Metabolism and actions of 2 -chloro-2$\sp\prime$-fluoro-arabinosyladenine

2-Chloro-9-(2-deoxy-2-fluoro-$\beta $-D-arabinofuranosyl)adenine(Cl-F-ara-A) is a new deoxyadenosine analogue which is resistant to phosphorolytic cleavage and deamination, and exhibits therapeutic activity for both leukemia and solid tumors in experimental systems. To characterize its mechanism of cytotoxicity, the present study investigated the cellular pharmacology and the biochemical and molecular mechanisms of action of Cl-F-ara-A, from entrance of the drug into the cell, chemical changes to active metabolites, targeting on different cellular enzymes, to final programmed cell death response to the drug treatment.^ Cl-F-ara-A exhibited potent inhibitory action on DNA synthesis in a concentration-dependent and irreversible manner. The mono-, di-, and triphosphates of Cl-F-ara-A accumulated in cells, and their elimination was non-linear with a prolonged terminal phase, which resulted in prolonged dNTP depression. Ribonucleotide reductase activity was inversely correlated with the cellular Cl-F-ara-ATP level, and the inhibition of the reductase was saturated at higher cellular Cl-F-ara-ATP concentrations. The sustained inhibition of ribonucleotide reductase and the consequent depletion of deoxynucleotide triphosphate pools result in a cellular Cl-F-ara-ATP to dATP ratio which favors analogue incorporation into DNA.^ Incubation of CCRF-CEM cells with Cl-F-ara-A resulted in the incorporation of Cl-F-ara-AMP into DNA. A much lesser amount was associated with RNA, suggesting that Cl-F-ara-A is a more DNA-directed compound. The site of Cl-F-ara-AMP in DNA was related to the ratio of the cellular concentrations of the analogue triphosphate and the natural substrate dATP. Clonogenicity assays showed a strong inverse correlation between cell survival and Cl-F-ara-AMP incorporation into DNA, suggesting that the incorporation of Cl-F-ara-A monophosphate into DNA is critical for the cytotoxicity of Cl-F-ara-A.^ Cl-F-ara-ATP competed with dATP for incorporation into the A-site of the extending DNA strand catalyzed by both DNA polymerase $\alpha$ and $\varepsilon$. The incorporation of Cl-F-ara-AMP into DNA resulted in termination of DNA strand elongation, with the most pronounced effect being observed at Cl-F-ara-ATP:dATP ratio $>$1. The presence of Cl-F-ara-AMP at the 3$\sp\prime$-terminus of DNA also resulted in an increased incidence of nucleotide misincorporation in the following nucleotide position. The DNA termination and the nucleotide misincorporation induced by the incorporation of Cl-F-ara-AMP into DNA may contribute to the cytotoxicity of Cl-F-ara-A. ^

The antiapoptotic effect of overexpression c -erBb2 in breast cancer

Overexpression of the receptor tyrosine kinase p185ErbB2 confers taxol resistance in breast cancers and activation of p34Cdc2 is required for taxol-induced apoptosis and cytotoxicity. Here, we investigated the underlying mechanisms and found that overexpression of p185 ErbB2 inhibits taxol-induced apoptosis through two branches to inhibit activation of p34Cdc2. ^ Overexpression of p185ErbB2 in MDA-MB-435 cells by transfection transcriptionally upregulated p21Cip1, which associates with p34Cdc2, inhibits taxol-mediated p34Cdc2 activation, delays cell entrance to G2/M phase, and thereby inhibits taxol-induced apoptosis. In p21Cip1 antisense-transfected MDA-MB-435 cells or in p21−/− MEF cells, p185ErbB2 was unable to inhibit taxol-induced apoptosis. Therefore, p21Cip1 participates in the regulation of a G2/M checkpoint that contributes to resistance to taxol-induced apoptosis in p185ErbB2-overexpressing breast cancer cells. ^ Direct phosphorylation on Tyrosine-15 of p34Cdc2 by p185 ErbB2 receptor tyrosine kinase inhibits p34Cdc2 activation. The wild-type p185ErbB2 but not the kinase-defective mutant, when overexpressed in breast cancer cells, can phosphorylate p34Cdc2 on tyrosine (Tyr)15, an inhibitory phosphorylation site of p34 Cdc2. The kinase domain of the ErbB2 receptor was sufficient for binding to p34Cdc2 and directly phosphorylating the recombinant Cdc2. Phosphospecific Cdc2-Tyr15 immunoblot analyses, immunocomplex kinase assays, and phospho-amino acid analyses revealed that p185ErbB2 specifically phosphorylates Cdc2 on Tyr15. Phosphorylation of Cdc2-Tyr15 by ErbB2 is modulated during cell cycle and corresponded with delayed cell entry into G2/M phase. The kinase-defective p185ErbB2, which incapable of phosphorylating Cdc2-Tyr15, failed to inhibit taxol-induced activation and apoptosis, whereas the wild-type and the constitutive-active p185ErbB2 did. Increased Cdc2-Tyr15 phosphorylation was found in Erb132-overexpressing tumors from breast cancer patients. Thus, direct phosphorylation of Cdc2-Tyr15 by p185 ErbB2 RTK in breast cancer cells inhibits taxol-induced p34 Cdc2 activation and apoptosis, thereby conferring taxol resistance. ^

Strain-gauge, brushless torque meter

A torque meter comprising hollow-keyed, input and output female shafts adapted to receive the male shafts of the power source and machine respectively. Each shaft has a circular flange whose face is perpendicular to the center line of the shafts. Each flange has a plurality of equally spaced cylindrical recesses machined into the inside face thereto adapted to receive conical inserts therein. Balls are contained by the conical inserts and transmit the rotational movement from the input to the output shaft. A stationary housing extends around the input and output shaft and has a transducer shell secured thereto. When force is applied to the input shaft to cause movement, the balls encounter torsional resistance which causes the balls to roll up the ramps of the conical seat inserts to separate the two torque flanges. The force transmitted through the balls causes rotation to the output shaft and produces tension to the stationary transducer shell. The stationary transducer shell is instrumented with semi-conductor strain gauges.

Geological investigations on sediment core MD07-3128

Glacial millennial-scale paleoceanographic changes in the Southeast Pacific and the adjacent Southern Ocean are poorly known due to the scarcity of well-dated and high resolution sediment records. Here we present new surface water records from sediment core MD07-3128 recovered at 53°S off the Pacific entrance of the Strait of Magellan. The alkenone-derived sea surface temperature (SST) record reveals a very strong warming of ca. 8°C over the last Termination and substantial millennial-scale variability in the glacial section largely consistent with our planktonic foraminifera oxygen isotope (d18O) record of Neogloboquadrina pachyderma (sin.). The timing and structure of the Termination and some of the millennial-scale SST fluctuations are very similar to those observed in the well-dated SST record from ODP Site 1233 (41°S) and the temperature record from Drowning Maud Land Antarctic ice core supporting the hemispheric-wide Antarctic timing of SST changes. However, differences in our new SST record are also found including a long-term warming trend over Marine Isotope Stage (MIS) 3 followed by a cooling toward the Last Glacial Maximum (LGM). We suggest that these differences reflect regional cooling related to the proximal location of the southern Patagonian Ice Sheet and related meltwater supply at least during the LGM consistent with the fact that no longer SST cooling trend is observed in ODP Site 1233 or any SST Chilean record. This proximal ice sheet location is documented by generally higher contents of ice rafted debris (IRD) and tetra-unsaturated alkenones, and a slight trend toward lighter planktonic d18O during late MIS 3 and MIS 2.

Physical oceanography during UPAT cruise to the Amvrakikos Gulf, August 2009

Oceanographic research in the Amvrakikos Gulf in Western Greece, a semi-enclosed embayment isolated from the Ionian Sea by a narrow, shallow sill, has shown that it is characterised by a fjord-like oceanographic regime. The Gulf is characterised by a well-stratified two layer structure in the water column made up of a surface layer and a bottom layer that are separated by a strong pycnocline. At the entrance over the sill, there is a brackish water outflow in the surface water and a saline water inflow in the near-bed region. This morphology and water circulation pattern makes the Amvrakikos Gulf the only Mediterranean Sea fjord. The investigations have also shown that the surface layer is well oxygenated, whereas in the pycnocline, the dissolved oxygen (DO) declines sharply and finally attains a value of zero, thus dividing the water column into oxic, dysoxic and anoxic environments. At the dysoxic/anoxic interface, at a depth of approximately 35 m, a sharp redox cline develops with Eh values between 0 and 120 mV occurring above and values between 0 and -250 mV occurring below, where oxic and anoxic biochemical processes prevail, respectively. On the seafloor underneath the anoxic waters, a black silt layer and a white mat cover resembling Beggiatoa-like cells are formed. The dysoxic/anoxic conditions appeared during the last 20 to 30 years and have been caused by the excessive use of fertilisers, the increase in animal stocks, intensive fish farming and domestic effluents. The inflicted dysoxia/anoxia has resulted in habitat loss on the seafloor over an area that makes up just over 50% of the total Gulf area and approximately 28% of the total water volume. Furthermore, anoxia is also considered to have been responsible for the sudden fish mortality which occurred in aquaculture rafts in the Gulf in February 2008. Therefore, anoxic conditions can be considered to be a potential hazard to the ecosystem and to the present thriving fishing and mariculture industry in the Gulf.

Método de evaluación a campo de la resistencia al moho azul en clones de ajo tipo colorado

Con el objeto de ajustar un método de evaluación a campo para facilitar la selección de clones de ajo (Allium sativum L.) con resistencia a Penicillium allii, se realizó un ensayo replicado en el cual se midió la respuesta de tres clones experimentales a la infección, en dos épocas de plantación. Los tratamientos incluyeron combinaciones de presencia o ausencia de: a) desinfección de la "semilla", b) heridas artificiales en los bulbillos, c) inoculación artificial. Los bulbillos con la hoja envolvente se desinfectaron con una solución diluida de hipoclorito de sodio. La inoculación se realizó mediante la inmersión en una solución de 106 esporas•ml-1. Las heridas se realizaron con una lanceta (blood lancet). Los bulbillos se incubaron en cámara húmeda durante 24 horas a 20 °C, antes de plantación. Las variables respuestas computadas fueron las siguientes: número de plantas muertas, y vivas con síntomas y sin síntomas, a los 152 días de plantación en la primera época y 118 días en la segunda; número de bulbos por calibres y rendimiento a cosecha. La información obtenida se analizó a través de correspondencia simple, diferencia de proporciones y análisis paramétricos. Se detectaron mayores diferencias entre los tratamientos en la tasa de sobrevivencia y en la proporción de calibres comerciales en la época tardía. No se observaron diferencias (p < 0,05) del rendimiento en la plantación temprana. La herida fue determinante en el ingreso del patógeno. Los tratamientos quedaron limitados a un testigo: desinfectado, no inoculado y sin herida, y a un tratamiento: desinfectado, con inoculación y herida. Con respecto a la época, resultó conveniente la evaluación en plantaciones tardías porque se expresan mejor las diferencias entre los tratamientos.

Trips (Frankliniella brevicaulis Hood) de las erupciones del fruto de banano (Musa acuminata Colla) en la provincia de Formosa, Argentina

El banano en la provincia de Formosa (Argentina) es uno de los principales cultivos de renta y generador de mano de obra para el productor por lo que representa un importante lugar en lo social y económico. La sanidad de los cultivos es fundamental para lograr una mayor rentabilidad. Se han observado en los frutos daños atribuibles a trips. Los objetivos de este trabajo fueron identificar la/s especie/s de trips causal de las erupciones del fruto de banano en la provincia de Formosa, realizar una descripción detallada de su morfología y caracterizar y evaluar los daños producidos. La zona de trabajo correspondió al Área-Laguna Naineck en el Departamento Pilcomayo de la provincia de Formosa considerando un total de 1.103,74 ha pertenecientes a 233 productores. Para la determinación del estado sanitario de las plantaciones con respecto a la presencia del insecto se realizó un diseño de muestreo estadístico. Se recolectaron muestras del insecto y se identificaron con ayuda de claves. La única especie de trips encontrada fue Frankliniella brevicaulis. Los daños producidos por esta especie serían debidos a las heridas causadas por la oviposición, siendo éstas posibles fuentes de entrada para el hongo Colletotrichum musae. Se observaron daños en el 100% de los cachos de banana en todas las plantaciones evaluadas.

Análisis de los factores explicativos de la rentabilidad de las empresas vinícolas de Castilla-La Mancha

El sector del vino experimenta, en las últimas décadas, un vertiginoso proceso de cambio y nuevas dinámicas, que están afectando el desempeño y estrategias de las empresas del sector: internacionalización creciente, caída de los mercados internos de los países tradicionalmente productores, entrada de capital exógeno, etc. La pericia que muestre la organización para adecuarse a la nueva situación se reflejará en la rentabilidad, indicador básico para juzgar la eficiencia en la gestión empresarial. En este estudio, a partir de una muestra representativa de empresas de Castilla-La Mancha, región española con la mayor dimensión vinícola mundial, se ha planteado un modelo econométrico novedoso integrado por variables de desempeño, definidas con la técnica de componentes principales. De los resultados obtenidos se infiere que la rentabilidad de las empresas proviene de: a) su estructura societaria (mayor si son empresas capitalistas que sociedades cooperativas), b) de su tamaño (mejor desempeño a mayor tamaño, aprovechando economías de escala), y c) estructura financiera (mayor rentabilidad si en la composición de la misma priman los recursos propios y liquidez). Por el contrario, la falta de financiación permanente para hacer frente al activo fijo y una dinámica comercial más orientada hacia las ventas de vino a granel a bajo precio, reducen significativamente los ratios de rentabilidad.

Benthic and planktonic foraminifera of sediment core GIK17957-2

A detailed age model for core 17957-2 of the southern South China Sea was developed based on delta18O, coarse fraction, magnetostratigraphy, and biostratigraphy for the last 1500 kyr. The delta18O record has clear ~100-kyr cycles after the Mid-Pleistocene Revolution (MPR) at the entrance of marine isotopic stage (MIS) 22. Planktonic foraminifera responded to the MPR immediately, showing the increased sea surface temperature (SST) and dissolution after the MPR. Benthic foraminifera did not respond to it until the Brunhes/Matuyama boundary. Since the MPR, the depth of thermocline gradually became shallower until MISs 6-5. This major change within MISs 6-5 was also reflected in the decreased SSTs and increased productivity and Deep Water Mass. Thus two major Pleistocene paleoceanographic changes were found: One was around the MPR; the other occurred within MISs 6-5, which speculatively might be ascribed to the reorganization of surface and deep circulation, possibly induced by tectonic forces.

Aerosols over the Arabian Sea

This paper provides an overview of dust transport pathways and concentrations over the Arabian Sea during 1995. Results indicate that the transport and input of dust to the region is complex, being affected by both temporally and spatially important processes. Highest values of dust were found off the Omani coast and in the entrance to the Gulf of Oman. Dust levels were generally lower in summer than the other seasons, although still relatively high compared to other oceanic regions. The Findlater jet, rather than acting as a source of dust from Africa, appears to block the direct transport of dust to the open Arabian Sea from desert dust source regions in the Middle East and Iran/Pakistan. Dust transport aloft, above the jet, rather than at the surface, may be more important during summer. In an opposite pattern to dust, sea salt levels were exceedingly high during the summer monsoon, presumably due to the sustained strong surface winds. The high sea salt aerosols during the summer months may be impacting on the strong aerosol reflectance and absorbance signals over the Arabian Sea that are detected by satellite each year.

Geochemical composition and granulometry of ODP Hole 167-1017E sediments

Intensification of North Pacific Intermediate Water during the Younger Dryas and stadials of the last glacial episode has been advocated by Kennett and his colleagues based on studies of ventilation history in Santa Barbara Basin. Because Santa Barbara Basin is a semi-isolated marginal basin, this hypothesis requires testing in sequences on the upper continental margin facing the open-ocean of the Pacific. Ocean Drilling Program Site 1017 is located on the upper slope of southern California off Point Conception close to the entrance of Santa Barbara Basin, an ideal location to test the hypothesis of late Quaternary switching in intermediate waters. We examined chemical and mineral composition, sedimentary structures, and grain size of hemipelagic sediments representing the last 80 k.y. at this site to detect changes in behavior of intermediate waters. We describe distinct compositional and textual variations that appear to reflect changes in grain size in response to flow velocity fluctuations of bottom waters. Qualitative estimates of changes in degree of pyritization indicate better ventilation of bottom water during intervals of stronger bottom-water flow. Comparison between variations in the sediment parameters and the planktonic d18O record indicates intensified bottom-current activity during the Younger Dryas and stadials of marine isotope Stage 3. This result strongly supports the hypothesis of Kennett and his colleagues. Our investigation also suggests strong grain-size control on organic carbon content (and to less extent carbonate carbon content). This, in turn, suggests the possibility that organic carbon content of sediments, which is commonly used as an indicator of surface productivity, can be influenced by bottom currents.

Nannofossil datums and abundance in sediments from ODP Leg 164 sites

Twenty routinely used nannofossil datums in the late Neogene and Quaternary were identified at three Blake Ridge sites drilled during Leg 164. The quantitative investigation of the nannofossil assemblages in 236 samples selected from Hole 994C provide new biostratigraphic and paleoceanographic information. Although mostly overlooked previously, Umbilicosphaera aequiscutum is an abundant component of the late Neogene flora, and its last occurrence at ~2.3 Ma is a useful new biostratigraphic event. Small Gephyrocapsa evolved within the upper part of Subzone CN11a (~4.3 Ma), and after an initial acme, it temporarily disappeared for 400 k.y., between 2.9 and 2.5 Ma. Medium-sized Gephyrocapsa evolved in the latest Pliocene ~2.2 Ma), and after two short temporary disappearances, common specimens occurred continuously just above the Pliocene/Pleistocene boundary. The base of Subzone CN13b should be recognized as the beginning of the continuous occurrence of medium-sized (>4 µm) Gephyrocapsa. Stratigraphic variation in abundance of the very small placoliths and Florisphaera profunda alternated, indicating potential of the former as a proxy for the paleoproductivity. At this site, it is likely that upwelling took place during three time periods in the late Neogene (6.0-4.6 Ma, 2.3-2.1 Ma, and 2.0-1.8 Ma) and also in the early Pleistocene (1.4-0.9 Ma). Weak upwelling is also likely to have occurred intermittently through the late Pliocene. Due to the sharp and abrupt turnover of the nannofossils, which resulted from an evolution of very competitive species, the paleoproductivity of the late Pleistocene is not clear. The site was mostly in an oligotrophic central gyre setting during the 4.6- to 2.3-Ma interval, intermittently between 2.1 and 1.4 Ma, and continuously for the last several tens of thousand years.

Vocational guidance in people with special educational needs as the result of visual impairment during the transition stage from high school to advanced education

This work proposes to seek for the factors related to the choices that people with special educational needs make as the result of the visual impairment, during the transition stage from high school to advanced education. Therefore, we have taken into consideration that Vocational Guidance and the transition towards adulthood get specific characteristics in case of visually impaired young people, particularly in what's related to continue with advanced education. The focus of this work is to be able to clarify the existence of factors that make this transition stage easier or harder, through the observation of visually impaired and blind people who complete high school. This matter has aroused interest and concern about the strategies to follow to ensure the successful entrance and remaining in the selected advanced education. However, if we don?t know the factors involved in the described fact, it's difficult to design an appropriate intervention strategy. Then, in order to take acknowledge about the specific issues of visually impaired young people who complete high school, we chose a special school for this disability and some students who will join this project