer studies are concerned, negative ion formation in collisions of neutral potassium atoms with N1 and N3 methylated pyrimidine molecules were obtained by time-of-flight mass spectrometry (TOF). The results obtained allowed to propose concerted mechanisms for site and bond selective excision of bonds.

How to bring equity investors to the social sector? A quasi-equity approach through the case study of SPEAK

As nonprofits do not have access to the same capital markets as for-profit enterprises, organizations usually scramble for funding to keep up with their mission. This scenario can be changed through the use of the right financial engineering. This Work Project aims at studying an innovative financing mechanism based on the concept of quasi-equity for organizations devoted to social ends to cope with their capital needs. A quasi-equity investment model is built for the Portuguese social business SPEAK, and an in-depth assessment of its current financial, organizational and impact situations is conducted. This is a pioneer case study in Portugal.

The effectiveness of a rotavirus vaccine in preventing hospitalizations and deaths presumably due to acute infectious diarrhea in Brazilian children: a quasi-experimental study

INTRODUCTION: Rotavirus is the main etiologic agent of acute infectious diarrhea in children worldwide. Considering that a rotavirus vaccine (G1P8, strain RIX4414) was added to the Brazilian vaccination schedule in 2006, we aimed to study its effectiveness and safety regarding intestinal intussusception. METHODS: A quasi-experimental trial was performed in which the primary outcome was the number of hospitalizations that were presumably due to acute infectious diarrhea per 100,000 children at risk (0-4 years old). The secondary outcomes included mortality due to acute infectious diarrhea and the intestinal intussusception rates in children in the same age range. We analyzed three scenarios: Health Division XIII of the State of São Paulo (DRS XIII) from 2002 to 2008, the State of São Paulo, and Brazil from 2002 to 2012. RESULTS: The averages of the hospitalization rates for 100,000 children in the pre- and post-vaccination periods were 1,413 and 959, respectively, for DRS XIII (RR=0.67), 312 and 249, respectively, for the State of São Paulo (RR=0.79), and 718 and 576, respectively, for Brazil (RR=0.8). The mortality rate per 100,000 children in the pre- and post-vaccination periods was 2.0 and 1.3, respectively, for DRS XIII (RR=0.66), 5.5 and 2.5, respectively, for the State of São Paulo (RR=0.47), and 15.0 and 8.0, respectively, for Brazil (RR=0.53). The average annual rates of intussusception for 100,000 children in DRS XIII were 28.0 and 22.0 (RR=0.77) in the pre- and post-vaccination periods, respectively. CONCLUSIONS: A monovalent rotavirus vaccine was demonstrated to be effective in preventing the hospitalizations and deaths of children that were presumably due to acute infectious diarrhea, without increasing the risk of intestinal intussusception.

A formação em rastreio e intervenções breves do álcool muda as atitudes dos profissionais de saúde ocupacional? : estudo quasi experimental exploratório para uma estratégia para o meio laboral

RESUMO - Estudos anteriores nos Cuidados de Saúde Primários (CSP) apontam para um incremento da Deteção Precoce (DP) e Intervenções Breves (IB) em pacientes com Problemas Ligados ao Álcool (PLA) após formação apropriada dos profissionais de saúde (com melhoria das suas atitudes). Este estudo quasi experimental, exploratório, é pioneiro no âmbito da Saúde Ocupacional (SO) para a implementação de Rastreio/DP e IB nos PLA. O objetivo principal foi avaliar se uma formação sobre Rastreio/DP e IB pode melhorar as atitudes dos profissionais de SO ao lidar com os PLA em Meio Laboral (PLAML). Foi aplicado um questionário em duas partes: Q1/pré-formação (variáveis sociodemográficas, profissionais, competências em alcoologia, experiência pessoal com álcool/familiares com PLA, dificuldades em lidar com trabalhadores com PLA, AUDIT-C e SAAPPQ) e Q2/pós-formação (avaliação da formação e das atitudes SAAPPQ - Adequação, Legitimidade, Motivação, Autoestima e Satisfação). Os resultados na amostra (N=39) revelaram um aumento sobretudo na Adequação e Satisfação. No entanto, naqueles com níveis baixos das atitudes pré-formação constou-se melhoria das atitudes à excepção da Autoestima e foram encontradas algumas associações com as características do perfil inicial dos participantes. Sugerem-se estudos posteriores para identificação de pacotes formativos mais efetivos e propostas para um Plano integrador de RIB para PLAML

Measurement of charged-particle spectra in Pb+Pb collisions at √sNN = 2.76TeV with the ATLAS detector at the LHC

Charged-particle spectra obtained in 0.15nb−1 of Pb+Pb interactions at sNN−−−√=2.76TeV and 4.2pb−1 of pp interactions at s√=2.76TeV with the ATLAS detector at the LHC are presented in a wide transverse momentum (0.5

Search for a Heavy Neutral Particle Decaying to eμ, eτ, or μτ in pp Collisions at s√=8 TeV with the ATLAS Detector

This Letter presents a search for a heavy neutral particle decaying into an opposite-sign different-flavor dilepton pair, e±μ∓, e±τ∓, or μ±τ∓ using 20.3 fb−1 of pp collision data at s√=8 TeV collected by the ATLAS detector at the LHC. The numbers of observed candidate events are compatible with the Standard Model expectations. Limits are set on the cross section of new phenomena in two scenarios: the production of ν~τ in R-parity-violating supersymmetric models and the production of a lepton-flavor-violating Z′ vector boson.

Electrically tunable resonant scattering in fluorinated bilayer graphene

Adatom-decorated graphene offers a promising new path towards spintronics in the ultrathin limit. We combine experiment and theory to investigate the electronic properties of dilutely fluorinated bilayer graphene, where the fluorine adatoms covalently bond to the top graphene layer. We show that fluorine adatoms give rise to resonant impurity states near the charge neutrality point of the bilayer, leading to strong scattering of charge carriers and hopping conduction inside a field-induced band gap. Remarkably, the application of an electric field across the layers is shown to tune the resonant scattering amplitude from fluorine adatoms by nearly twofold. The experimental observations are well explained by a theoretical analysis combining Boltzmann transport equations and fully quantum-mechanical methods. This paradigm can be generalized to many bilayer graphene-adatom materials, and we envision that the realization of electrically tunable resonance may be a key advantage in graphene-based spintronic devices.

Two-particle Bose–Einstein correlations in pp collisions at s√= 0.9 and 7 TeV measured with the ATLAS detector

The paper presents studies of Bose--Einstein Correlations (BEC) for pairs of like-sign charged particles measured in the kinematic range pT> 100 MeV and |η|< 2.5 in proton--proton collisions at centre-of-mass energies of 0.9 and 7 TeV with the ATLAS detector at the CERN Large Hadron Collider. The integrated luminosities are approximately 7 μb−1, 190 μb−1 and 12.4 nb−1 for 0.9 TeV, 7 TeV minimum-bias and 7 TeV high-multiplicity data samples, respectively. The multiplicity dependence of the BEC parameters characterizing the correlation strength and the correlation source size are investigated for charged-particle multiplicities of up to 240. A saturation effect in the multiplicity dependence of the correlation source size is observed using the high-multiplicity 7 TeV data sample. The dependence of the BEC parameters on the average transverse momentum of the particle pair is also investigated.

Green's relations, regularity and abundancy for semigroups of quasi-onto transformations

Let V be an infinite-dimensional vector space and for every infinite cardinal n such that n≤dimV, let AE(V,n) denote the semigroup of all linear transformations of V whose defect is less than n. In 2009, Mendes-Gonçalves and Sullivan studied the ideal structure of AE(V,n). Here, we consider a similarly-defined semigroup AE(X,q) of transformations defined on an infinite set X. Quite surprisingly, the results obtained for sets differ substantially from the results obtained in the linear setting.

In vitro digestion and stability assessment of b-lactoglobulin/riboflavin nanostructures

B-Lactoglobulin (b-Lg) is the major protein fraction of bovine whey serum and a primary gelling agent. b-Lg has a high nutritional value, is stable at low pH being highly resistant to proteolytic degradation in the stomach, besides, it has the ability of acting as an encapsulating agent. This study aims at assessing the ability of b-Lg nanostructures to associate a nutraceutical - i.e. riboflavin - and release it in a controlled manner throughout an in vitro gastrointestinal (GI) system. For this reason b-Lg nanostructures loaded with riboflavin were critically characterized in terms of their morphology (i.e. size, polydispersity, -potential and shape) by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and efficiency to associate to riboflavin through spectrofluorimetry. Furthermore, these nanocomplexes were evaluated in an in vitro GI model, simulating the physiological conditions. Stable b-Lg nanostructures were obtained at pH 6, of spherical shape, characterized by particle size of 172±1 nm, low polydispersity (i.e. PDI of 0.06±0.02), -potential of -32±3 mV and association efficiency (AE) of 26±1 %. b-Lg nanostructures showed to be stable upon their passage throughout stomach (i.e. particle size, PDI and potential of 248±10 nm, 0.18±0.03 and 18±3 mV, respectively). Concerning their passage throughout the intestine, such nanostructures were mostly degraded in the duodenum. Regarding riboflavin, a release of about 11 % was observed after their passage through stomach, while 35 %, 38 % and 5 % were the released percentages of the total riboflavin associated observed after passage through duodenum, jejunum and ileum, respectively. Hence,b-Lg nanostructures showed to be suitable carriers for riboflavin until the intestine, where their degradation occurs. b-Lg also showed to be structurally stable, under food simulant conditions (yoghurt simulant, composed of 3 % acetic acid), over 14 days, with a protective effect upon riboflavin activity, releasing it in a 7 day period.

In-line rheo-optical microstructural characterization of complex polymer systems

Tese de Doutoramento em Ciência e Engenharia de Polímeros e Compósitos.

Particle transport in fouling caused by kaolin-water suspensions on copper tubes

Particulate fouling tests were carried out using kaolin-water suspensions flowing through an annular heat exchanger with a copper inner tube. The flow rate was changed from test to test, but the fluid temperature and pH, as well as the particle concentration, were maintained constant. In the lower range of fluid velocities (<0.5 m/s), the deposition process seemed to be controlled by mass transfer. The corresponding experimental transport fluxes were compared to the predictions obtained with several models, showing that diffusion governed particle transport. The absolute values of the mass transfer fluxes and their dependences on the Reynolds number were satisfactorily predicted by some of the models.

Anwendung der Coupled-Cluster-Methode zur Untersuchung frustrierter quasi-eindimensionaler und zweidimensionaler Quantenspinsysteme

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2010