Preparação, caracterização e propriedades de lipossomas contendo o ácido -ciano-4-hidroxicinâmico e o agente fotossenbilizador AICIPc: um novo sistema carreador específico com ação sinérgica aplicado a terapia fotodinâmica

Ftalocianina de alumínio-cloro (AlClPc) é um fotossensibilizador de segunda geração em terapia fotodinâmica (TFD) caracterizado por seu caráter anfifílico e tendência de auto-agregação em meio aquoso, o que prejudica seu potencial de aplicação. O aCHC é um substrato de transportadores de monocarboxilato (MCT) superexpresso em células de MCF-7. Objetivando a solubilização da AlClPc e aumento de internalização em tecidos neoplásicos nos propomos aqui o uso de DSPC e DOPC em diferentes proporções para formar vesículas lipidicas mistas (LV) na presença de aCHC como sistemas veiculadores de fármaco. Lv foi preparado pelo método de injeção etanólica e formou vesículas de dimensões nanométricas (aproximadamente 100 nm) com bom índice de polidispersão, valores negativos de potencial zeta e estáveis em meio aquoso por mais de 50 dias. AlClPc se complexou com o fosfato das LV o que conferiu uma localização interfacial às moléculas de AlClPc como demonstrado pelos resultados de supressão de fluorescência. Medidas de anisotropia, fluorescência estática e resolvida no tempo corroboram com estes resultados e demonstram que a auto-agregação da AlClPc ocorre mesmo em lipossomas. Entretanto, a veiculação da AlClPc por LV em carcinoma de células escamosas oral (OSCC) levou a um processo de desagregação demonstrado por (FLIM). Este incrível comportamento é novo e aumenta o conhecimento científico sobre o mecanismo intracelular de ação de fotossensibilizadores em TFD. Em TFD, ambos os sistemas LVIII+AlClPc e LVIII+AlClPc+aCHC não apresentaram toxicidade no escuro no período de incubação de 3 h com as concentrações de lipídios, AlClPc e aCHC iguais a 0,15 mmol/L, 0,5 umol/L e 10,0 umol/L, respectivamente. De maneira inesperada, o sistema LVIII+AlClPc foi mais eficiente em TFD que o sistema LVIII+AlClPc+aCHC, devido ao caráter antioxidante do aCHC. Estes resultados abrem uma nova perspectiva do potencial uso de LV-AlClPc para o tratamento fotodinâmico.

Proline and pyrrolidine derivatives: new drug cadidates for hepatitis C treatment

The more advantageous hepatitis C virus (HCV) inhibitors (most of them incorporating polysubstituted prolines or pyrrolidines) are detailed in this paper. The improvement of current treatments by combination of antiviral drugs is the driving force of this race to reduce the fast proliferation of this virus. The enhancement of efficiency in short periods of treatment is crucial in the economical point of view and for the hope of all infected people. New protease or polymerase inhibitors have been recently developed in order to substitute the traditional highly toxic PEG-interferon α-2b/ribavirin tandem. The contribution of our group in this field concerns the elaboration of the first and second generation GSK polymerase inhibitors through enantioselective processes based on silver(I)- and gold(I)-catalyzed 1,3-dipolar cycloadditions of azomethine ylides.

Direitos sociais na Constituição: uma análise da constitucionalização dos direitos sociais em Portugal, 1975-76

Embora todas as constituições incluam direitos, e muitas delas incluam direitos sociais, a verdade é que algumas são mais generosas do que outras a este respeito. Mas nenhuma se aproxima da Constituição da República Portuguesa de 1976 no que toca à extensão e detalhe do seu catálogo de direitos sociais, económicos e culturais. As principais teorias sobre as origens de instituições geraram hipóteses explicativas da constitucionalização desta segunda geração de direitos. Sucede, porém, que estas hipóteses não conseguem explicar de forma totalmente convincente o processo de constitucionalização dos direitos sociais. Isto é ainda mais verdade em casos como o do nosso país, cujo carácter discrepante os tornam ainda mais difíceis de explicar. Neste artigo, estas teorias e respectivas hipóteses serão testadas por relação ao caso português o qual será, sempre que se revelar necessário, comparado com o espanhol. Visamos alcançar dois objectivos com este exercício. Por um lado, pretendemos identificar as limitações das explicações dominantes, incluindo as teorias e hipóteses sobre os mecanismos causais responsáveis pela inclusão de direitos sociais nas constituições. Por outro lado, o nosso propósito é o de conceber explicações alternativas sempre que as existentes se revelem inadequadas ou insuficientes.

Going live: a comparative analysis of the suitability of the RFP derivatives RedStar, mCherry and tdTomato for intravital and in vitro live imaging of Plasmodium parasites

Fluorescent proteins have proven to be important tools for in vitro live imaging of parasites and for imaging of parasites within the living host by intravital microscopy. We observed that a red fluorescent transgenic malaria parasite of rodents, Plasmodium berghei-RedStar, is suitable for in vitro live imaging experiments but bleaches rapidly upon illumination in intravital imaging experiments using mice. We have therefore generated two additional transgenic parasite lines expressing the novel red fluorescent proteins tdTomato and mCherry, which have been reported to be much more photostable than first- and second-generation red fluorescent proteins including RedStar. We have compared all three red fluorescent parasite lines for their use in in vitro live and intravital imaging of P. berghei blood and liver parasite stages, using both confocal and wide-field microscopy. While tdTomato bleached almost as rapidly as RedStar, mCherry showed improved photostability and was bright in all experiments performed.

Memorias en voz baja : Transmisión oral intergeneracional: de Os libros arden mal a As voces baixas

Este trabajo analiza la forma en que se desarrolla un traspaso de la experiencia del pasado traumático en dos textos de Manuel Rivas en los que adquiere gran protagonismo el discurso oral. La Guerra Civil española y sus consecuencias son incorporadas a la narrativa de Os libros arden mal y As voces baixas con especial énfasis en las generaciones que no vivieron esos años. Las convergencias entre oralidad y escritura resultan un terreno fértil para considerar la inclusión de voces largamente postergadas debido a silencios impuestos y a la represión de verdades que tardaron en visibilizarse.

Wounds in the rain: war stories,

The price of the harness.--The lone charge of William B. Perkins.--The clan of No-name.--God rest ye, merry gentlemen.--The revenge of the Adolphus.--The sergeant's private madhouse.--Virtue in war.--Marines signalling under fire at Guantanamo.--This majestic lie.--War memories.--The second generation.

Mental Health Experiences within the Hmong American LGBTQ Community: A Qualitative Research Project

Thesis (Master's)--University of Washington, 2016-06

The genetic covariance among clinal environments after adaptation to an environmental gradient in Drosophila serrata

We examined the genetic basis of clinal adaptation by determining the evolutionary response of life-history traits to laboratory natural selection along a gradient of thermal stress in Drosophila serrata. A gradient of heat stress was created by exposing larvae to a heat stress of 36degrees for 4 hr for 0, 1, 2, 3, 4, or 5 days of larval development, with the remainder of development taking place at 25degrees. Replicated lines were exposed to each level of this stress every second generation for 30 generations. At the end of selection, we conducted a complete reciprocal transfer experiment where all populations were raised in all environments, to estimate the realized additive genetic covariance matrix among clinal environments in three life-history traits. Visualization of the genetic covariance functions of the life-history traits revealed that the genetic correlation between environments generally declined as environments became more different and even became negative between the most different environments in some cases. One exception to this general pattern was a life-history trait representing the classic trade-off between development time and body size, which responded to selection in a similar genetic fashion across all environments. Adaptation to clinal environments may involve a number of distinct genetic effects along the length of the cline, the complexity of which may not be fully revealed by focusing primarily on populations at the ends of the cline.

Biology of the leech Actinobdella inequiannulata Moore, 1901 (Annelida: Hirudinea: Rhynchobdellida: Glossiphoniidae), parasitic on the white sucker, Catostomus commersoni Lacepede, 1803, and the longnose sucker, Catostomus catostomus Forster, 1773, in Algonquin Provincial Park, Ontario, Canada

Actinobdella inequiannulata was found on the white sucker. Catostomus commersoni, and less frequently on the longnose sucker, Catostomus catostomus, in Algonquin Provincial Park, Ontario, Canada. Catostomus commersoni parasitized with Act. inequiannulata was collected from July to October 1973 and May to October 1974. In May and October, less than 3% of the fish carried leeches. In July, 80% of the fish were parasitized with an average of 1.5 leeches/fish. Observations on leech weight suggest that young leeches attach to fish from May to September, some mature in July, and a second generation of leeches reparasitize the fish in August and September. The mean size of leeches on suckers increased from May until July, after which the size remained relatively constant. Leeches produced characteristic lesions on the opercula of suckers. Fully developed lesions on fish opercula produced by aggregated leeches had varying amounts of central erosion, extravasation, dermal and epidermal hyperplasia, and necrosis.

Digital video transmission over wireless networks

The advent of the Integrated Services Digital Network (ISDN) led to the standardisation of the first video codecs for interpersonal video communications, followed closely by the development of standards for the compression, storage and distribution of digital video in the PC environment, mainly targeted at CD-ROM storage. At the same time the second-generation digital wireless networks, and the third-generation networks being developed, have enough bandwidth to support digital video services. The radio propagation medium is a difficult environment in which to deploy low bit error rate, real time services such as video. The video coding standards designed for ISDN and storage applications, were targeted at low bit error rate levels, orders of magnitude lower than the typical bit error rates experienced on wireless networks. This thesis is concerned with the transmission of digital, compressed video over wireless networks. It investigates the behaviour of motion compensated, hybrid interframe DPCM/DCT video coding algorithms, which form the basis of current coding algorithms, in the presence of high bit error rates commonly found on digital wireless networks. A group of video codecs, based on the ITU-T H.261 standard, are developed which are robust to the burst errors experienced on radio channels. The radio link is simulated at low level, to generate typical error files that closely model real world situations, in a Rayleigh fading environment perturbed by co-channel interference, and on frequency selective channels which introduce inter symbol interference. Typical anti-multipath techniques, such as antenna diversity, are deployed to mitigate the effects of the channel. Link layer error control techniques are also investigated.

Efficiency improvements to the Groupe Special Mobile (GSM) digital mobile radio system

Groupe Spécial Mobile (GSM) has been developed as the pan-European second generation of digital mobile systems. GSM operates in the 900 MHz frequency band and employs digital technology instead of the analogue technology of its predecessors. Digital technology enables the GSM system to operate in much smaller zones in comparison with the analogue systems. The GSM system will offer greater roaming facilities to its subscribers, extended throughout the countries that have installed the system. The GSM system could be seen as a further enhancement to European integration. GSM has adopted a contention-based protocol for multipoint-to-point transmission. In particular, the slotted-ALOHA medium access protocol is used to coordinate the transmission of the channel request messages between the scattered mobile stations. Collision still happens when more than one mobile station having the same random reference number attempts to transmit on the same time-slot. In this research, a modified version of this protocol has been developed in order to reduce the number of collisions and hence increase the random access channel throughput compared to the existing protocol. The performance evaluation of the protocol has been carried out using simulation methods. Due to the growing demand for mobile radio telephony as well as for data services, optimal usage of the scarce availability radio spectrum is becoming increasingly important. In this research, a protocol has been developed whereby the number of transmitted information packets over the GSM system is increased without any additional increase of the allocated radio spectrum. Simulation results are presented to show the improvements achieved by the proposed protocol. Cellular mobile radio networks commonly respond to an increase in the service demand by using smaller coverage areas. As a result, the volume of the signalling exchanges increases. In this research, a proposal for interconnecting the various entitles of the mobile radio network over the future broadband networks based on the IEEE 802.6 Metropolitan Area Network (MAN) is outlined. Simulation results are presented to show the benefits achieved by interconnecting these entities over the broadband Networks.

Cryptographic techniques for personal communication systems security

The advent of personal communication systems within the last decade has depended upon the utilization of advanced digital schemes for source and channel coding and for modulation. The inherent digital nature of the communications processing has allowed the convenient incorporation of cryptographic techniques to implement security in these communications systems. There are various security requirements, of both the service provider and the mobile subscriber, which may be provided for in a personal communications system. Such security provisions include the privacy of user data, the authentication of communicating parties, the provision for data integrity, and the provision for both location confidentiality and party anonymity. This thesis is concerned with an investigation of the private-key and public-key cryptographic techniques pertinent to the security requirements of personal communication systems and an analysis of the security provisions of Second-Generation personal communication systems is presented. Particular attention has been paid to the properties of the cryptographic protocols which have been employed in current Second-Generation systems. It has been found that certain security-related protocols implemented in the Second-Generation systems have specific weaknesses. A theoretical evaluation of these protocols has been performed using formal analysis techniques and certain assumptions made during the development of the systems are shown to contribute to the security weaknesses. Various attack scenarios which exploit these protocol weaknesses are presented. The Fiat-Sharmir zero-knowledge cryptosystem is presented as an example of how asymmetric algorithm cryptography may be employed as part of an improved security solution. Various modifications to this cryptosystem have been evaluated and their critical parameters are shown to be capable of being optimized to suit a particular applications. The implementation of such a system using current smart card technology has been evaluated.

Development and validaton of an indicator to compare antibiotic usage in secondary care in England

The use of antibiotics was investigated in twelve acute hospitals in England. Data was collected electronically and by questionnaire for the financial years 2001/2, 2002/3 and 2003/4. Hospitals were selected on the basis of their Medicines Management Self-Assessment Scores (MMAS) and included a cohort of three hospitals with integrated electronic prescribing systems. The total sample size was 6.65% of English NHS activity for 2001/2 based on Finished Consultant Episode (FCE) numbers. Data collected included all antibiotics dispensed (ATC category J01), hospital activity FCE's and beddays, Medicines Management Self-assessment scores, Antibiotic Medicines Management scores (AMS), Primary Care Trust (PCT) of origin of referral populations, PCT antibiotic prescribing rates, Index of Multiple Deprivation for each PCT. The DDD/FCE (Defined Daily Dose/FCE) was found to correlate with the DDD 100beddays (r = 0.74 p

Development of a computerised library system in the construction industry

This thesis examines the ways that libraries have employed computers to assist with housekeeping operations. It considers the relevance of such applications to company libraries in the construction industry, and describes more specifically the development of an integrated cataloguing and loan system. A review of the main features in the development of computerised ordering, cataloguing and circulation control systems shows that fully integrated packages are beginning to be completed, and that some libraries are introducing second generation programs. Cataloguing is the most common activity to be computerised, both at national and company level. Results from a sample of libraries in the construction industry suggest that the only computerised housekeeping system is at Taylor Woodrow. Most of the firms have access to an in-house computer, and some of the libraries, particularly those in firms of consulting engineers, might benefit from computerisation, but there are differing attitudes amongst the librarians towards the computer. A detailed study of the library at Taylor Woodrow resulted in a feasibility report covering all the areas of its activities. One of the main suggestions was the possible use of a computerised loans and cataloguing system. An integrated system to cover these two areas was programmed in Fortran and implemented. This new system provides certain benefits and saves staff time, but at the cost of time on the computer. Some improvements could be made by reprogramming, but it provides a general system for small technical libraries. A general equation comparing costs for manual and computerised operations is progressively simplified to a form where the annual saving from the computerised system is expressed in terms of staff and computer costs and the size of the library. This equation gives any library an indication of the savings or extra cost which would result from using the computerised system.

Optimizing rate algorithms in wireless networks

Since wireless network optimisations can be typically designed and evaluated independently of one another under the assumption that they can be applied jointly or independently. In this paper, we have analysis some rate algorithms in wireless networks. Since wireless networks have different standards in IEEE with peculiar features, data rate is one of those important parameters that wireless networks depend on for performances. The optimisation of this network is dependent on the behaviour of a particular rate algorithm in a network scenario. We have considered some first and second generation's rate algorithm, and it is all about selecting an appropriate data rate that any available wireless network can utilise for transmission in order to achieve a good performance. We have designed and analysis a wireless network and results obtained for some rate algorithms, like ONOE and AARF.