Strontium chemistry of anhydrite from DSDP/ODP Hole 504B

A unique record of the chemical evolution of seawater during hydrothermal recharge into oceanic crust is preserved by anhydrite from the volcanic sequences and sheeted dike complex in ODP Hole 504B. Chemical and isotopic analyses 87Sr/86Sr, delta18O, delta34S of anhydrite constrain the changing composition of fluids due to reaction with basalt. There is a general trend of decreasing 87Sr/86Sr of anhydrite, corresponding to the minor incorporation of basaltic strontium with depth in the volcanic rocks. 87Sr/86Sr ratios decrease rapidly with depth in the dikes to values identical to host basalt (0.7029). Sr/Ca ratios (<0.1 mmol/mol) suggest that recharge fluids have very low Sr concentrations and fluids evolve by first precipitating Sr-bearing phases before extensive exchange of Sr with the host basalt. There is a background trend of decreasing sulfate delta18O with depth from +12-13? in the lower volcanics to +7? in the lower sheeted dikes recording an increase in recharge fluid temperature from c. 150° to c. 250°C, and confirming the presence of sulfate in hydrothermal fluids at elevated temperatures. From the amount of anhydrite recovered from Hole 504B and the amount of seawater sulfur that has been reduced to sulfide, a minimum seawater recharge flux can be calculated. This value is 4-25 times lower than estimates of high-temperature fluid fluxes based on either thermal constraints or global chemical budgets and suggests that there is significant deficit of seawater-derived sulfur in the oceanic crust. Only a minor proportion of the seawater that percolates into the crust near the axis is heated to high temperatures and exits as black smoker-type fluids. A significant proportion of the axial heat loss must be advected at 200-250°C by sulfate-bearing hydrothermal solutions that egress diffusely from the crust. These fluids penetrate into the dikes and exchange both heat and chemical tracers without the extensive clogging of porosity by anhydrite precipitation, which would halt hydrothermal circulation for any reasonable fluid flux. The heating of the major proportion of hydrothermal fluids to only moderate temperatures (c. 250°C) reconciles estimates of hydrothermal fluxes derived from thermal models and global geochemical budgets. The flux of hydrothermal sulfate would be of a magnitude similar to the riverine input, and oxygen-isotopic exchange at 200-250°C between dissolved sulfate and recharge fluids during hydrothermal circulation provides a mechanism to continuously buffer seawater sulfate oxygen to the light isotopic composition observed.

Strategies for Minimum Distance in Simulated Evacuation of Transport Airplanes

The present paper describes the preliminary stages of the development of a new, comprehensive model conceived to simulate the evacuation of transport airplanes in certification studies. Two previous steps were devoted to implementing an efficient procedure to define the whole geometry of the cabin, and setting up an algorithm for assigning seats to available exits. Now, to clarify the role of the cabin arrangement in the evacuation process, the paper addresses the influence of several restrictions on the seat-to-exit assignment algorithm, maintaining a purely geometrical approach for consistency. Four situations are considered: first, an assignment method without limitations to search the minimum for the total distance run by all passengers along their escaping paths; second, a protocol that restricts the number of evacuees through each exit according to updated FAR 25 capacity; third, a procedure which tends to the best proportional sharing among exits but obliges to each passenger to egress through the nearest fore or rear exits; and fourth, a scenario which includes both restrictions. The four assignment strategies are applied to turboprops, and narrow body and wide body jets. Seat to exit distance and number of evacuees per exit are the main output variables. The results show the influence of airplane size and the impact of non-symmetries and inappropriate matching between size and longitudinal location of exits.

Método de cálculo para la asignación de ocupantes a los elementos de evacuación de un edificio bajo la hipótesis de bloqueo (según CTE DB-SI3)

El buen dimensionado de los elementos de evacuación de los edificios es fundamental para conseguir una evacuación segura de los ocupantes en un evento accidental de fuego. Para ello es necesario conocer previamente la asignación de personas que previsiblemente los van a utilizar en caso de emergencia. En el presente trabajo de investigación, se desarrolla un método de cálculo que permite abarcar todos los escenarios posibles de bloqueos en caso de incendio permitiendo así conocer de antemano las distribuciones de personas en las vías de evacuación de manera conservadora. Dicho método de cálculo es aplicable tanto la justificación del cumplimiento de CTE DB-SI3, como en cualquier reglamentación internacional de protección contra incendios. ABSTRACT A good dimensioning of egress and elements of evacuation in buildings is essential for a safe evacuation of occupants in event of accidental fire. This requires prior knowledge of allocated number of people that will use them in an emergency. In this research, a calculation method is developed to cover every possible scenario of unavailable exit in case of fire, thereby allowing to know in advance the distributions of people on the escape routes and conservatively. This calculation method is applicable to both the confirmation of compliance with Spanish regulations, as in any international fire code.

CURSOS SUPERIORES DE TECNOLOGIA NO GRANDE ABC PAULISTA: PERCEPÇÃO DOS ALUNOS E PROFESSORES

Esta dissertação trata das percepções dos alunos, dos professores e do mercado de trabalho sobre os cursos superiores de tecnologia na região do grande ABC paulista, com a indicação histórica desta formação profissional. Através da análise de fatos que levaram à concepção desta modalidade de ensino e de como ela se integrou na sociedade brasileira atual, representada pela região do grande ABC paulista e do questionamento sócio, cultural e econômico de alunos que estão matriculados em uma instituição de ensino nela situada, bem como a análise das entrevistas realizadas com discentes, docentes e representantes do mercado de trabalho foi possível estabelecer o perfil de ingresso e de egresso destes alunos, uma vez que estão indicados todos os mecanismos possíveis para o percurso estabelecido por esta formação.(AU)

CURSOS SUPERIORES DE TECNOLOGIA NO GRANDE ABC PAULISTA: PERCEPÇÃO DOS ALUNOS E PROFESSORES

Esta dissertação trata das percepções dos alunos, dos professores e do mercado de trabalho sobre os cursos superiores de tecnologia na região do grande ABC paulista, com a indicação histórica desta formação profissional. Através da análise de fatos que levaram à concepção desta modalidade de ensino e de como ela se integrou na sociedade brasileira atual, representada pela região do grande ABC paulista e do questionamento sócio, cultural e econômico de alunos que estão matriculados em uma instituição de ensino nela situada, bem como a análise das entrevistas realizadas com discentes, docentes e representantes do mercado de trabalho foi possível estabelecer o perfil de ingresso e de egresso destes alunos, uma vez que estão indicados todos os mecanismos possíveis para o percurso estabelecido por esta formação.(AU)

Delayed loss of cholesterol from a localized lipoprotein depot in apolipoprotein A-I-deficient mice

The anti-atherogenic role of high density lipoprotein is well known even though the mechanism has not been established. In this study, we have used a novel model system to test whether removal of lipoprotein cholesterol from a localized depot will be affected by apolipoprotein A-I (apo A-I) deficiency. We compared the egress of cholesterol injected in the form of cationized low density lipoprotein into the rectus femoris muscle of apo A-I K-O and control mice. When the injected lipoprotein had been labeled with [3H]cholesterol, the t½ of labeled cholesterol loss from the muscle was about 4 days in controls and more than 7 days in apo A-I K-O mice. The loss of cholesterol mass had an initial slow (about 4 days) and a later more rapid component; after day 4, the disappearance curves for apo A-I K-O and controls began to diverge, and by day 7, the loss of injected cholesterol was significantly slower in apo A-I K-O than in controls. The injected lipoprotein cholesterol is about 70% in esterified form and undergoes hydrolysis, which by day 4 was similar in control and apo A-I K-O mice. The efflux potential of serum from control and apo A-I K-O mice was studied using media containing 2% native or delipidated serum. A significantly lower efflux of [3H]cholesterol from macrophages was found with native and delipidated serum from apo A-I K-O mice. In conclusion, these findings show that lack of apo A-I results in a delay in cholesterol loss from a localized depot in vivo and from macrophages in culture. These results provide support for the thesis that anti-atherogenicity of high density lipoprotein is related in part to its role in cholesterol removal.

Functional dynamics in the active site of the ribonuclease binase

Binase, a member of a family of microbial guanyl-specific ribonucleases, catalyzes the endonucleotic cleavage of single-stranded RNA. It shares 82% amino acid identity with the well-studied protein barnase. We used NMR spectroscopy to study the millisecond dynamics of this small enzyme, using several methods including the measurement of residual dipolar couplings in solution. Our data show that the active site of binase is flanked by loops that are flexible at the 300-μs time scale. One of the catalytic residues, His-101, is located on such a flexible loop. In contrast, the other catalytic residue, Glu-72, is located on a β-sheet, and is static. The residues Phe-55, part of the guanine base recognition site, and Tyr-102, stabilizing the base, are the most dynamic. Our findings suggest that binase possesses an active site that has a well-defined bottom, but which has sides that are flexible to facilitate substrate access/egress, and to deliver one of the catalytic residues. The motion in these loops does not change on complexation with the inhibitor d(CGAG) and compares well with the maximum kcat (1,500 s−1) of these ribonucleases. This observation indicates that the NMR-measured loop motions reflect the opening necessary for product release, which is apparently rate limiting for the overall turnover.

Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains.

The human cytomegalovirus (HCMV) early glycoprotein products of the US11 and US2 open reading frames cause increased turnover of major histocompatibility complex (MHC) class I heavy chains. Since US2 is homologous to another HCMV gene (US3), we hypothesized that the US3 gene product also may affect MHC class I expression. In cells constitutively expressing the HCMV US3 gene, MHC class I heavy chains formed a stable complex with beta 2-microglobulin. However, maturation of the N-linked glycan of MHC class I heavy chains was impaired in US3+ cells. The glycoprotein product of US3 (gpUS3) occurs mostly in a high-mannose form and coimmunoprecipitates with beta 2-microglobulin associated class I heavy chains. Mature class I molecules were detected at steady state on the surface of US3+ cells, as in control cells. Substantial perinuclear accumulation of heavy chains was observed in US3+ cells. The data suggest that gpUS3 impairs egress of MHC class I heavy chains from the endoplasmic reticulum.

Proteolysis of major histocompatibility complex class II-associated invariant chain is regulated by the alternatively spliced gene product, p41.

Invariant chain (Ii) is an intracellular type II transmembrane glycoprotein that is associated with major histocompatibility complex class II molecules during biosynthesis. Ii exists in two alternatively spliced forms, p31 and p41. Both p31 and p41 facilitate folding of class II molecules, promote egress from the endoplasmic reticulum, prevent premature peptide binding, and enhance localization to proteolytic endosomal compartments that are thought to be the sites for Ii degradation, antigen processing, and class II-peptide association. In spite of the dramatic and apparently equivalent effects that p31 and p41 have on class II biosynthesis, the ability of invariant chain to enhance antigen presentation to T cells is mostly restricted to p41. Here we show that degradation of Ii leads to the generation of a 12-kDa amino-terminal fragment that in p41-positive, but not in p31-positive, cells remains associated with class II molecules for an extended time. Interestingly, we find that coexpression of the two isoforms results in a change in the pattern of p31 degradation such that endosomal processing of p31 also leads to extended association of a similar 12-kDa fragment with class II molecules. These data raise the possibility that p41 may have the ability to impart its pattern of proteolytic processing on p31 molecules expressed in the same cells. This would enable a small number of p41 molecules to modify the post-translational transport and/or processing of an entire cohort of class II-Ii complexes in a manner that could account for the unique ability of p41 to enhance antigen presentation.

Sobre a evasão estudantil na Escola Politécnica da Universidade de São Paulo: identificação e possíveis causas.

A evasão estudantil afeta as universidades, privadas e públicas, no Brasil, trazendo-lhes prejuízos financeiros proporcionais à incidência, respectivamente, de 12% e de 26% no âmbito nacional e de 23% na Universidade de São Paulo (USP), razão pela qual se deve compreender as variáveis que governam o comportamento. Neste contexto, a pesquisa apresenta os prejuízos causados pela evasão e a importância de pesquisá-la na Escola Politécnica da USP (EPUSP): seção 1, desenvolve revisão bibliográfica sobre as causas da evasão (seção 2) e propõe métodos para obter as taxas de evasão a partir dos bancos de dados do Governo Federal e da USP (seção 3). Os resultados estão na seção 4. Para inferir sobre as causas da evasão na EPUSP, analisaram-se bancos de dados que, descritos e tratados na seção 5.1, contêm informações (P. Ex.: tipo de ingresso e egresso, tempo de permanência e histórico escolar) de 16.664 alunos ingressantes entre 1.970 e 2.000, bem como se propuseram modelos estatísticos e se detalharam os conceitos dos testes de hipóteses 2 e t-student (seção 5.2) utilizados na pesquisa. As estatísticas descritivas mostram que a EPUSP sofre 15% de evasão (com maior incidência no 2º ano: 24,65%), que os evadidos permanecem matriculados por 3,8 anos, que a probabilidade de evadir cresce após 6º ano e que as álgebras e os cálculos são disciplinas reprovadoras no 1º ano (seção 5.3). As estatísticas inferenciais demonstraram relação entre a evasão - modo de ingresso na EPUSP e evasão - reprovação nas disciplinas do 1º ano da EPUSP, resultados que, combinados com as estatísticas descritivas, permitiram apontar o déficit vocacional, a falta de persistência, a falta de ambientação à EPUSP e as deficiências na formação predecessora como variáveis responsáveis pela evasão (seção 5.4).

The accretion environment in Vela X-1 during a flaring period using XMM-Newton

We present analysis of 100 ks contiguous XMM-Newton data of the prototypical wind accretor Vela X-1. The observation covered eclipse egress between orbital phases 0.134 and 0.265, during which a giant flare took place, enabling us to study the spectral properties both outside and during the flare. This giant flare with a peak luminosity of 3.92+0.42-0.09 × 1037 erg s-1 allows estimates of the physical parameters of the accreted structure with a mass of ~1021 g. We have been able to model several contributions to the observed spectrum with a phenomenological model formed by three absorbed power laws plus three emission lines. After analysing the variations with orbital phase of the column density of each component, as well as those in the Fe and Ni fluorescence lines, we provide a physical interpretation for each spectral component. Meanwhile, the first two components are two aspects of the principal accretion component from the surface of the neutron star, the third component seems to be the X-ray light echo formed in the stellar wind of the companion.

Investigating the thymopoiesis stimulating property of interleukin-21 in aging mice

La vaccination est largement utilisée pour la génération de lymphocytes T spécifiques contre les tumeurs. Malheureusement, cette stratégie n'est pas adaptée aux personnes âgées car leur thymus régresse avec l'âge conduisant ainsi à une baisse dans la production de cellules T et à l'accumulation de cellules immunitaires âgées ayant des défauts liés à leurs stimulations. Comme il a été démontré auparavant que L’IL-21 est capable d’induire des fonctions thymiques, nous avons émis l’hypothèse que l’injection d’IL-21 à des souris âgées stimulera la thymopoïèse. Nos résultats montrent que l’administration de l’IL-21 augmente le nombre absolu de thymocytes chez les souris âgées et augmente la migration de ces cellules vers la périphérie ou ils contribuent à la diversité du TCR. De plus les cellules T en périphérie expriment un niveau plus élevé de miR181-a, et par conséquent moins de phosphatase comme SHP2, DUSP5/6 qui inhibent le TCR. En vaccinant des souris âgées avec le peptide Trp2, les souris traitées avec l’IL-21 montrent un retard dans la croissance des cellules B16 tumorales. Cette étude montre que l’IL-21 pourrait être utilisé comme stratégie pour le rétablissement du systeme immunitaire chez les personnes âgées.

Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1) is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs) previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for therapy of bovine and canine neosporosis.

Characterization of the Neospora caninum NcROP40 and NcROP2Fam-1 rhoptry proteins during the tachyzoite lytic cycle.

Virulence factors from the ROP2-family have been extensively studied in Toxoplasma gondii, but in the closely related Neospora caninum only NcROP2Fam-1 has been partially characterized to date. NcROP40 is a member of this family and was found to be more abundantly expressed in virulent isolates. Both NcROP2Fam-1 and NcROP40 were evaluated as vaccine candidates and exerted a synergistic effect in terms of protection against vertical transmission in mouse models, which suggests that they may be relevant for parasite pathogenicity. NcROP40 is localized in the rhoptry bulbs of tachyzoites and bradyzoites, but in contrast to NcROP2Fam-1, the protein does not associate with the parasitophorous vacuole membrane due to the lack of arginine-rich amphipathic helix in its sequence. Similarly to NcROP2Fam-1, NcROP40 mRNA levels are highly increased during tachyzoite egress and invasion. However, NcROP40 up-regulation does not appear to be linked to the mechanisms triggering egress. In contrast to NcROP2Fam-1, phosphorylation of NcROP40 was not observed during egress. Besides, NcROP40 secretion into the host cell was not successfully detected by immunofluorescence techniques. These findings indicate that NcROP40 and NcROP2Fam-1 carry out different functions, and highlight the need to elucidate the role of NcROP40 within the lytic cycle and to explain its relative abundance in tachyzoites.

Signalling in malaria parasites. The MALSIG consortium

Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense and respond to the intra- and the extra-cellular environments are therefore key elements for the proliferation and transmission of Plasmodium, and therefore are, from a public health perspective, strategic targets in the fight against this deadly disease. The MALSIG consortium, which was initiated in February 2009, was designed with the primary objective to integrate research ongoing in Europe and India on i) the properties of Plasmodium signalling molecules, and ii) developmental processes occurring at various points of the parasite life cycle. On one hand, functional studies of individual genes and their products in Plasmodium falciparum (and in the technically more manageable rodent model Plasmodium berghei) are providing information on parasite protein kinases and phosphatases, and of the molecules governing cyclic nucleotide metabolism and calcium signalling. On the other hand, cellular and molecular studies are elucidating key steps of parasite development such as merozoite invasion and egress in blood and liver parasite stages, control of DNA replication in asexual and sexual development, membrane dynamics and trafficking, production of gametocytes in the vertebrate host and further parasite development in the mosquito. This article, which synthetically reviews such signalling molecules and cellular processes, aims to provide a glimpse of the global frame in which the activities of the MALSIG consortium will develop over the next three years.