The Plasmodium serine-type SERA proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite

Parasite proteases play key roles in several fundamental steps of the Plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. Plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called 'serine repeat antigens' (SERAs). A SERA subfamily, represented by Plasmodium falciparum SERA5, contains an atypical active site serine residue instead of a catalytic cysteine. Members of this SERAser subfamily are abundantly expressed in asexual blood stages, rendering them attractive drug and vaccine targets. In this study, we show by antibody localization and in vivo fluorescent tagging with the red fluorescent protein mCherry that the two P. berghei serine-type family members, PbSERA1 and PbSERA2, display differential expression towards the final stages of merozoite formation. Via targeted gene replacement, we generated single and double gene knockouts of the P. berghei SERAser genes. These loss-of-function lines progressed normally through the parasite life cycle, suggesting a specialized, non-vital role for serine-type SERAs in vivo. Parasites lacking PbSERAser showed increased expression of the cysteine-type PbSERA3. Compensatory mechanisms between distinct SERA subfamilies may thus explain the absence of phenotypical defect in SERAser disruptants, and challenge the suitability to develop potent antimalarial drugs based on specific inhibitors of Plasmodium serine-type SERAs.

Electron microprobe results of clay minerals from samples of the Frankenwald and the Thüringer Wald

Late Devonian (Frasnian) pillow basalts from the Frankenwald and Thüringer Wald within the Saxothuringian zone in Germany were found to contain abundant putative biogenic filaments, indicating that the volcanic rocks once harbored microbial life. The mineralized filaments are found in calcite-filled amygdules (former vesicles), where they started to form on internal surfaces of vesicles after seawater ingress. The filaments postdate an early fibrous carbonate cement but predate later equant calcite spar, revealing syngenetic formation. A biogenic origin of filaments is indicated by their size and morphology resembling modern microorganisms, their independence of crystal faces and cleavage plans, complex branching patterns, and internal segmentation. The filamentous microorganisms represent cryptoendoliths that lived in structural cavities of the basalt. They became preserved upon microbial clay authigenesis similar to the encrustation of modern prokaryotes in iron-rich environments. Filaments consist of clay minerals with the endmember composition berthierine-chamosite and illite-glauconite. Based on the discovery of fossilized filamentous microorganisms in Late Devonian pillow basalts of the Saxothurigian zone that are similar to filaments previously found in Middle Devonian pillow basalts of the Rhenohercynian zone, it is apparent that cryptoendolithic life was more widespread than previously recognized. Structural cavities within seafloor basalt may thus represent a common, perhaps universal niche for life in the oceanic crust.

Mechanisms of B and T lymphocyte accumulation in tumor-draining lymph nodes

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

NMR imaging of the diffusion of water at 37 degrees C into poly(2-hydroxyethyl methacrylate) containing aspirin or vitamin B-12

The ingress of water into poly(2-hydroxyethyl methacrylate), PHEMA, loaded with either one of two model drugs, vitamin B-12 or aspirin, was studied at 37 degreesC using three-dimensional NMR imaging. PHEMA was loaded with 5 and 10 wt % of the drugs. From the imaging profiles, it was observed that incorporation of vitamin B-12 into PHEMA resulted in enhanced crack formation on sorption of water and the crack healing behind the diffusion front was slower than for PHEMA without added drug. This was accounted for by the anti-plasticization of PHEMA by vitamin B-12. Crack formation was inhibited in the P-HEMA-aspirin systems because of the plasticizing effect of the aspirin on the PHEMA matrix. All of the polymers were found to absorb water according to an underlying Fickian diffusion mechanism. For PHEMA loaded with 5 wt % of aspirin or vitamin B-12, the best values of the water diffusion coefficients were both found to be 1.3 +/- 0.1 x 10(-11) m(2) s(-1) at 37 degreesC, while the values for the polymer loaded with 10 wt % of the drugs were slightly higher, 1.5 +/- 0.1 x 10(-11) m(2) s(-1).

Mass uptake study of the diffusion of water and SBF into poly(2-hydroxyethyl methacrylate-co-tetrahydrofurfuryI methacrylate) containing aspirin or vitamin B-12

The ingress of water and Kokubo simulated body fluid (SBF) into poly (2-hydroxyethyl methacrylate) (PHEMA), and its co-polymers with tetrahydrofurduryl methacrylate (THFMA), loaded with either one of two model drugs, vitamin 1312 or aspirin, was studied by mass uptake over the temperature range 298-318 K. The polymers were studied as cylinders and were loaded with either 5 wt% or 10 wt% of the drugs. From DSC studies it was observed that vitamin B-12 behaved as a physical cross-linker restricting chain segmental mobility, and so had a small anti-plasticisation effect on PHEMA and the co-polymers rich in HEMA, but almost no effect on the T-g of co-polymers rich in THFMA. On the other hand, aspirin exhibited a plasticising effect on PHEMA and the copolymers. All of the polymers were found to absorb water and SBF according to a Fickian diffusion mechanism. The polymers were all found to swell to a greater extent in SBF than in water, which was attributed to the presence of Tris buffer in the SBF. The sorptions of the two penetrants were found to follow Fickian kinetics in all cases and the diffusion coefficients at 310 K for SBF were found to be smaller than those for water, except for the polymers containing aspirin where the diffusion coefficients were higher than for the other systems. For example, for sorption into PHEMA the diffusion coefficient for water was 1.41 X 10(-11) m(2)/s and for SBF was 0.79 x 10-11 m(2)/s, but in the presence of 5 wt% aspirin the corresponding values were 1.27 x 10(-1)1 m(2)/s and 1.25 x 10(-11) m(2)/s, respectively. The corresponding values for PHEMA loaded with 5 wt% B-12 were 1.25 x 10(-11) m(2)/s and 0.74 x 10(-11) m(2)/s, respectively.

Vitamin B-12 release from P(HEMA-co-THFMA) in water and SBF: A model drug release study

A model drug release study on the ingress of water and Kokubo simulated body fluid (SBF) into poly(2-hydroxyethyl methacrylate) (THFMA) and its copolymers with tetrahydrofurfuryl methacrylate (THFMA) loaded with vitamin B-12 was undertaken over the temperature range 298-318 K. The polymers were studied as cylinders and were loaded with either 5 or 10 wt-% of the drug. The drug release from the polymers was found to follow a Fickian diffusion mechanism in the early stages of the drug release, with higher normalized release rates at higher temperatures and higher drug loadings. The normalized release rates were also found to be higher for the SBF solution than for water. The copolymer composition was found to have a significant effect on the rate of release of the drug, with the rate falling rapidly between HEMA mole fractions of 1.0 and 0.8, but for lower mole fractions of HEMA the normalized release rate decreased more slowly. This behaviour followed the trend found for the changes in the equilibrium penetrant contents for the copolymers.

NMR imaging of the diffusion of water at 310 K into poly[(2-hydroxyethyl methacrylate)-co-(tetrahydrofurfuryl methacrylate)] containing vitamin B12 or aspirin

The ingress of water into copolymers of 2-hydroxyethyl methacrylate (HEMA) and tetrahydrofurfuryl methacrylate (THFMA) loaded with either one of two model drugs, ie vitamin B-12 or aspirin, was studied at 310 K using three-dimensional nuclear magnetic resonance (3D NMR) imaging. The poly(HEMA) was loaded with 5 wt% of the drugs. From the imaging profiles it was observed that incorporation of vitamin B-12 into the polymers rich in HEMA resulted in crack formation at the interface between the rubbery region and the glassy core on sorption of water, although these cracks were 'healed' behind the diffusion front. However, for the copolymers with low HEMA contents and for those containing aspirin, no evidence for similar crack formation was found. For the copolymers loaded with 5 wt% of aspirin or vitamin B-12 the values of the water diffusion coefficients, determined by curve-fitting the relative water concentration profiles from magnetic resonance imaging (MRI) measurements, were found to be smaller than those obtained from a mass uptake study. (C) 2004 Society of Chemical Industry.

Bajo de la Alumbrera copper-gold deposit: Stable isotope evidence for a porphyry-related hydrothermal system dominated by magmatic aqueous fluids

Alteration zones at the gold-rich Bajo de la Alumbrera porphyry copper deposit in northwestern Argentina are centered on several porphyritic intrusions. They are zoned from a central copper-iron sulfide and gold-mineralized potassic (biotite-K-feldspar +/- quartz) core outward to propylitic (chlorite-illite-epidote-calcite) assemblages. A mineralized intermediate argillic alteration assemblage (chlorite-illite +/- pyrite) has overprinted the potassic alteration zone across the top and sides of the deposit and is itself zoned outward into phyllic (quartzinuscovite-illite +/- pyrite) alteration. This study contributes new data to previously reported delta(18)O and delta D compositions of fluids responsible for the alteration at Bajo de la Alumbrera, and the data are used to infer likely ore-forming processes. Measured and calculated delta(18)O and delta D values of fluids (+8.3 to +10.2 and -33 to -81 parts per thousand, respectively) confirm a primary magmatic origin for the earliest potassic alteration phase. Lower temperature potassic alteration formed from magmatic fluids with lower delta D values (down to -123 parts per thousand). These depleted compositions are distinct from meteoric water and consistent with degassing and volatile exsolution of magmatic fluids derived from an underlying magma. Variability in the calculated composition of fluid associated with potassic alteration is explained in terms of phase separation (or boiling). if copper-iron sulfide deposition occurred during cooling (as proposed elsewhere), this cooling was largely a result of phase separation. Magmatic water was directly involved in the formation of overprinting intermediate argillic alteration assemblages at Bajo de la Alumbrera. Calculated delta(18)O and delta D values of fluids associated with this alteration range from +4.8 to +8.1 and -31 to -71 per mil, respectively Compositions determined for fluids associated with phyllic alteration (-0.8 to +10.2 and -31 to -119 parts per thousand) overlap with the values determined for the intermediate argillic alteration. We infer that phyllic alteration assemblages developed during two stages; the first was a high-temperature (400 degrees-300 degrees C) stage with D-depleted water (delta D = -66 to -119 parts per thousand). This compositional range may have resulted from magma degassing and/or the injection of new magmatic water into a compositionally evolved hydrothermal system. The isotopic variations also can be explained by increased fluid-rock interaction. The second stage of phyllic alteration occurred at a lower temperature (similar to 200 degrees C), and variations in the modeled isotopic compositions imply mixing of magmatic and meteoric waters. Ore deposition that occurred late in the evolution of the hydrothermal system was probably associated with further cooling of the magmatic fluid, in part caused by fluid-rock interaction and phase separation. Changing pH and/or oxygen fuoracity may have caused additional ore deposition. The ingress of meteoric water appears to postdate the bulk of mineralization and occurred as the system at Bajo de la Alumbrera waned.

Injuries associated with continuous miners, shuttle cars, load-haul-dump and personnel transport in New South Wales underground coal mines

In the three years to June 2005, 959 injuries associated with continuous miners (CMs), shuttle cars (SCs), load–haul–dump and personnel transport (PT) were reported by NSW underground coal mines, comprising 23% of all injuries reported. The present paper reports an analysis of the narrative field accompanying these reports to determine opportunities for controlling injury risks. The most common combinations of activity and mechanism were: strain while handling CM cable (96 injuries); caught between or struck by moving parts while bolting on a CM (86 injuries); strains while bolting on CM (54 injuries); and slipping off a CM during access, egress or other activity (60 injuries). For the other equipment considered, the common injury mechanism was the vehicle running over a pothole or other roadway abnormality causing the driver or passengers to be injured (169 injuries). Potential control measures include: monorails for CM services; hydraulic cable reelers; handrails on CM platforms; redesign of CM platforms and bolting rigs to reduce reach distances during drilling and bolting; improvements to guarding of bolting controls; standardisation and shape coding of bolting controls; two handed fast feed; improvements in underground roadway maintenance, vehicle suspension, visibility and seating; and pedestrian proximity warning devices.

ENSINO DE SUSTENTABILIDADE NO CURSO DE ADMINISTRAÇÃO: A PERSPECTIVA DO EGRESSO

O objetivo desse trabalho foi investigar a contribuição do curso de Administração na formação de uma visão sistêmica das relações sociais, econômicas e ambientais dos seus egressos na visão dos mesmos. A tomada de decisões no ambiente corporativo requer que se considerem os interesses sociais e ambientais, além do econômico; devido, em particular, à atual crise civilizatória em que vivemos. A metodologia utilizada é a qualitativa, por meio da pesquisa exploratória, bibliográfica e de campo. O trabalho buscou aliar o suporte teórico, por meio das contribuições de Elkington (1994), Sachs (2006), Porrit (2007), Aligleri (2009), Barbierri (2010), Fazenda (2001,2008) Freire (1981,1987,1996), Leff (2009), Leonard (1997), Kleiton (2012), Tilbury e Wortman (2004), Freeman (1984), Savage (1991), Mitchell (1997), Katz (1990), Martinelli (1997), ao campo empírico, tendo sido aplicadas entrevistas em profundidade com egressos do curso bacharelado em Administração que cursaram a disciplina de sustentabilidade. De acordo com a pesquisa realizada, identificou-se que os egressos não consideram que a disciplina de sustentabilidade tenha contribuído para o desenvolvimento de competências profissionais significativas para um administrador com uma visão sistêmica, entretanto quando o tema foi abordado de forma interdisciplinar houve maior aproveitamento por parte dos egressos.

CONTRIBUIÇÃO DOS CURSOS SUPERIORES DE TECNOLOGIA NA EDUCAÇÃO PROFISSIONAL DO TRABALHADOR BRASILEIRO

Os Cursos Superiores de Tecnologia são um tipo específico de graduação (tecnólogo), com características próprias, entre as quais, a focalização na especialização dos seus currículos e duração mais curta objetivando uma formação mais rápida. A graduação tecnológica vem sendo amplamente difundida no país desde a segunda metade da década de 1990, após a promulgação da lei no 9.394/96 LDB, e por uma série de decretos, portarias e pareceres do MEC/CNE. Entre as principais metas e objetivos do PNE para a educação superior, se destacam: diversificação do sistema superior de ensino para atender clientelas com demandas específicas de formação; articulação entre currículo e mercado de trabalho; financiamento e gestão; criação de políticas de acesso à educação superior que facilitem o ingresso de alunos provenientes de grupos de maior vulnerabilidade educacional; crescimento da oferta de educação superior para a faixa etária de 18 a 24 anos. O presente estudo tem por objetivo refletir e debater a contribuição dos CSTs na educação profissional do trabalhador brasileiro dentro das perspectivas do PNE. O estudo se fundamenta no método qualitativo, com base numa pesquisa exploratória e descritiva, caracterizada como estudo de caso único, através da pesquisa de campo realizada com alunos em formação e com egressos do Curso de Eletrônica Industrial da Faculdade de Tecnologia Senai Anchieta, na cidade de São Paulo. Para alcançar seus objetivos, o estudo foi dividido em duas etapas: a primeira faz uma análise das variáveis que caracterizam o perfil do aluno em formação buscando identificar sua percepção quanto à escolha pelo CST, conhecimento sobre essa modalidade de ensino e as expectativas futuras da profissão. Na segunda parte, o estudo faz uma análise da percepção do egresso acerca das habilidades e competências adquiridas durante a formação, o grau de satisfação com salário e plano de carreira, e a aceitação profissional do tecnólogo pelo mercado de trabalho. No estudo realizado com alunos em formação constatou-se que os índices de evasão escolar das primeiras turmas do curso foram elevados, sendo apontadas como principais causas as dificuldades de conciliação entre o horário de estudo com a do trabalho e as dificuldades econômicas familiares. O perfil do aluno em formação na IES em estudo é majoritariamente da faixa etária entre 18 e 24 anos; do gênero masculino; egresso do ensino médio feito em escola pública; morador em bairro periférico e natural de cidade da RMSP; o próprio aluno é responsável pelo pagamento das mensalidades; não houve interferência de terceiros na sua escolha pelo CST; tem percepção favorável quanto à empregabilidade futura como tecnólogo. A pesquisa com egressos apontou que os mesmos tem percepção favorável quanto à formação profissional recebida, exceto o fato de não terem atendido disciplinas que desenvolvessem competências gerenciais e de negócios; quanto à empregabilidade e perspectivas de carreira mostraram preocupação na valorização profissional do tecnólogo pelo mercado de trabalho; declararam estar insatisfeitos quanto ao salário recebido; quanto à educação continuada reconheceram ser esse o processo que os manterão atualizados profissionalmente. Como conclusão da pesquisa, há recomendação para estudos futuros na sondagem de outras possíveis causas da evasão escolar com alunos dos cursos com outros eixos temáticos e de IES públicas. Igualmente, aponta-se para a necessidade da proposta curricular da IES em estudo oferecer, além das disciplinas técnicas, outras que desenvolvam competências e habilidade em gestão de pessoas e negócios.

CAPACITAÇÃO DOCENTE PARA EAD Um estudo sobre a capacitação que o docente do ensino superior recebe para atuar na educação a distância.

No Ensino Superior, uma das discussões atuais é o oferecimento de cursos de graduação e pós-graduação na modalidade a distância. Diante da presente discussão que ocorre em torno da Educação a Distância - EAD, o presente trabalho teve como objetivo identificar a capacitação que o docente que elabora e ministra a aula, recebe pela Instituição na qual atua, tendo em vista que é um dos principais atores deste cenário. A pesquisa bibliográfica e documental, mostrou o cenário atual da Educação a Distância, a regulamentação vigente e principalmente, as posições favoráveis e contrárias dessa discussão. É notório que mesmo enfrentando dificuldades, a Educação a Distância tem mostrado um crescimento vertiginoso nos últimos anos. Seja no número de cursos oferecidos, ou no número de alunos matriculados, a Educação a Distância tem tomado espaço no Ensino Superior. O foco desta pesquisa é o docente que atua na EAD e para investigar a capacitação que esse docente recebe, no segundo momento da pesquisa, foram propostos questionários aos docentes que atuam na EAD e entrevistas com os profissionais que elaboram e planejam a capacitação para esses docentes. A partir dos questionários respondidos realizei uma análise sobre os aspectos considerados essenciais pelos docentes. Esta análise priorizou os aspectos definidos de onde emergiram categorias que propiciaram, juntamente com a interpretação das entrevistas, desenhar a capacitação que é realizada. Foi interessante observar que as duas Instituições participantes da pesquisa tem obtido grande sucesso no desenvolvimento de seus programas, uma vez que as pesquisas realizadas as apontam como bem avaliadas por seus alunos. São Instituições com filosofias e estruturas diferentes, com projetos pedagógicos baseados em pressupostos teóricos distintos, mas com modelos de Educação a Distância semelhantes. Como resultado desta pesquisa, observei que a maneira de planejar a capacitação dos docentes, acompanha a filosofia e o modo de pensar de cada uma das Instituições. Tenho ciência que muito ainda há de ser feito na educação em nosso país, mas o oferecimento de cursos de graduação, na modalidade a distância já mostra uma evolução e a capacitação, alinhada com os pressupostos que permeiam o projeto pedagógico, contribui para a qualidade da formação do egresso dessa modalidade.

Microstructural analysis of surface and interface zones in concrete

Several of OPC paste and concrete specimens, with different mix proportions, were cast against CPF and impermeable formwork (IF) and the profiles of pore structure, microhardness and scratch hardness of the cover zone were established. The chloride ingress and the depth of carbonation of the surface zone of concrete cast against CPF and IF were investigated. The main mechanisms controlling the ECR processes and the factors affecting such treatment were critically reviewed. Subsequently, as a means of restoring passivation of steel embedded in carbonated concrete, such HCP specimens were subjected to ECR. The influence of ECR on the chemistry of the pore solution and the microstructure of the surface and the steel/cement past interface zones were also studied. The main findings of this investigation were as follows: (a) The thickness of the microstructure gradient of cover concrete is significantly decreased with increasing period of water curing but is relatively unaffected by curing temperature, w/e ratio and the use of cement replacement materials. (b) The scratch hardness technique was shown to be potentially useful for characterising the microstructure and microhardness gradients of the surface zone. (c) A relationship between the microstructure gradient and mass transport properties of the surface zone was established. (d) The use of CPF resulted in a significant reduction in porosity of both the cement paste matrix and the aggregate/cement paste transition zone, and a marked improvement in the resistance of the surface zone to carbonation and the ingress of chloride ions. (e) The ECR treatment resulted in a marked densification of the pore structure and in changes to the pore solution chemistry and the cement phases of near-surface and steel/cement paste transition zones. This effect was more pronounced with current density, period of treatment and particularly with the use of sodium phosphate as an electrolyte.

Chloride resistance and durability of cement paste and concrete containing metakaolin

Metakaolin (MK), a calcined clay, was included as a partial cement replacement material, at up to 20% by weight of binder, in cement pastes and concrete, and its influence on the resistance to chloride ingress investigated. Reductions in effective chloride diffusion coefficients through hardened cement paste were obtained for binary blends and by combining OPC, MK and a second cement replacement material of pulverised fuel ash or ground granulated blast furnace slag. Steady state oxygen diffusion measurements through hardened cement pastes measured using an electrochemical cell showed that the interaction between charged species and the pore surfaces is a major factor in determining chloride diffusion rate. Rheology of the binder, particularly at high MK replacement levels, was found to have a dramatic influence on the diffusion performance of cement pastes. It was concluded that plasticising admixtures are essential for adequate dispersion of MK in cement pastes. Chloride concentration profile analysis of the concrete cylinders, exposed to sodium chloride solution for one year, was employed to obtain apparent chloride diffusion coefficients for concrete specimens. MK was found to reduce the depth of chloride penetration into concrete when compared with that of unblended mixes. Corrosion rate and corrosion potential measurements were taken on steel bars embedded in concrete exposed to a saline environment under conditions of cyclic wetting and drying. The initiation time for corrosion was found to be significantly longer for MK blended mixes than for plain OPC systems. The aggregate-paste interfacial zone of MK blended systems was investigated by steady state diffusion of chloride ions through mortar containing glass beads as model aggregate. For the model aggregate specimens tested the work confirmed the hypothesis that properties of the bulk paste are the controlling factors in ionic diffusion through mortar.

Inorganic surface treatments for concrete protection

Carbonated cement paste surfaces were characterised prior to application of surface treatments. Their chemical and physical properties varied with distance from the surface and method of carbonation. From the surface inwards the pH of expressed pore solutions and porosity were observed to increase. Hardness increased after natural carbonation, but decreased after accelerated carbonation. Generally, accelerated carbonation caused more extreme changes. Investigations were carried out on four concrete surface hardening treatments; two sodium silicates and two silicofluorides. These treatments penetrated and hardened the surface of naturally dried uncarbonated cement paste to a depth fo 250m. Silicofluorides reacted with uncarbonated and carbonated cement pastes to form calcium fluoride. The question of how sodium silicates harden the surface remains unanswered. Surface hardeners do not significantly affect the rate of carbonation, and are unsuitable for re-alkalising carbonated cement paste. Water repellent treatments studied include a silane, a siloxane and a silicone. The silane exhibited the maximum penetration, up to 24mm under favourable conditions, but penetration in all cases was limited by moisture in the substrate. Water repellent treatments slow down water vapour diffusion but, with time, internal moisture levels should reflect external relative humidities. Water repellents may be used to reduce carbonation-induced corrosion where ingress of moisture from intermittent wetting may be slowed. However, treatment with water repellents can temporarily push the carbonation front deeper into the concrete.