In the present work I study temperature dependence of magnetic penetration depth in superconductors which allows us to determine the symetry of the order parameter, important for theoretical models. In conventional superconductors we talk about s-symetry. Energy gap is isotropic and as a consequence of this fact penetration depth grows exponencialy with the temperature. On the other hand, in unconventional superconductors with d-symetry we find the power dependence on the temperature. Anyway the exponent depends on impurities and structure of the material and the influence of these parametrs is not completely clear at the moment.

In dieser Arbeit wurde zum einen die Penetration von Foamyviren (FV) unter besonderer Berücksichtung des FV Hüllglykoproteins (Env) untersucht, zum anderen wurden Adenovirus-Foamyvirus (Ad-FV) Hybridvektoren zur Kombination der Vorteile beider Vektorsysteme konstruiert und analysiert. Das Ziel war die Herstellung von Ad-FV Vektoren mit hohen Titern, die stabil in das Genom des Wirts integrieren. Über die Penetration von FV ist bisher wenig bekannt. Umhüllte Viren können entweder durch direkte Fusion der viralen Hülle mit der Zellmembran oder durch rezep-torvermittelte Endocytose, oft mit einem pH-abhängigen Fusionsschritt der viralen Membran mit der Membran intrazellulärer Kompartimente, in Zielzellen gelangen. In dieser Studie wurde die Abhängigkeit der FV Env vermittelten Infektion verschie-dener FV Spezies von lysosomotropen Agenzien mit MuLV oder Prototyp FV (PFV) Pseudotypen analysiert. Ähnlich wie bei Vesikuläres Stomatitis Virus Glykoprotein (VSV-G) Pseudotypen wurde die FV Env vermittelte Infektion von fast allen Agen-zien, die den endosomalen pH anheben, inhibiert. Allerdings hatte Chloroquin keine inhibitorische Wirkung auf die FV Env vermittelte Infektion im Gegensatz zu der VSV-G katalysierten, was auf einen unter-schiedlichen Penetrationsmechanismus schließen lässt. Eine Analyse der pH-Abhängigkeit der FV Env Fusionsaktivität in einem Zell-Fusionsassay zeigte eine Induktion der Fusionsaktivität mit einer maximalen Stärke bei pH 5,5. Nur bei PFV Env wurde eine basale Fusionsaktivität bei neutralem pH detektiert. Die relativ schnelle Induktion der Fusionsaktivität in saurem Milieu weist auf eine Konformationsänderung des Hüllglykoproteins zur Transformation in einen fusionsaktiven Status hin. Aufgrund dieser Daten kann man von einem endocytotischen, pH-abhängigen Penetrationsmechanismus von FV ausgehen. Zur Kombination der Vorteile von Adenoviren und FV wurde ein Ad-FV Hybridvektorsystem konstruiert um eine effizientes Werkzeug zum stabilen Gentransfer zu schaffen. Das System besteht aus adenoviralen Hochkapazitäts- (HC-Ad) Vektoren auf Adenovirus 5 Basis, die eine selbst-inaktivierende PFV Vektor Kassette unter Kontrolle eines humanen Cytomegalovirus- (hCMV) Promotors oder des reversen Tet Transaktivator Systems (Tet) enthalten. In alle Vektoren ist eine Verstärktes Grün Fluoreszierendes Protein (EGFP) Expressionskassette als Markergen integriert. Es wurden sowohl FV Vektoren, die nach der Primärinfektion über einen intrazellulären Transduktionsmechanismus stabil integrieren, als auch solche, die über einen Se-kundärzyklus mit Hilfe extrazellulärer Partikel stabil transduzieren können, hergestellt. Die Ad-FV Vektoren konnten mit zu herkömmlichen HC-Ad Vektoren vergleich-baren Titern bis zu 1010 iU/ml produziert werden. In Ad-FV infizierten Zellen war die erwartete FV Proteinexpression und ihre Induzierbarkeit bei Ad-FVTet Vektoren nachweisbar. Mit diesen Vektorsystemen infizierte Zellen zeigten eine signifikant höhere persistierende Transgenexpression im Vergleich zu mit HC-Ad oder Kontroll- Ad-FV Vektoren ohne ein funktionales FV pol ORF infizierten Zellen. Eine Southern Blot Analyse von Ad-FVTet infizierten Einzelzellklonen mit persistierender EGFP Expression belegte eine stabile Integration der FV Vektor Kassette. In dieser Arbeit konnten Ad-FV Vektoren mit hohem Titer hergestellt werden, die eine, auch im Vergleich mit bisher publizierten Ad-Retrovirus Systemen, stark erhöhte Effizienz des persistenten Transgentransfers durch stabile Integration zeigten. / In this study, both, the analysis of the penetration mechanism of Foamy Viruses (FV), focusing on the FV envelope glycoprotein (Env), and the construction and analysis of Adenovirus (Ad)-FV hybrid vectors for efficient prolonged transgene expression, was addressed. Little is known about the uptake of foamy viruses, a subfamily of retroviruses, into target cells. In general enveloped viruses use two different entry strategies, an endocytotic entry pathway, mostly involving a pH-dependent fusion process, and a pH-independent fusion process at the cell membrane. In this study, we examined the pH dependence of FV entry by analyzing FV Env mediated infectivity of target cells in the presence of weak bases, vacuolar ATPase inhibitors and carboxylic ionophores using Murine Leukemia Virus (MuLV) or FV vector pseudotypes. Similiar to Vesicular Stomatitis Virus glycoprotein G (VSV-G) mediated uptake, FV Env mediated entry was inhibited by most agents used. However, in contrast to VSV-G pseudotypes, chloroquine failed to reduce the infectivity of FV Env pseudotypes, implying that the pathway is different from that of VSV-G. Various glycoproteins from other FV species showed a similiar inhibition pattern as the prototype FV (PFV). Analysis of the pH-dependence of the FV mediated fusion process in a cell-to-cell fusion assay revealed an induction of syncitia formation by a short exposure to acidic pH, peaking around pH 5.5. The very short time period of exposure to low pH neccessary for the induction of fusion activity implies a conformational change of FV Env at low pH to transform to a fusogenic state. Interestingly, of all FV Env species analyzed only the PFV Env had a significant fusion activity a neutral pH. Taken together, these data suggest a pH-dependent endocytotic pathway of infection of target cells by FV. In this work, an adenoviral/foamyviral (Ad-FV) hybrid vector system was developed to exploit the favourable features of the two parental viral species for efficient and stable gene transfer. The system consists of high capacity (HC-Ad) Adenovirus 5 vectors containing self-inactivating PFV vector cassettes under control of a human cytomegalovirus- (hCMV) promotor or the reverse Tet transactivator system (Tet). The PFV Enhanced Green Fluorescent Protein (EGFP) transfer vectors encoded by this vector cassettes could either transduce target cells by an intracellular retrotransposition step or by an additional secondary cycle with extracellular paticles. The Ad-FV vectors could be produced with titers up to 1010 iU/ml, comparable to conventional Ad vectors. We were able to demonstrate the predicted pattern of PFV protein expression in Ad-FV vector infected cells and the induction of PFV protein expression in Ad-FVTet infected cells. Long-term analysis of cells infected by the chimeric vec-tors showed a significantly higher amount of persistent transgene expressing cells when compared to cells infected by a control vector containing a non-functional FV pol ORF or by a conventional HC-Ad vector. Southern blot analysis of persistently transgene expressing cells indicated stable integration of the PFV vector genome in cells infected by Ad-FVTet vectors. In summary, our results demonstrate the production of high titer Ad-FV hybrid vectors mediating, even compared to other published Ad-Retrovirus systems, prolonged transgene expression by stable integration.

Introdução: A barreira hematoencefálica limita a penetração de compostos farmacologicamente ativos para o cérebro devido à presença de zônulas de oclusão no endotélio cerebral e a expressão de transportadores de influxo e efluxo que modulam o acesso de fármacos para o parênquima cerebral. Nanocápsulas de núcleo lipídico (LNC) tem sido estudadas como carreadores de fármacos para o tecido cerebral devido à capacidade de modulação da farmacocinética desses compostos. Entretanto, ainda pouco se sabe sobre os processos envolvidos nas alterações farmacocinéticas e na distribuição tecidual promovidas por esses transportadores. Objetivo: Pretendeu-se investigar as alterações na farmacocinética plasmática e penetração cerebral da quetiapina (QTP) nanoencapsulada em ratos Wistar. Materiais e Métodos: QLNC (1mg/mL) foram obtidas através da metodologia de nanoprecipitação e apresentaram reduzido tamanho de partícula (143 ± 6 nm), baixo indicie de polidispersão (PI < 0.1), alta eficiência de encapsulação (96%), potencial zeta negativo (-7.65 ± 0.815 mV) e pH ácido. QLNC quando visualizadas por MET apresentaram tamanho esférico, homogêneo com ausência de agregados. Os estudos in vivo desse trabalho foram aprovados pelo CEUA/UFRGS. Análise do plasma total e a utilização da microdiálise para determinação das concentrações plasmáticas e cerebrais livres foram realizadas após administração intravenosa da formulação de nanocápsulas de QTP (5 mg /kg ) (QLCN) ou do fármaco em solução (FQ) (5 mg /kg e 10 mg /kg) na presença e na ausência de 30 mg /kg de probenecida (PB), um inibidor de transportadores de membrana. Métodos validados foram utilizados para a quantificação do fármaco em diferentes matrizes. As concentrações cerebral e hepática totais foram investigadas através da técnica de homogeneizado de tecido. Além disso, a fração livre no plasma (fu) e a penetração nos eritrócitos também foi realizada. Resultados: QTP apresentou farmacocinética linear na faixa de doses investigadas, é um substrato para transportadores de efluxo na BHE. Diferenças foram observadas na fu da QTP até 2 h após administração de QLNC indicando que LNC do tipo III promove uma liberação sustentada do fármaco do carreador. QLNC não foi capaz de alterar o coeficiente de partição nos eritrócitos determinado in vitro. As concentrações cerebrais e hepáticas totais foram aumentadas após administração da formulação de nanocápsulas, porém, as concentrações cerebrais livres não foram alteradas em comparação com o QTP em solução. Após administração de PB o fator de penetração da QTP livre no cérebro foi reduzido de 1,55 ± 0.17 para 0,94 ± 0,15. Porém, essa inibição pela probenecida não teve efeito na penetração cerebral de QLNC (0,88 ± 0,21 – 0,92 ± 0.13) provavelmente devido ao fato da QTP ser carreada pela LNC e não estar disponível para interagir com transportadores. Conclusão: Considerando todos os resultados sugere-se que as LNC do tipo III carreiam a QTP através da circulação sistêmica até o parênquima cerebral. / Introduction: Blood-brain barrier (BBB) hinders the delivery of therapeutics to central nervous system due to the endothelial cells tight junctions, which restrict paracellular transport of substances, and the expression of influx and efflux transporters, which modulate drugs access to the brain. Lipid-core nanocapsules (LNC) have been proposed as drug carriers to improve brain delivery by modulating drug pharmacokinetics (PK). However, little in know about this modulation process and it is not clear whether the LCN carry the drug through the BBB or increase free drug penetration due to changes in the barrier permeability. Objective: The work aimed to investigate the alterations in the model drug quetiapine (QTP) plasma PK and brain penetration following nanoencapsulation into LNC (QLNC) using microdialysis. Methods: QLNC (1 mg.mL-1) were obtained by nanoprecipitation and presented small particle size (143 ± 6 nm), low polidispersion index (PI < 0.1), high incorporation efficiency (96%), negative zeta potential (–7.65 ± 0.815 mV) and acidic pH. TEM photomicrography showed spherically shaped particles and absence of aggregation. Animal studies approved by CEUA/UFRGS. Total plasma and free plasma and brain concentrations, last two determined by microdialysis, were analyzed after QLNC (5 mg/kg) and free drug (FQ – 5 and 10 mg/gk) i.v. dosing to Wistar rats alone or following probenecid (PB), an influx transporter inhibitor, i.v. administration (30 mg/kg). Drug was quantified in all matrices by validate LC/UV methods. Total brain and liver concentration after FQ and QLNC dosing were investigated in tissues homogenate. Furthermore, QTP free fraction (fu) in plasma and erythrocyte penetration were determined. Results: QTP presented linear PK in the dose range investigated and is substrate to influx transporters at the BBB. Differences observed on QTP fu up to 2 h after QLNC dosing indicate a drug slow release in the blood stream loaded into the LNC type III nanocarrier for this period of time. The LNC did not altered QTP erythrocytes partition coefficient. Total brain and liver concentrations were increased after QLNC dosing but free brain concentrations were not altered in comparison with FQ dosing. After PB dosing, QTP brain penetration was reduced from 1.55 ± 0.17 to 0.94 ± 0.15 when FQ was administered but the inhibition of influx transporters had no effect on QLNC brain penetration (0.88 ± 0.21 to 0.92 ± 0.13) probably because QTP is loaded into the LNC and not available to interact with transporters. Conclusions: Taking together these results suggested that LNC type III carries QTP in the blood stream and delivers the drug to the brain.

This study looked at the effect relative humidity had on respirator performance.

Software as a Service (SaaS) is a modern software product model that provides an awesome experience and dynamic platform for the expedition, communication and creating new features in a short amount of time. Cloud platforms provide an outstanding foundation for Software as a solution with their on user-demand infrastructure and application service. We can say that microservice architecture as the optional architecture for a cloud-hosted solution. Microservice architecture is not that much build-up, it just started getting attraction from various industries who want to market for their product in a short time by expanding productivity through increasing automation in the whole product lifecycle[1]. Microservice architecture approach come-up with lots of new complexity and it need a certain level of maturity development to confidently apply the architectural style. The challenge we are facing is how do we make sure the system stays safe and doesn't get hacked or leak data in this more complex and versatile cloud environment. Hence, we need to do penetration testing on the newly developed application in a microservice architecture.

Concrete cylinder piles produced by a centrifugally cast, vibrated, roller compacted process have shown promising corrosion durability in marine environments. Three bridges in the Florida Panhandle with approximately 40 years of service in aggressive marine service were examined. A newly constructed marine bridge utilizing concrete cylinder piles was also examined to verify corrosion performance of piles manufactured with modern building materials and construction compared to piles built several decades ago. Survey of the marine bridges showed minimal corrosion distress despite low design concrete cover to steel hoop reinforcements (20-40 mm). Typical concrete distress included minor rust staining but not necessarily indicating corrosion of reinforcement steel. Thin longitudinal cracks were frequently observed but were likely caused by mechanical damage from pile driving rather than stemming from corrosion distress. Chloride ion diffusivity was low, in the order of 1x10-13 m2/s. Other measured parameters such as concrete resistivity, porosity, and water absorption indicate low permeability. Chloride analysis of cracked and uncracked concrete cores from the older bridges in this study did not show pronounced preferential chloride penetration. Chloride analysis from the contemporary marine bridge did show some preferential transport of chloride ions at shallow depths through cracks with further evidence of lower electrical resistivity indicating enhanced electrolyte transport. The pore water pH of concrete samples from the contemporary bridge was high despite the presence of pozzolanic materials suggesting that normal chloride threshold values may be valid.

Thesis (Ph.D. (Pharmacy))--North-West University, Potchefstroom Campus, 2008.

Consumption of toxic endophyte-infected (E+) tall fescue pastures is known to have a negative impact on bull reproductive performance. Since decreased cleavage rates of embryos fertilized with spermatozoa from bulls grazing E+ tall fescue pastures have been observed in several studies using differing sets of bulls, technicians, pastures, and other methods of inducing tall fescue toxicosis (ergotamine tartrate), it is hypothesized that spermatozoa function from bulls grazing E+ is impaired in ways undetectable by gross semen examination. During a three-month grazing study, 6 Angus bulls were utilized to determine the effects of grazing E+ tall fescue pastures on growth performance and spermatozoa function. Bulls were appointed to graze Kentucky 31 tall fescue (Festuca arundinacea Schreb.) infected with Neotyphodium coenophialum, an ergot alkaloid producing endophyte (n=3) or Jesup tall fescue infected with non-ergot alkaloid producing endophyte (NTE) MaxQTM (n=3). Bulls were grouped by body weight (BW) and scrotal circumference (SC) to graze pastures from April 18-June 26, 2007. Blood samples, BW, SC, semen, and rectal temperatures (RT) were collected every 7 d. Scrotal temperatures (ST) were obtained before semen collection each week in June. Semen was evaluated for gross motility, morphology, and Computer Assisted Semen Analysis (CASA) parameters. Semen from a subset of bulls (n=2 per treatment) was used to assess spermatozoa ability to function utilizing in vitro assays. Growth performance was decreased in E+ bulls compared to bulls grazing NTE tall fescue pastures (P = 0.002). Concentrations of prolactin were reduced in bulls grazing E+ compared to bulls grazing NTE tall fescue pastures (P = 0.055). Motility post-thaw and during a 3-hour stress test were decreased (P = 0.024 and P < 0.0001, respectively), in addition to altered CASA parameters for spermatozoa. Penetration was reduced in oocytes fertilized with spermatozoa from bulls grazing E+ (64.54 ± 3.28%) compared to NTE tall fescue pastures (87.42 ± 1.63%, P < 0.0001) coupled with hastened meiotic completion, and reduced intracellular calcium parameters. These findings indicate impaired spermatozoa function in bulls grazing E+ tall fescue pastures that extends beyond gross semen characteristics, and may provide direction for future studies.

No description available.

Penetration testing is widely used in industry as a test method for web application security assessment. However, penetration testing is often performed late in a software development life cycle as an isolated task and usually requires specialized security experts. There is no well-defined test framework providing guidance and support to general testers who usually do not have in-depth security expertise to perform a systematic and cost-efficient penetration test campaign throughout a security-oriented software development life cycle. In this thesis, we propose a model-driven penetration test framework for web applications that consists of a penetration test methodology, a grey-box test architecture, a web security knowledge base, a test campaign model, and a knowledge-based PenTest workbench. The test framework enables general testers to perform a penetration test campaign in a model-driven approach that is fully integrated into a security-oriented software development life cycle. Security experts are still required to build up and maintain a web security knowledgebase for test campaigns, but the general testers are capable of developing and executing penetration test campaigns with reduced complexity and increased reusability in a systematic and cost-efficient approach. A prototype of the framework has been implemented and applied to three web applications: the benchmark WebGoat web application, a hospital adverse event management system (AEMS), and a palliative pain and symptom management system (PAL-IS). An evaluation of the test framework prototype based on the case studies indicates the potential of the proposed test framework to improve how penetration test campaigns are performed and integrated into a security-oriented software development life cycle.