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Pre-clinical evaluation of the possible enhancement of the efficacy of antiretroviral drugs by pheroid technology / M.M. BothaBotha, Mario Matthew January 2007 (has links)
HIV/AIDS is the most threatening and challenging infectious diseases of our time, with the highest increase of newly infected cases reported. This infectious disease was discovered in the early eighties under homosexual men and was later to be discovered in heterosexuals. HIV is a systemic immunosuppressive disorder which causes a depletion of CD4+ T cells and develops into the acquired immunodeficiency syndrome - AIDS.
Africa is the continent most affected by HIV/AIDS with the southern parts of Africa having the highest prevalence rates compared to the rest of Africa. Statistics indicate that AIDS is responsible for 3% of deaths in children worldwide - one in seven people dying of an HIV-related illness is a child under the age of 15 years. It was stated by the WHO that countries should develop improved antiretrovirals regimes for the prevention of mother-to-child transmission.
Difficulties in administering antiretrovirals (ARVs) to patients (especially children) are the strict dosage regimes and the severe adverse reactions. These factors complicate patient adherence. The list of problems in treating patients is endless and includes the distribution, stability as well as the low efficacy of these drugs.
Most of the above mentioned problems and obstacles related to ARVs and ARV treatment could be minimized or eliminated by the use of a stable and effective drug delivery system. Enhancing ARV treatment may be accomplished by the use of the Pheroid™ drug delivery system. Pheroids™ consists mainly of fatty acids and sterile nitrous oxide gassed water. Pharmacological active substances are entrapped into submicron and micron sized structures called Pheroids™. Research showed promising results and advantages in delivering drugs through oral and transdermal routes using Pheroid™ technology.
The focus of this study was to test the possible enhancement of the efficacy of antiretrovirals using Pheroid™ technology. The assays used to study this possible enhancement were a modified neutral red and a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. These assays confirmed and illustrated the toxic and protective properties of the tested ARVs (stavudine, lamivudine and nevirapine). An MT-2 cell line was used and infected with an HIV-1 strain, SW7-TCL.
Applying Pheroid™ technology in these assays resulted in massive cell death, due to increased ARV toxic levels within the cells. Viability tests proved that Pheroids™ had no effect on the viability of cells at the concentration typically used. This confirmed the enhancing properties of Pheroids™ in the delivery of drugs into the cells. The MTT assay was further adapted from a seven day incubation period to a three day incubation period. By using a low concentration series and a three day incubation period the loss of cells through toxicity was partially overcome.
One of the problems that arose form this study was the non-reproducibility of the results. Absorbance levels fluctuated at specific concentrations of the same ARV, which cause difficulties in comparing results. This result was repeatedly confirmed in this syncytium forming infection model.
In conclusion, Pheroid™ technology enhanced the delivery of ARVs into the cells although it resulted in cell death. Both the neutral red and MTT assays were found to be inaccurate but further development, research and assay optimization could result in improved in vitro studies.
The article format was used for this thesis, as described in the general academic rules in section A.13.7.3 of the North West University. Chapter 1 deals with HIV/AIDS related problems, statistics and treatment obstacles. Chapter 2 is a summary of the cell viability assays used in this study. Pheroid™ technology and its application to ARV treatment are dealt with in chapter 3. The proposed article for submission in the journal Cell Death and Differentiation has been included in chapter 4. Some of the results from the study are reported in the article and annexures, whilst other results are shown and discussed in Chapter 5. Chapter 6 gives a conclusion and final summary of this study. All other experimental methods and results are enclosed in the annexures, as is the "Guide for authors" for the article. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.
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From giants to dwarfs : probing the edges of galaxiesPortas, Antonio Miguel Pereira January 2010 (has links)
In this thesis we address fundamental questions about what constitutes and limits an HI disc, probing the distribution of neutral gas in the outer parts of galaxies. We use a subsample of galaxies observed as part of the THINGS survey to investigate the HI extent of spiral galaxy discs. We revisit previous work on the extent of HI discs, showing the limitations set by insufficient linear resolution. We then exploit the high spatial and velocity resolution combined with good sensitivity of THINGS to investigate where the atomic gas discs end and what might shape their edges. We find that the atomic gas surface density across most of the disc is constant at 5 – 10 x 10^20 atoms/cm^2 and drops sharply at large radius. The general shape of the HI distribution is well described by a Sérsic-type function with a slope index, n = 0.14 - 0.22 and characteristic radius ri. We propose a new column density threshold of 5 x 10^19 atoms/cm^2 to define the extent of the gas disc. This limit is well within reach of modern instruments and is at the level where disc gas becomes susceptible to ionisation by an extragalactic radiation field. We argue that at this level the HI column density has decreased to one tenth of that across the inner disc and that by going to yet lower column density the disc is unlikely to grow by more than 10% in radius. The HI column density at which the radial profiles turn over is too high for it to be caused by ionisation by an extragalactic UV field and we postulate that the HI extent is set by how galaxy discs form. Ionisation by extragalactic radiation will only play a rôle at column densities below 5 x 10^19 atoms/cm^2, if any. To study the crucial relation between observed edges and how closely these reproduce the intrinsic distribution of gas through our interferometric measurements, we created an ensemble of models based on four radial density distributions. We conclude that the observed edges in spiral galaxies faithfully reflect their intrinsic shape. Only in very specific cases of highly inclined (>75º) and/or large vertical scaleheight discs do we see strong deviations from the intrinsic surface density of the observed shape of the edges in spiral galaxies. In the case of NGC 3198 we concluded that there is no significant difference in the radial profiles obtained with either constant or exponentially increasing vertical gas distributions, when scaleheights are not higher than 1 kpc at the outskirts of the disc. We infer an upper limit to the scaleheight of NGC 3198 of 2 kpc. To address the distribution of neutral gas at larger scales, we study an HI rich, giant LSB galaxy, NGC 765. We present HI spectral line and radio-continuum VLA data, complemented by optical and Chandra X-ray maps. NGC 765 has the largest HI-to-optical ratio known to date of any spiral galaxy and one of the largest known HI discs in absolute size with a diameter of ~ 240 kpc measured at a surface density of 2 x 10^19 atoms/cm^2. We derive a total HI mass of M_HI = 4.7 x 10^10 M_sun, a dynamical mass of M_dyn = 5.1 x 10^11 M_sun and an HI mass to luminosity ratio of M_HI/L_B = 1.6, making it the nearest and largest “crouching giant”. Optical images reveal evidence of a central bar with tightly wound low-surface brightness spiral arms extending from it. Radio-continuum (L_1.4 GHz = 1.3 x 10^21 W/Hz) and X-ray (L_x ~ 1.7 x 10^40 erg/s) emission is found to coincide with the optical core of the galaxy, compatible with nuclear activity powered by a low-luminosity AGN. We may be dealing with a galaxy that has retained in its current morphology traces of its formation history. In fact, it may still be undergoing some accretion, as evidenced by the presence of HI clumps the size (< 10 kpc) and mass (10^8 -10^9 M_sun) of small (dIrr) galaxies in the outskirts of its HI disc and by the presence of two similarly sized companions. In an exploration of future work, we engaged in a study of the edges in the HI discs of dwarf irregular galaxies, their parameterisation and simulation. A collection of simulations were created based on the dwarf galaxy NGC 2366, similar to what was done for the larger spiral galaxies, showing that line-of-sight column densities are affected for discs with inclinations higher than 60º. Five out of eleven of the dwarfs from THINGS which are less inclined than 60º were analysed and parameterised with our Sérsic-type function. Their discs have average central column densities spread evenly from log_10 NHI = 20.7 atoms/cm^2 to log_10 NHI =21.3 atoms/cm^2. Their radial decline is shallower (slope index peaks around n ~ 0.3) than for spirals. The up-coming Local Irregular That Trace Local Extremes (LITTLE) THINGS project, will likely enlarge the number of local dwarf irregular (dIm) galaxies to which this type of analysis can be applied and for which these preliminary results verified.
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Shells, bubbles and holes : the porosity of the interstellar medium in galaxiesBagetakos, Ioannis January 2012 (has links)
We present an analysis of the properties of HI holes detected in 20 galaxies that are part of “The HI Nearby Galaxy Survey” (THINGS). We detected more than 1000 holes in total in the sampled galaxies. Where they can be measured, their sizes range from about 100 pc (our resolution limit) to about 2 kpc, their expansion velocities range from 4 to 36 km/s, and their ages are estimated to range between 3 and 150 Myr. The holes are found throughout the discs of the galaxies, out to the edge of the HI disc; 23% of the holes fall outside R25. We find that shear limits the age of holes in spirals; shear is less important in dwarf galaxies which explains why HI holes in dwarfs are rounder, on average than in spirals. Shear, which is particularly strong in the inner part of spiral galaxies, also explains why we find that holes outside R25 are larger and older. We derive the scale height of the HI disc as a function of galactocentric radius and find that the disc flares at large radii in all galaxies. We proceed to derive the surface and volume porosity (Q2D and Q3D) and find that this correlates with the type of the host galaxy: later Hubble types tend to be more porous. The size distribution of the holes in our sample follows a power law with a slope of a=−2.9. Assuming that the holes are the result of massive star formation, we derive values for the supernova rate (SNR) and star formation rate (SFR) which scales with the SFR derived based on other tracers. If we extrapolate the observed number of holes to include those that fall below our resolution limit, down to holes created by a single supernova, we find that our results are compatible with the hypothesis that HI holes result from star formation. We use HI data from THINGS, 8μm, 24μm, 70μm and HI maps from SINGS, CO(2–1) data from HERACLES and FUV data from NGS to present a visual comparison of these maps with respect to the locations of HI holes. We find that the vast majority of HI holes are also prominent in the 8μm map and to some extent in the 24μm map. There is a lack of molecular gas from the interior of nearly all the holes, which is consistent with the idea that the latter are filled with hot gas. About 60% of young holes have FUV emission detected in their interiors highlighting the presence of the parent OB association. In addition, FUV is detected on the rims of some of the older HI holes, presumably due to the dispersion of the OB association with respect to the gas. We describe the development of a 2–D cross-correlation method to compare multi-wavelength maps in a quantitative way (quantified by Ccoef ) and give some first results from the application of this method to the nearby galaxy NGC2403. We find that the all the dust tracers are well correlated (Ccoef > 0.7) with the 8μm–24μm correlation being the highest (Ccoef > 0.88). Similarly all the star formation tracers are well linked as expected (Ccoef > 0.6). With respect to the relations between star formation and dust tracers we found that most are well matched (Ccoef > 0.7) as dust grains are heated by radiation in star forming regions. At smaller scales (15") FUV correlates poorly (Ccoef ~ 0.3) with the dust tracers, a direct consequence of the absorption of FUV photons by dust. We find that the HI is reasonably well correlated with the 8μm emission (Ccoef ~ 0.6) illustrating the fact that HI is mixed with PAH’s. Interestingly, the HI map shows some correlation with the SF map (Ccoef ~ 0.4) even though FUV and HI emissions were found to be completely uncorrelated (Ccoef ~ 0).
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Quantum Control and Quantum Tomography on Neutral Atom QuditsSosa Martinez, Hector, Sosa Martinez, Hector January 2016 (has links)
Neutral atom systems are an appealing platform for the development and testing of quantum control and measurement techniques. This dissertation presents experimental investigations of control and measurement tools using as a testbed the 16-dimensional hyperfine manifold associated with the electronic ground state of cesium atoms. On the control side, we present an experimental realization of a protocol to implement robust unitary transformations in the presence of static and dynamic perturbations. We also present an experimental realization of inhomogeneous quantum control. Specifically, we demonstrate our ability to perform two different unitary transformations on atoms that see different light shifts from an optical addressing field. On the measurement side, we present experimental realizations of quantum state and process tomography. The state tomography project encompasses a comprehensive evaluation of several measurement strategies and state estimation algorithms. Our experimental results show that in the presence of experimental imperfections, there is a clear tradeoff between accuracy, efficiency and robustness in the reconstruction. The process tomography project involves an experimental demonstration of efficient reconstruction by using a set of intelligent probe states. Experimental results show that we are able to reconstruct unitary maps in Hilbert spaces with dimension ranging from d=4 to d=16. To the best of our knowledge, this is the first time that a unitary process in d=16 is successfully reconstructed in the laboratory.
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The Effects of News Commentary on the Image of Political Debaters: An Experimental StudyHertzog, Robert L. 12 1900 (has links)
The purpose of this study was to examine the effects of news commentary on the image of political candidates. Subjects were exposed to a political debate, which was followed by three experimental manipulations of a news commentary. One group saw a commentary biased toward one candidate and against the other. In a second group the bias was reversed. A third experimental group saw a neutral commentary and the control group viewed the debate but no commentary. The primary statistical analyses used were a multivariate analysis of variance, a multiple discriminant analysis and a factor analysis.
The results indicated that the commentary did have some effects on the perception of the candidates' images. Furthermore, the commentaries affected the amount of the candidates' message which was recalled by the subjects, and cued the subjects to recall specific issues which were mentioned in the commentaries. Finally, the factor analysis indicated certain characteristics of the images of political candidates.
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”Jag har aldrig trott på censur och kommer aldrig att göra” : En studie om samsynen mellan lärare och elev gällande politisk objektivitet i undervisningenJonsson, Alex January 2019 (has links)
The Swedish educational system is based on policies such as school law, education act, regulations and the curriculum. These governing documents state that the education should be based on scientific basis and proven experience. However, a lack of education with terms such as non-objective and value free, there is room for interpretation and variety of views. There is a media debate in which different opinions are being expressed whether the teacher should remain objective or not while teaching. A topic such as social science, is interesting to research within political objectivity. How teachers perceive their professional role, maintain balance between objectivity, freedom of expression, and carefor the school’s value. Thanks to interviews with teachers at various upper secondary schools, the essay shares an insight of the teachers’ perceptions. A questionnaire survey was used to help compare how students’ perceive their teachers’ objectivity. This wasused to investigate how and if the teachers’ interpretation of the policies corresponds toreality. The interviews provided a clear consensus that the teachers consider objectivity to be self- evident in discussions of Swedish politics. However, if students’ express opinions which are not in line with the values of the Swedish school-system the teachers believe that they hold a key-role in providing moral guidance which the swedish school system provides and shield. Furthermore there is also a clear consensus in the interpretation of the teachers profession which inherently contains a zero-tolerance policy towards racism and expressions that claim people to be of different values. At the same time as the students’ education is a tool for them to be a part of the democratic system, the students should at all times be given two perspectives in the same field for their ability to create their own views and values.
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O corpo neutro / -Barrocas, Filipe Miguel dos Santos 01 December 2015 (has links)
O autor explora o corpo neutro do referente da imagem fotográfica e o resultado da sua pesquisa é este conjunto de narrativas. Cada uma é construída a partir dos retratos da família e desenvolvida em diálogo com outros autores. Ele conta em particular a história de um homem e de uma mulher. Mas eles não são um casal. Ele é avô dela. E ela, ainda criança nestas imagens, é agora mãe do autor. Ele lê no verso do retrato dela: \"Vimeiro 1968\". É a costa ocidental portuguesa. Lugar onde se travou a batalha com os franceses no início do século XIX e, pelo que parece, destino de férias da sua família. Lugar esperado e distante, onde águas doces e salgadas se encontram e a ilha de Saturno pontua o horizonte. Ilha granítica situada no oceano Atlântico, a meia dúzia de milhas do Cabo Carvoeiro. No horizonte do Vimeiro, onde o avô ensinou a criança a nadar. Acontecimento testemunhado pelo aparelho fotográfico do pai e comprovado até hoje pelos retratos do álbum da família. Nestas férias o avô ensinou-a a nadar e o seu pai foi fotógrafo, a avó cozinhou e a mãe costurou um sorriso, não fosse ter chorado na Rocha do Conde de Óbidos quando ele embarcou no paquete Pátria da Companhia Nacional de Navegação no dia 29 de Agosto de 1961. / The author explores the referent\'s neutral body in the photographic image and the result of his research is this set of narratives, each one built from the family\'s portraits and the dialogue with other authors. He tells in particular the story of a man and a woman. They are not a couple though. He is her grandfather and she, a child in these images, is now the author\'s mother. He reads on the back of her picture, \"Vimeiro 1968\". It is the Portuguese west coast. Where the battle with the French was fought in the early nineteenth century and, it seems, his family\'s vacation destination. Expected and distant place, where fresh and salt waters meet and Saturno Island punctuates the horizon. Granitic island situated in the Atlantic Ocean, half a dozen miles from Cabo Carvoeiro. In the horizon of Vimeiro where the grandfather taught the children to swim. Event witnessed by the father\'s photographic apparatus and today testified by the pictures in the family\'s album. This holiday grandfather taught her to swim, father was photographer, grandmother cooked, and mother sewed a smile, had not she wept in Rocha do Conde de Óbidos when he boarded the packet Pátria, of Companhia Nacional de Navegação, on August 29, 1961.
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Análise da interoperabilidade de dados para a implementação de um ambiente de manufatura virtual / Analysis of data interoperability for a virtual manufacturing environment implementationRavelli, Carlos Alberto 15 May 2003 (has links)
Apresenta uma análise sobre requisitos de interoperabilidade de dados na cadeia de desenvolvimento do produto e processo em empresas dos setores automotivo e máquinas rodoviárias, relacionados com a implementação da manufatura virtual. As informações foram coletadas de livros, artigos de conferências, revistas, páginas da internet, e discussões com especialistas. Descreve as principais características de formatos neutros de dados e núcleos de modelagem de sistemas. Aborda a viabilidade na padronização dos requisitos de informação e representação de dados, de maneira a selecionar uma relação de formatos neutros para a troca de dados compatíveis para uma variedade de sistemas da manufatura virtual. Relata os principais esforços no desenvolvimento de formatos neutros para a melhoria da interoperabilidade de dados. / This paper presents an interoperability requirement analysis of the product and process development chain for automotive and off-road vehicle factories for a virtual manufacturing implementation. All information was collected from articles, technical magazines, internet, books, and discussion with specialists. A description is given of major features of neutral data formats and system modeling kernels. Also provided is an analysis of the feasibility of standardizing the informational needs of virtual manufacturing systems. Finally a representation of input data is presented in order to select neutral data formats suitable for a variety of virtual Manufacturing systems. The paper concludes by reporting the major worldwide efforts on developing neutral data standards to improve interoperability.
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Jogo e memória: essências - cena contemporânea e o jogo do círculo neutro como anteparos para os processos de preparação e criação do ator / Game and Memory: Essences - Contemporary Scene and the Neutral Circle game as support for the actors\' processes of preparation and creationJosé Eduardo de Paula 06 November 2015 (has links)
A pesquisa utiliza a Cena Contemporânea (2011-2013) e o jogo do Círculo Neutro como anteparos para os processos de preparação e criação do ator. Primeiro, procura refletir sobre os ambientes formativos, relacionando as proposições de Agamben sobre o \"ser qualquer [e o] assim, irreparável\" (1993), com as de Bauman sobre \"comunidade, segurança, liberdade e estrangeiro\" (2003). Segundo, busca cartografar o Círculo Neutro e, para isso, entrevista François Kahn, Francisco Medeiros, Inês Aranha e Maurício Paroni de Castro. Depois, junto a um grupo de atores, instala um campo de verificação prático e experimental para vivenciar, derivar, descrever e enquadrar o Círculo Neutro como \"jogo\". Considera que o jogo e o jogar, portadores dos aspectos risco, acidente e imprevistos, mostram-se produtivos para o trabalho do ator e para o desenvolvimento orgânico da cena, pois colaboram para a formação de um artista mais \"aberto\" e com \"jogo de cintura\". / The study uses the Contemporary Scene (2011-2013) and the Neutral Circle game as support for the actors\' processes of preparation and creation. Firstly, it aims at reflecting about the education environments by relating the propositions of Agamben about the \"whatever being [and the] therefore, irreparable\" (1993), with those of Bauman about \"community, safety, freedom and foreign\" (2003). Secondly, it tries to map the Neutral Circle, and for that interviews François Khan, Francisco Medeiros, Inês Aranha, and Maurício Paroni de Castro. Afterwards, with a group of actors, it establishes a space of practical and experimental verification to experience, derive, describe and frame the Neutral Circle as a \"game\". The analysis considers that the game and the act of playing, involving the aspects of risk, accident and the unexpected, are productive for the work of the actor and for the organic development of the scene, because they collaborate with the formation of an artist who is more \"open\" and \"more flexible\".
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Imputação das ações neutras e o dever de solidariedade no direito penal brasileiro / Neutral or daily actions imputation and the obligation of solidarity on the Brazilian criminal lawRassi, João Daniel 27 April 2012 (has links)
A presente tese se propõe a analisar os limites entre a participação criminal e a conduta impune, com o objetivo de enfrentar a problemática das chamadas ações neutras, a partir do fundamento do injusto da participação criminal. Para tanto, são expostas as diversas teorias que explicam o injusto do partícipe, entre as quais é feita opção pela mais adequada à sistemática brasileira do concurso de pessoas, a qual servirá de base para a apresentação do próprio ponto de vista para resolver a questão da punibilidade das condutas a priori neutras. A teoria da imputação objetiva foi considerada como um instituto essencial na análise da participação criminal, o que permitiu a abordagem sobre o desvalor da conduta do partícipe como objeto de imputação. O desvalor da conduta do partícipe, por sua vez, foi entendido como uma violação do dever de solidariedade, o que implicou no tratamento da solidariedade humana objetiva como elemento imprescindível para a existência social coesa, a partir do pensamento de Durkheim e Giddens. Por fim, aceitando o pressuposto de que nem todos são responsáveis pelo comportamento alheio, a omissão penalmente relevante foi estudada como critério capaz de limitar a responsabilidade penal no caso em que há concurso de pessoas para a prática de crime, na discussão do seu limite mínimo. / The present work aims to analyze the boundaries between the criminal participation and non-punishable conducts, with the intention of addressing the question of the so-called neutral or daily actions, from the standpoint of the unjust of the criminal participation. To this effect, the work begins by exposing the numerous theories that explain the unjust of the criminal participation. The study is then limited to the one that best fits the Brazilian law regarding concerted actions, which will then be used as grounds to the authors point of view to address the issue of the punishment of the actions that a priori are daily or neutral. The theory of objective imputation was considered essential to the analysis of the criminal participation, thus allowing the study of the social disapproval of the conduct of the accessory as the object of criminal imputation. The social disapproval of the conduct of the accessory, on the other hand, was seen as a breach in the obligation of solidarity, which resulted in objective human solidarity being considered a fundamental element to a cohesive social existence, as stated by Durkheim and Giddens. Finally, according to the assumption that not everyone is responsible for other peoples behavior, relevant criminal omission was studied as a criteria to restrict criminal liability in concerted actions, when debating its minimal limit.
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