Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas
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1694 research outputs found
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Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A
No full textBackground: The CDKN2/INK4A tumour suppressor gene is deleted or mutated in a large number of human cancers. Overexpression of its product, p16, has been shown to block the transition through the G1/S phase of the cell cycle in a pRb-dependent fashion by inhibiting the cyclin D-dependent kinases cdk4 and cdk6. Reconstitution of p16 function in transformed cells is therefore an attractive target for anti-cancer drug design.
Results: We have identified a 20-residue synthetic peptide--corresponding to amino acids 84-103 of p16--that interacts with cdk4 and cdk6, and inhibits the in vitro phosphorylation of pRb mediated by cdk4-cyclin D1. The amino-acid residues of p16 important for its interaction with cdk4 and cdk6 and for the inhibition of pRb phosphorylation were defined by an alanine substitution series of peptides. In normal proliferating human HaCaT cells and in cells released from serum starvation, entry into S phase was blocked by the p16-derived peptide when it was coupled to a small peptide carrier molecule and applied directly to the tissue culture medium. This cell-cycle block was associated with an inhibition of pRb phosphorylation in vivo.
Conclusions: These results demonstrate that a p16-derived peptide can mediate three of the known functions of p16: firstly, it interacts with cdk4 and cdk6; secondly, it inhibits pRb phosphorylation in vitro and in vivo; and thirdly, it blocks entry into S phase. The fact that one small synthetic peptide can enter the cells directly from the tissue culture medium to inhibit pRb phosphorylation and block cell-cycle progression makes this an attractive approach for future peptidometic drug design. Our results suggest a novel and exciting means by which the function of the p16 suppressor gene can be restored in human tumours
Automated control system for HgI2 crystals growth
No full textWe describe the control system developed for the automated growth of HgI2 crystals, mainly used for X and gamma radiation detectors. The system includes instrumentation for the precise measurement of the growth furnace temperatures and for their control, both needed to fulfill the strict requirements of the vapour phase crystal growth. A video camera and a VME grabber module allow the detection of the crystal nucleation and pattern recognition.
This image analysis is used as input for the control actions. A VME based computer (MVM147SA-1 from Motorola) running a real time OS9 operating system performs: data collection, instrumentation programming, image acquisition, data analysis and control of the whole system making use of a highly structured software. The image analysis is done by means of a perceptron neural net classifier using a parameter invariant representation of the objects detected in the segmented images
Design of a modified uniform redundant-array mask for portable gamma cameras
No full textUniform redundant-array masks have been reported as good lenses to form the image of gamma sources, with the correlation between the mask-aperture matrix and the shadows projected on a static position-sensitive detector. We present a modified uniform redundant-array configuration suitable for portable and small-size y cameras; its ability to reconstruct the image of several sources is analyzed. We have carried out a Montecarlo simulation of the gamma interactions in the mask, defining the expected response of the correlation process and comparing it with that achieved with the usual uniform redundant-array configuration
