Développement d’une lentille cornéenne médicamentée

L’utilisation de lentilles cornéennes peut servir à améliorer le profil d’administration d’un principe actif dans les yeux. Avec une efficacité d’administration de 5% par l’utilisation de gouttes, on comprend rapidement que l’administration oculaire doit être améliorée. Cette faible administration a donné naissance à plusieurs tentatives visant à fabriquer des lentilles cornéennes médicamentées. Cependant, à cause de multiples raisons, aucune de ces tentatives n’a actuellement été mise sur le marché. Nous proposons dans cette étude, une possible amélioration des systèmes établis par le développement d’une lentille cornéenne à base de 2-(hydroxyéthyle)méthacrylate (HEMA), dans laquelle des microgels, à base de poly N-isopropylacrylamide (pNIPAM) thermosensible encapsulant un principe actif, seront incorporé. Nous avons donc débuté par développer une méthode analytique sensible par HPCL-MS/MS capable de quantifier plusieurs molécules à la fois. La méthode résultante a été validée selon les différents critères de la FDA et l’ICH en démontrant des limites de quantifications et de détections suffisamment basses, autant dans des fluides simulés que dans les tissus d’yeux de lapins. La méthode a été validée pour sept médicaments ophtalmiques : Pilocarpine, lidocaïne, proparacaïne, atropine, acétonide de triamcinolone, timolol et prednisolone. Nous avons ensuite fait la synthèse des microgels chargés négativement à base de NIPAM et d’acide méthacrylique (MAA). Nous avons encapsulé une molécule modèle dans des particules ayant une taille entre 200 et 600 nm dépendant de la composition ainsi qu’un potentiel zêta variant en fonction de la température. L’encapsulation de la rhodamine 6G (R6G) dans les microgels a été possible jusqu’à un chargement (DL%) de 38%. L’utilisation des isothermes de Langmuir a permis de montrer que l’encapsulation était principalement le résultat d’interactions électrostatiques entre les MAA et la R6G. Des cinétiques de libérations ont été effectuées à partir d’hydrogels d’acrylamide chargés en microgels encapsulant la R6G. Il a été trouvé que la libération des hydrogels chargés en microgels s’effectuait majoritairement selon l’affinité au microgel et sur une période d’environ 4-24 heures. La libération à partir de ces systèmes a été comparée à des formules d’hydrogels contenant des liposomes ou des nanogels de chitosan. Ces trois derniers (liposomes, microgels et nanogels) ont présenté des résultats prometteurs pour différentes applications avec différents profils de libérations. Enfin, nous avons transposé le modèle développé avec les gels d’acrylamide pour fabriquer des lentilles de contact de 260 à 340 µm d’épaisseur à base de pHEMA contenant les microgels avec une molécule encapsulée devant être administrée dans les yeux. Nous avons modifié la composition de l’hydrogel en incorporant un polymère linéaire, la polyvinylpyrrolidone (PVP). L’obtention d’hydrogels partiellement interpénétrés améliore la rétention d’eau dans les lentilles cornéennes. L’encapsulation dans les microgels chargés négativement a donné de meilleurs rendements avec la lidocaïne et cette dernière a été libérée de la lentille de pHEMA en totalité en approximativement 2 heures qu’elle soit ou non encapsulée dans des microgels. Ainsi dans cette étude pilote, l’impact des microgels n’a pas pu être déterminé et, de ce fait, nécessitera des études approfondies sur la structure et les propriétés de la lentille qui a été développée. En utilisant des modèles de libération plus représentatifs de la physiologie de l’œil, nous pourrions conclure avec plus de certitude concernant l’efficacité d’un tel système d’administration et s’il est possible de l’optimiser.

Isotopic ratios and concentrations for mineral-associated and particulate organic fractions of sediment core Wilson_Lake samples

The flux of sediment and organic carbon from continents to the coastal ocean is an important factor governing organic burial in coastal sediments, and these systems preserve important records of environmental and biogeochemical conditions during past global change events. Burial of organic materials in coastal systems can be promoted by chemical resilience or through protection by association with mineral surfaces, but the role and influence of these processes on organic records from ancient sediments is poorly known. We studied sediment and organic matter burial as particulate organic matter (POM) and mineral-bound organic matter (MOM) in near-shore marine sediments from the Wilson Lake core (New Jersey, USA) that span the Paleocene-Eocene thermal maximum (PETM), a climatic perturbation 55.9 Myr ago. Our results show that distinct POM and MOM fractions can be isolated from sediments. Both fractions appear to be dominated by terrestrial material, but POM consisted primarily of recently synthesized material whereas MOM included a significant fraction of pre-aged organic matter from soils or ancient sediments. Variation in organic burial through the PETM is associated with changes in inorganic nitrogen burial, clay mineralogy, and clastic grain size that we associate with enhanced continental weathering, erosion and redeposition of ancient kaolinites, and eustatic sea level variation, respectively. These results provide a new perspective on factors governing carbon burial and carbon isotope records in ancient marine margin settings and offer information on rate and phasing of late Paleocene/early Eocene Earth system changes that may constrain interpretations of the cause of the PETM climate change event.

Linking surficial geomorphology with vertical structure in high and low energy marine environments

Senior thesis written for Oceanography 445

Coalescence of secondary dispersions in packed beds

A study has been made of the coalescence of secondary dispersions in beds of monosized glass ballotini. The variables investigated were superficial velocity, bed depth, ballotini size and dispersed phase concentration. Equipment was designed to generate a toluene ln water dispersion with phase ratios from 0.1 - 1.0 v/v % and whose mean drop size was determined using a Coulter Counter. The coalesced drops were sized by photography and the mean diameter of the effluent drops was determined using a Malvern Particle Size Analyser. Previous models describing single phase flow in porous media are reviewed and it was found that the experimental data obtained in this study is best represented by the Carman-Kozeny equations. Relative permeability correlations were used to predict the saturation profiles across the bed from measured two phase pressure drop data. Theoretical comparison of drop capture mechanisms indicated that direct and indirect interception are predominant. The total capture efficiency for the bed can also be evaluated using Spielman and Fitzpatrick's correlation.The resulting equation is used to predict the initial, local drop capture rate in a coalescer. A mathematical description of the saturation profiles is formulated and verified by the saturation profiles obtained by relative permeability. Based on the Carman-Kozeny equation, an expression is derived analytically to .predict the two phase pressure drop using the parameters which characterise the saturation profiles. By specifying the local saturation at the inlet face for a given velocity and phase ratio, good agreement between experimental pressure drop data and the model predictions was obtained. An attempt to predict the exit drop size has been made using an analogy for flow through non cylindrical channels.

Having your day in court:judicial opportunity and tactical choice in Anti-GMO campaigns in France and the United Kingdom

Investigating the recent direct action campaigns against genetically modified crops in France and the United Kingdom, the authors set out to understand how contrasting judicial systems and cultures affect the way that activists choose to commit ostensibly illegal actions and how they negotiate the trade-offs between effectiveness and public accountability. The authors find evidence that prosecution outcomes across different judicial systems are consistent and relatively predictable and consequently argue that the concept of a “judicial opportunity structure” is useful for developing scholars’ understanding of social movement trajectories. The authors also find that these differential judicial opportunities cannot adequately account for the tactical choices made by activists with respect to the staging of covert or overt direct action; rather, explanations of tactical choice are better accounted for by movement ideas, cultures, and traditions.

Développement d’une lentille cornéenne médicamentée

L’utilisation de lentilles cornéennes peut servir à améliorer le profil d’administration d’un principe actif dans les yeux. Avec une efficacité d’administration de 5% par l’utilisation de gouttes, on comprend rapidement que l’administration oculaire doit être améliorée. Cette faible administration a donné naissance à plusieurs tentatives visant à fabriquer des lentilles cornéennes médicamentées. Cependant, à cause de multiples raisons, aucune de ces tentatives n’a actuellement été mise sur le marché. Nous proposons dans cette étude, une possible amélioration des systèmes établis par le développement d’une lentille cornéenne à base de 2-(hydroxyéthyle)méthacrylate (HEMA), dans laquelle des microgels, à base de poly N-isopropylacrylamide (pNIPAM) thermosensible encapsulant un principe actif, seront incorporé. Nous avons donc débuté par développer une méthode analytique sensible par HPCL-MS/MS capable de quantifier plusieurs molécules à la fois. La méthode résultante a été validée selon les différents critères de la FDA et l’ICH en démontrant des limites de quantifications et de détections suffisamment basses, autant dans des fluides simulés que dans les tissus d’yeux de lapins. La méthode a été validée pour sept médicaments ophtalmiques : Pilocarpine, lidocaïne, proparacaïne, atropine, acétonide de triamcinolone, timolol et prednisolone. Nous avons ensuite fait la synthèse des microgels chargés négativement à base de NIPAM et d’acide méthacrylique (MAA). Nous avons encapsulé une molécule modèle dans des particules ayant une taille entre 200 et 600 nm dépendant de la composition ainsi qu’un potentiel zêta variant en fonction de la température. L’encapsulation de la rhodamine 6G (R6G) dans les microgels a été possible jusqu’à un chargement (DL%) de 38%. L’utilisation des isothermes de Langmuir a permis de montrer que l’encapsulation était principalement le résultat d’interactions électrostatiques entre les MAA et la R6G. Des cinétiques de libérations ont été effectuées à partir d’hydrogels d’acrylamide chargés en microgels encapsulant la R6G. Il a été trouvé que la libération des hydrogels chargés en microgels s’effectuait majoritairement selon l’affinité au microgel et sur une période d’environ 4-24 heures. La libération à partir de ces systèmes a été comparée à des formules d’hydrogels contenant des liposomes ou des nanogels de chitosan. Ces trois derniers (liposomes, microgels et nanogels) ont présenté des résultats prometteurs pour différentes applications avec différents profils de libérations. Enfin, nous avons transposé le modèle développé avec les gels d’acrylamide pour fabriquer des lentilles de contact de 260 à 340 µm d’épaisseur à base de pHEMA contenant les microgels avec une molécule encapsulée devant être administrée dans les yeux. Nous avons modifié la composition de l’hydrogel en incorporant un polymère linéaire, la polyvinylpyrrolidone (PVP). L’obtention d’hydrogels partiellement interpénétrés améliore la rétention d’eau dans les lentilles cornéennes. L’encapsulation dans les microgels chargés négativement a donné de meilleurs rendements avec la lidocaïne et cette dernière a été libérée de la lentille de pHEMA en totalité en approximativement 2 heures qu’elle soit ou non encapsulée dans des microgels. Ainsi dans cette étude pilote, l’impact des microgels n’a pas pu être déterminé et, de ce fait, nécessitera des études approfondies sur la structure et les propriétés de la lentille qui a été développée. En utilisant des modèles de libération plus représentatifs de la physiologie de l’œil, nous pourrions conclure avec plus de certitude concernant l’efficacité d’un tel système d’administration et s’il est possible de l’optimiser.

Mineralogical (bulk rock and clay fraction) and stable isotope composition (d13C, d18O) of Aptian deposits of the Bir Oum Ali succession, central Tunisia

Alternations between siliciclastic, carbonate and evaporitic sedimentary systems, as recorded in the Aptian mixed succession of southern Tunisia, reflect profound palaeoceanographic and palaeoclimatic changes in this area of the southern Tethyan margin. The evolution from Urgonian-type carbonates (Berrani Formation, lower Aptian) at the base of the series, to intervals dominated by gypsum or detrital deposits in the remainder of the Aptian is thought to result from the interplay between climate change and tectonic activity that affected North Africa. Based on the evolution of clay mineral assemblages, the early Aptian is interpreted as having been dominated by slightly humid conditions, since smectitic minerals are observed. Near the early to late Aptian boundary, the onset of a gypsiferous sedimentation is associated with the appearance of palygorskite and sepiolite, which supports the installation of arid conditions in this area of the southern Tethyan margin. The evaporitic sedimentation may have also been promoted by the peculiar tectonic setting of the Bir Oum Ali area during the Aptian, where local subsidence may have been tectonically enhanced linked to the opening of northern and central Atlantic. Stress associated with the west and central African rift systems may have triggered the development of NW-SE, hemi-graben structures. Uplifted areas may have constituted potential new sources for clastic material that has been subsequently deposited during the late Aptian. Chemostratigraphic (d13C) correlation of the Bir Oum Ali succession with other peri-Tethyan regions complements biostratigraphic findings, and indicates that a potential expression of the Oceanic Anoxic Event (OAE) 1a may be preserved in this area of Tunisia. Although the characteristic negative spike at the base of this event is not recognized in the present study, a subsequent, large positive excursion with d13C values is of similar amplitude and absolute values to that reported from other peri-Tethyan regions, thus supporting the identification of isotopic segments C4-C7 of the OAE1a. The absence of the negative spike may be linked to either non preservation or non deposition: the OAE1a occurred in a global transgressive context, and since the Bir Oum Ali region was located in the innermost part of the southern Tethyan margin during most of the Aptian, stratigraphic hiatuses may have been longer than in other regions of the Tethys. This emphasizes the importance of integrating several stratigraphic disciplines (bio-, chemo- and sequence stratigraphy) when performing long-distance correlation.

Tectonic geomorphology assessment of the Ken River catchment near Panna, Madhya Pradesh, India

This thesis focuses on tectonic geomorphology and the response of the Ken River catchment to postulated tectonic forcing along a NE-striking monocline fold in the Panna region, Madhya Pradesh, India. Peninsular India is underlain by three northeast-trending paleotopographic ridges of Precambrian Indian basement, bounded by crustal-scale faults. Of particular interest is the Pokhara lineament, a crustal scale fault that defines the eastern edge of the Faizabad ridge, a paleotopographic high cored by the Archean Bundelkhand craton. The Pokhara lineament coincides with the monocline structure developed in the Proterozoic Vindhyan Supergroup rocks along the Bundelkhand cratonic margin. A peculiar, deeply incised meander-like feature, preserved along the Ken River where it flows through the monocline, may be intimately related to the tectonic regime of this system. This thesis examines 41 longitudinal stream profiles across the length of the monocline structure to identify any tectonic signals generated from recent surface uplift above the Pokhara lineament. It also investigates the evolution of the Ken River catchment in response to the generation of the monocline fold. Digital Elevation Models (DEM) from Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) were used to delineate a series of tributary watersheds and extract individual stream profiles which were imported into MATLAB for analysis. Regression limits were chosen to define distinct channel segments, and knickpoints were defined at breaks between channel segments where there was a discrete change in the steepness of the channel profile. The longitudinal channel profiles exhibit the characteristics of a fluvial system in transient state. There is a significant downstream increase in normalized steepness index in the channel profiles, as well as a general increase in concavity downstream, with some channels exhibiting convex, over-steepened segments. Normalized steepness indices and uppermost knickpoint elevations are on average much higher in streams along the southwest segment of the monocline compared to streams along the northeast segment. Most channel profiles have two to three knickpoints, predominantly exhibiting slope-break morphology. These data have important implications for recent surface uplift above the Pokhara lineament. Furthermore, geomorphic features preserved along the Ken River suggest that it is an antecedent river. The incised meander-like feature appears to be the abandoned river valley of a former Ken River course that was captured during the evolution of the landscape by what is the present day Ken River.

Rare earth elements and neodymium isotopes in world river sediments revisited

Over the past decades, rare earth elements (REE) and their radioactive isotopes have received tremendous attention in sedimentary geochemistry, as tracers for the geological history of the continental crust and provenance studies. In this study, we report on elemental concentrations and neodymium (Nd) isotopic compositions for a large number of sediments collected near the mouth of rivers worldwide, including some of the world’s major rivers. Sediments were leached for removal of non-detrital components, and both clay and silt fractions were retained for separate geochemical analyses. Our aim was to re-examine, at the scale of a large systematic survey, whether or not REE and Nd isotopes could be fractionated during Earth surface processes. Our results confirmed earlier assumptions that river sediments do not generally exhibit any significant grain-size dependent Nd isotopic variability. Most sediments from rivers draining old cratonic areas, sedimentary systems and volcanic provinces displayed similar Nd isotopic signatures in both clay and silt fractions, with ΔεNd (clay-silt) < |1.| A subtle decoupling of Nd isotopes between clays and silts was identified however in a few major river systems (e.g. Nile, Mississippi, Fraser), with clays being systematically shifted towards more radiogenic values. This observation suggests that preferential weathering of volcanic and/or sedimentary rocks relative to more resistant lithologies may occur in river basins, possibly leading locally to Nd isotopic decoupling between different size fractions. Except for volcanogenic sediments, silt fractions generally displayed homogeneous REE concentrations, exhibiting relatively flat shale-normalized patterns. However, clay fractions were almost systematically characterized by a progressive enrichment from the heavy to the light REE and a positive europium (Eu) anomaly. In agreement with results from previous soil investigations, the observed REE fractionation between clays and silts is probably best explained by preferential alteration of feldspars and/or accessory mineral phases. Importantly, this finding clearly indicates that silicate weathering can lead to decoupling of REE between different grain-size fractions, with implications for sediment provenance studies. Finally, we propose a set of values for a World River Average Clay (WRAC) and Average Silt (WRAS), which provide new estimates for the average composition of the weathered and eroded upper continental crust, respectively, and could be used for future comparison purposes.

“To be or not to be retained… Thats' the question!” Retention, self-esteem, self-concept, achievement goals, and grades

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.

Toward a Theory of Structure in Information Organization Frameworks

This paper outlines a formal and systematic approach to explication of the role of structure in information organization. It presents a preliminary set of constructs that are useful for understanding the similarities and differences that obtain across information organization systems. This work seeks to provide necessary groundwork for development of a theory of structure that can serve as a lens through which to observe patterns across systems of information organization.

Biomarker evaluation and toxicological study of essential oils of Foeniculum vulgare and Calamintha nepeta

The aim of this study was to evaluate the toxicological properties of EOs of F. vulgare and C. nepeta, widespread in Mediterranean agrosilvopastoral systems and often used as food condiments in Alentejo. EOs were obtained from aerial part of plants by hydrodistillation and chemical composition was evaluated by GC-FID. Toxicity of essential oils was evaluated by the estimation of LC50 in brine shrimp and LD50 in mice. Oral toxicity assays were performed in mice. Histological analyses and quantification of biomarkers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyltransferase (γ-GT), bilirubin, creatinine and urea were performed for monitoring liver and kidney functions. the EOs of C. nepeta and F. vulgare showed very low toxicity suggesting their potential use as food supplement. Additionally, our studies point out the importance of the integration of C. nepeta and F. vugare in silvopastoral agroforestry systems, contributing to the animal health and profitability of livestock.

Genesis and classification of soils from subtropical mountain regions of Southern Brazil.

Soils formed in high mountainous regions in southern Brazil are characterized by great accumulation of organic matter (OM) in the surface horizons and variation in the degree of development. We hypothesized that soil properties and genesis are influenced by the interaction of parent materials and climate factors, which differ depending on the location along the altitudinal gradient. The goal of this study was to characterize and classify the soil, evaluate soil distribution, and determine the interactive effects of soil-forming factors in the subtropical mountain regions in Santa Catarina state. Soil samples were collected in areas known for wine production, for a total of 38 modal profiles. Based on morphological, physical, and chemical properties, soils were evaluated for pedogenesis and classified according to the Brazilian System of Soil Classification, with equivalent classes in the World Reference Basis (WRB). The results indicated that pedogenesis was strongly influenced by the parent material, weather, and relief. In the areas where basic effusive rocks (basalt) were observed, there was formation of extensive areas of clayey soils with reddish color and higher iron oxide contents. There was a predominance of Nitossolos Vermelhos and Háplicos (Nitisols), Latossolos Vermelhos (Ferralsols), and Cambissolos Háplicos (Cambisols), highlighting the pedogenetic processes of eluviation, illuviation of clay, and latosolization in conditions of year-long, large-volume, well-distributed rainfall and stability of land forms. In areas with acid effusive rocks (rhyodacites), medial or clayey soils were observed with lower iron oxide content, invariably acidic, and with low base content. For these soils, relief promoted substantial removal of material, resulting in intense rejuvenation, with a predominance of Cambissolos Háplicos (Cambisols) and lesser occurrence of Nitossolos Brunos (Nitisols) and Neossolos Litólicos (Leptosols). Soils formed from sedimentary rocks also tended to be more acidic, but with higher sand content, and the soils identified were Cambissolos Háplicos and Húmicos (Cambisols). Cluster analysis separated the soil profiles into three groups: the first and largest was formed by profiles originating from sedimentary rocks and rhyodacites; the second, smaller group was formed by four profiles in the Água Doce region (acidic rocks); and the third was formed by profiles derived from basalt. Discriminant analysis was effective in grouping soil classes. Thus, the study highlighted the importance of geology in the formation of soils in this landscape associated with climate and relief.

Using narrow beam profiles to quantify focal spot size, for accurate Monte Carlo simulations of SRS/SRT systems

This study investigates the variation of photon field penumbra shape with initial electron beam diameter, for very narrow beams. A Varian Millenium MLC (Varian Medical Systems, Palo Alto, USA) and a Brainlab m3 microMLC (Brainlab AB. Feldkirchen, Germany) were used, with one Varian iX linear accelerator, to produce fields that were (nominally) 0.20 cm across. Dose profiles for these fields were measured using radiochromic film and compared with the results of simulations completed using BEAMnrc and DOSXYZnrc, where the initial electron beam was set to FWHM = 0.02, 0.10, 0.12, 0.15, 0.20 and 0.50 cm. Increasing the electron-beam FWHM produced increasing occlusion of the photon source by the closely spaced collimator leaves and resulted in blurring of the simulated profile widths from 0.26 to 0.64 cm, for the MLC, from 0.12 to 0.43 cm, for the microMLC. Comparison with measurement data suggested that the electron spot size in the clinical linear accelerator was between FWHM = 0.10 and 0.15 cm, encompassing the result of our previous output-factor based work, which identified a FWHM of 0.12. Investigation of narrow-beam penumbra variation has been found to be a useful procedure, with results varying noticeably with linear accelerator spot size and allowing FWHM estimates obtained using other methods to be verified.

Optical assessment of impact and recovery of sedimentary pH profiles in ocean acidification and carbon capture and storage research

Available methods for measuring the impact of ocean acidification (OA) and leakage from carbon capture and storage (CCS) on marine sedimentary pH profiles are unsuitable for replicated experimental setups. To overcome this issue, a novel optical sensor application is presented, using off-the-shelf optode technology (MOPP). The application is validated using microprofiling, during a CCS leakage experiment, where the impact and recovery from a high CO2 plume was investigated in two types of natural marine sediment. MOPP offered user-friendliness, speed of data acquisition, robustness to sediment type, and large sediment depth range. This ensemble of characteristics overcomes many of the challenges found with other pH measuring methods, in OA and CCS research. The impact varied greatly between sediment types, depending on baseline pH variability and sediment permeability. Sedimentary pH profile recovery was quick, with profiles close to control conditions 24 h after the cessation of the leak. However, variability of pH within the finer sediment was still apparent 4 days into the recovery phase. Habitat characteristics need therefore to be considered, to truly disentangle high CO2 perturbation impacts on benthic systems. Impacts on natural communities depend not only on the pH gradient caused by perturbation, but also on other processes that outlive the perturbation, adding complexity to recovery.