Targeting human telomeric G-quadruplex DNA with curcumin and its synthesized analogues under molecular crowding conditions

The formation of telomeric G-quadruplexes has been shown to inhibit telomerase activity. Indeed, a number of small molecules capable of p-stacking with G-tetrads have shown the ability to inhibit telomerase activity through the stabilization of G-quadruplexes. Curcumin displays a wide spectrum of medicinal properties ranging from anti-bacterial, anti-viral, anti-protozoal, anti-fungal and anti-inflammatory to anti-cancer activity. We have investigated the interactions of curcumin and its structural analogues with the human telomeric sequence AG(3)(T(2)AG(3))(3) under molecular crowding conditions. Experimental studies indicated the existence of a AG(3)(T(2)AG(3))(3)/curcumin complex with binding affinity of 0.72 x 10(6) M-1 under molecular crowding conditions. The results from UV-visible absorption spectroscopy, a fluorescent TO displacement assay, circular dichroism and molecular docking studies, imply that curcumin and their analogues interact with G-quadruplex DNA via groove binding. While other analogs of curcumin studied here bind to G-quadruplexes in a qualitatively similar manner their affinities are relatively lower in comparison to curcumin. The Knoevenagel condensate, a methoxy-benzylidene derivative of curcumin, also exhibited significant binding to G-quadruplex DNA, although with two times decreased affinity. Our study establishes the potential of curcumin as a promising natural product for G-quadruplex specific ligands.

The legacy of G. N. Ramachandran and the development of structural biology in India

G. N. Ramachandran is among the founding fathers of structural molecular biology. He made pioneering contributions in computational biology, modelling and what we now call bioinformatics. The triple helical coiled coil structure of collagen proposed by him forms the basis of much of collagen research at the molecular level. The Ramachandran map remains the simplest descriptor and tool for validation of protein structures. He has left his imprint on almost all aspects of biomolecular conformation. His contributions in the area of theoretical crystallography have been outstanding. His legacy has provided inspiration for the further development of structural biology in India. After a pause, computational biology and bioinformatics are in a resurgent phase. One of the two schools established by Ramachandran pioneered the development of macromolecular crystallography, which has now grown into an important component of modern biological research in India. Macromolecular NMR studies in the country are presently gathering momentum. Structural biology in India is now poised to again approach heights of the kind that Ramachandran conquered more than a generation ago.

Targeting human telomeric G-quadruplex DNA with curcumin and its synthesized analogues under molecular crowding conditions

The formation of telomeric G-quadruplexes has been shown to inhibit telomerase activity. Indeed, a number of small molecules capable of p-stacking with G-tetrads have shown the ability to inhibit telomerase activity through the stabilization of G-quadruplexes. Curcumin displays a wide spectrum of medicinal properties ranging from anti-bacterial, anti-viral, anti-protozoal, anti-fungal and anti-inflammatory to anti-cancer activity. We have investigated the interactions of curcumin and its structural analogues with the human telomeric sequence AG(3)(T(2)AG(3))(3) under molecular crowding conditions. Experimental studies indicated the existence of a AG(3)(T(2)AG(3))(3)/curcumin complex with binding affinity of 0.72 x 10(6) M-1 under molecular crowding conditions. The results from UV-visible absorption spectroscopy, a fluorescent TO displacement assay, circular dichroism and molecular docking studies, imply that curcumin and their analogues interact with G-quadruplex DNA via groove binding. While other analogs of curcumin studied here bind to G-quadruplexes in a qualitatively similar manner their affinities are relatively lower in comparison to curcumin. The Knoevenagel condensate, a methoxy-benzylidene derivative of curcumin, also exhibited significant binding to G-quadruplex DNA, although with two times decreased affinity. Our study establishes the potential of curcumin as a promising natural product for G-quadruplex specific ligands.

On the Geometrically Dependent Quasi-Saturation and g(m) Reduction in Advanced DeMOS Transistors

This paper reveals an early quasi-saturation (QS) effect attributed to the geometrical parameters in shallow trench isolation-type drain-extended MOS (STI-DeMOS) transistors in advanced CMOS technologies. The quasi-saturation effect leads to serious g(m) reduction in STI-DeMOS. This paper investigates the nonlinear resistive behavior of the drain-extended region and its impact on the particular behavior of the STI-DeMOS transistor. In difference to vertical DMOS or lateral DMOS structures, STI-DeMOS exhibits three distinct regions of the drain extension. A complete understanding of the physics in these regions and their impact on the QS behavior are developed in this paper. An optimization strategy is shown for an improved g(m) device in a state-of-the-art 28-nm CMOS technology node.

Direct numerical test of the B-G-K model equation by the DSMC method

In the present paper the rarefied gas how caused by the sudden change of the wall temperature and the Rayleigh problem are simulated by the DSMC method which has been validated by experiments both in global flour field and velocity distribution function level. The comparison of the simulated results with the accurate numerical solutions of the B-G-K model equation shows that near equilibrium the BG-K equation with corrected collision frequency can give accurate result but as farther away from equilibrium the B-G-K equation is not accurate. This is for the first time that the error caused by the B-G-K model equation has been revealed.

Comparaci��n de par��metros reproductivos bajo inseminaci��n artificial y monta natural en cerdas, (Cofradia, G.E.P.)

Este experimento se realiz�� en la Granja Experimental Porcina (G.E.P), Cofrad��a, Masaya, con 82 cerdas del cuarto parto, 30 servidas a trav��s de inseminaci��n artificial (I.A) y 52 cerdas por monta natural (M.N); iniciando en mayo de 1,995 hasta mayo de 1,996 con el objetivo de evaluar los par��metros reproductivos y econ��micos en ambos sistemas de monta. Los dos grupos de cerdas reproductoras estaban compuestos por las razas LANDRACE, YORKSHIRE y DUROC. Las variables evaluadas fueron: Tasa de concepci��n (T.C) y tasa de parici��n (T.P), n��meros de cr��as por partos (N.C.P), peso vivo promedio del lech��n en la camada al nacer (P.V.L.C), relaci��n beneficio-costo (B-C). Los resultados finales comprobados al 5% de significancia estad��sticas fueron: T.P en I.A con 56.66% menor que en M.N con 76.92%, en N.C.P para I.A con 7.06, menor que en M.N de 8.725, P.V.L.C en I.A de 1.85 kg, similar a 1.74 kg, en MN. Para la relaci��n B-C en I.A fue de 0.53 c��rdobas y para M.N de 0.56 c��rdobas.

Evaluaci��n de treinta y cuatro genotipos de frijol com��n (Phaseolus vulgaris L.) y dos genotipos de frijol tepari (Phaseolus acutifolius G.) en dos localidades del departamento de Carazo en el ciclo de postrera 2001

Durante la ��poca de postrera del 2001 se establecieron dos ensayos en las localidades La Compa����a y La Conquista pertenecientes al departamento de Carazo con el objetivo de evaluar el comportamiento de 34 genotipos de frijol com��n (Phaseolus vulgaris L.) y 2 genotipos de frijol tepari( Phaseolus acutifulius G.). en cuanto a caracteres de rendimiento y desarrollo. Estos materiales fueron proporcionados por el Centro Internacional de Agricultura Tropical (CIAT). El dise��o utilizado fue de bloques incompleto con 3 repeticiones. Los resultados de campo se procesaron mediante el programa de sistema an��lisis estad��stico (SAS), la prueba de rango m��ltiple de Tukey al 0.05 de error para las variables evaluadas y la correlaci��n de Pearson. Las variables evaluadas d��as a floraci��n, madurez fisiol��gica, peso de 100 granos, y rendimiento mostraron diferencias estad��sticas entre genotipos en cada localidad. La variable granos por vaina, solamente en una localidad result�� significativa, la variable n��mero de vainas por planta no fue significativa en ambas localidades, ning��n genotipo supero en cuanto al rendimiento a las variedades utilizadas como testigos. Los genotipos que superaron en precocidad a madurez fisiol��gica a los testigos en las dos localidades son INB 37, INB 39 y G 40068. Los genotipos con mayores incidencia al virus del mosaico dorado (BGMV) fueron SEA 15, SEA 17, SEA 19, SEA 21. SEA 22 y G 1977, los de mayor incidencia a mancha angular (Isariopsis griseo/a Sacc.) fueron G 40068, G 40159 y PINTO VILLA.

Immunosensor Interface Based on Physical and Chemical Immunogylobulin G Adsorption onto Mixed Self-Assembled Monolayers

An immunosensor interface based on mixed hydrophobic self-assembled monolayers (SAMs) of methyl and carboxylic acid terminated thiols with covalently attached human Immunoglobulin G (hIgG), is investigated. The densely packed and organised SAMs were characterised by contact angle measurements and cyclic voltammetry. The effect of the non-ionic surfactant, Tween 20, in preventing nonspecific adsorption is addressed by ellipsometry during physical and covalent hIgG immobilization on pure and mixed SAMs, respectively. It is clearly demonstrated that nonspecific adsorption due to hydrophobic interactions of hIgG on methyl ended groups is totally inhibited, whereas electrostatic/hydrogen bonding interactions with the exposed carboxylic groups prevail in the presence of surfactant. Results of ellipsometry and Atomic Force Microscopy, reveal that the surface concentration of covalently immobilized hIgG is determined by the ratio of COOH/CH3-terminated thiols in SAM forming solution. Moreover, the ellipsometric data demonstrates that the ratio of bound anti-hIgG/hIgG depends on the density of hIgG on the surface and that the highest ratio is close to three. We also report the selectivity and high sensitivity achieved by chronoamperometry in the detection of adsorbed hIgG and the reaction with its antibody.

Efecto de counter diez g (Terbufos) y fertilizante (N-P) sobre los nem��todos asociados a caf�� en vivero

El caf�� (coffea ar��biga L.) representa uno de los cultivos de mayor importancia en Nicaragua Este cultivo se ve afectado por nematodos fitoparasito de los g��neros Meloidogyne Spp. Pratylenchus spp0, y Rotylenchulus spp. Se prob�� el efecto de combinaciones del nematicida counter 10 G y fertilizante N-P sobre los nematodos fitoparasito con un ensayo en el Centro Experimental del Caf�� Mauricio L��pez Mungu��a���, Masatepe entre los meses de abril y Octubre de 1986. El dise��a utilizado fue en bifactorial en bloques completos al azar con cuatro repeticiones. Los tratamientos fueron al nematicida counter 10 G (terbufos) en dosis de 0; 017: 0.25 y 0, 32 gr de la planta; el fertilizante N-P de la f��rmula 18-46 o en dosis de 0.5 y 10 gr/planta, aplicados sobre y en combinaci��n lo que se Hizo un total de 12 tratamientos. la aplicaci��n del nematicida se hizo una sola vez y el fertilizante en dos ocasiones d. A los 55 y 100 DDA se midi�� el numero de nematodos en el suelo (Meloidogyne spp., Rotylenchulus spp, y pratylenchus spp) nematodos en las ra��ces (Meloidogyne spp), altura de planta, Numero de hojas y peso de ra��z. Los resultados de este ensayo demostraron qu�� el nematicida tuvo efecto sobre Rotylenchulus spp y Rotylenchulus spp. Pero no sobre Meloidogyne spp en el suelo y en la ra��z: No se encontr�� ning��n defecto del fertilizant4e sobre las poblaciones de nematodos. Las combinaciones de nematicida-fertilizante tuvieron un efecto de amplia variabilidad sobre las poblaciones de nematodos lo que dificulto la recomendaci��n de una determinada combinaci��n: La dosis de fertilizantes que resulto con los mejores promedios sobre las variables altura de la planta, N��mero de hojas y peso de ra��z fue la de 5gr, /planta Se encontr�� una correlaciona negativa significativa entre el g��nero Meloidogyne spp y la altura de la plata a los 55 DDA, no observ��ndose estos mismos resultados a los 100 DDA: tambi��n se encontr�� una correlaci��n positiva significativa entre el n��mero de Meloidogyne spp, del suelo y de la ra��z a los 55 y 100 DDA; entre pratylenchus y rotylenchulus a los 55 DDA y entere el n��mero de N��dulos causados por Meloidogyne a los 55 DDA y el peso de la Ra��z a los 100 DDA.

Dios entre las m��nadas : la centralidad del tema de Dios en algunas tesis metaf��sicas de G. W. Leibniz

Resumen: En el presente trabajo buscaremos introducir ciertas tesis distintivas del pensamiento de Leibniz en lo que respecta a su metaf��sica subrayando el papel de Dios en cada una de ellas. Fundamentalmente, las tesis a tratar son la teor��a de las m��nadas y dos teor��as que se siguen de ella: la de la armon��a preestablecida y la del mejor de los mundos posibles. Adem��s, buscaremos mostrar que las pruebas de la existencia de Dios (o al menos dos de ellas: el denominado ���argumento cosmol��gico��� y el denominado ���ontol��gico���), poseen subyacentemente una fundamentaci��n metaf��sica. En este sentido, no nos centraremos en las pruebas mismas sino en su fundamentaci��n.

Observaciones pr��cticas del uso del Disyston diez g. en el control de Sogata oryzicola M. en Nicaragua

El Disyston 10 G. es un insecticida sistemico selectivo y act��a por contacto, ��nicamente sobre plagas que viven en el suelo cuando el producto se ha disuelto. Aunque es muy estable y por lo tanto su residualidad muy prolongada, se puede aplicar en todo cultivo 70 d��as antes de la cosecha y se evita de esta manera repetir aplicaciones, lo cual significa beneficios econ��micos. EL buen control obtenido de S. oryzicola, usando este insecticida en el cultivo del arroz, ha proporcionado beneficios econ��micos dignos de tomarse en cuenta. As�� mismo, facilita el aprovechamiento del control biol��gico natural que para los casos aqu�� expuestos fue excelente. El control biol��gico inducido es de esperarse que tambi��n se realice. Para el caso especifico del arroz este insecticida debe usarse en los 80 d��as antes de la cosecha, dependiendo del grado de infestacion de S. oryzicola. Ademas de los insectos chupadores que controla, tambi��n resulta efectivo contra insectos que se movilizan en o debajo de la superficie del suelo, manifestando al mismo tiempo un efecto secundario sobre nematodos. Su aplicaci��n tiene la ventaja sobre las formas convencionales, en que por ser granulado y con suficiente peso no es arrastrado por el viento de regular intensidad, los cuales resultar��an desastrosos para formulaciones emulsionables y en polvo. Durante se realizaron los recuentos, la S. oryzicola mantuvo niveles reducidos, ayudando en esta forma a mantener los predadores y par��sitos, los cuales emigrar��an, si la S. oryzicola se eliminara totalmente. Este bajo nivel de poblaci��n que permaneci�� en la plantaci��n no fue suficiente para provocar la aparici��n de s��ntomas de Hoja Blanca en el cultivo y en el grado necesario para disminuir la producci��n de grano.

Numerical simulation of g-jitter effects on half floating zone convection under microgravity environment

The g-jitter effects on the thermocapillary convection in liquid bridge of floating half zone were studied by numerical simulation for unsteady and axi-symmetric model in the cylindrical coordinate system. The g-jitter field was given by a steady microgravity field in addition to an oscillatory low-gravity field, and the effects on the flow field, temperature distribution and free surface deformation were analyzed numerically.

G-jitter effects on half floating-zone convection in intermediate-frequency range

The g-jitter influence on thermocapillary convection and critical Marangoni number in a liquid bridge of half-floating rone was discussed in the low frequency range of 0.4 to 1.5 Hz in a previous paper. This paper extended the experiments to the intermediate frequency range of 2 to 18 Hz, which htrs often been recorded as vibration environment of spacecrafts. The experiment was completed on the deck of a vibration machine, which gave a periodical applied acceleration to simulate the effects of g-jitter. The experimental results in the intermediate frequency range are different from that in the low frequency range. The velocity field and the shape of the free surface have periodical fluctuations in response to g-jitter. The amplitude of the periodical varying part of the temperature response decreases obviously with increasing frequency of g-jitter and vanishes almost when the frequency of g-jitter is high enough. The critical Marangoni number is defined to describe the transition from a periodical convection in response to g-jitter to an oscillatory convection due to internal instability, and will increase with increasing g-jitter frequency. According to the spectral analysis, it can be found that the oscillatory part of temperature is a superposition of two harmonic waves if the Marangoni number is larger than a critical value.