Prognostic significance of cathepsin-D in patients with breast cancer

The expression of the protease cathepsin-D has been evaluated using an immunohistochemical technique with a polyclonal antibody in paraffin-embedded tissue from 359 patients treated between the years 1975-1981 for Stage I and II breast cancer. One hundred and twenty seven patients (35%) have strongly positive, granular staining, 138 (38%) are intermediately stained in the cytoplasm, and in 94 (26%) no staining is observed. There is a strong positive association between expression of cathepsin-D and the presence of tumour in axillary lymph nodes (P < 0.006). Expression of the protease is associated with significantly poorer survival of patients in univariate analysis (P = 0.025); however, this is not independent of other tumour variables.     

RNA tertiary structure mediation by adenosine platforms

The crystal structure of a group I intron domain reveals an unexpected motif that mediates both intra- and intermolecular interactions. At three separate locations in the 160-nucleotide domain, adjacent adenosines in the sequence lie side-by-side and form a pseudo-base pair within a helix. This adenosine platform opens the minor groove for base stacking or base pairing with nucleotides from a noncontiguous RNA strand. The platform motif has a distinctive chemical modification signature that may enable its detection in other structured RNAs. The ability of this motif to facilitate higher order folding provides one explanation for the abundance of adenosine residues in internal loops of many RNAs.     

Multiple solution conformations of the integrin-binding cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-). Analysis of the (phi, psi) space available to cyclic pentapeptides

The aqueous solution structure of the cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-) has been determined by two-dimensional 1H-NMR spectroscopy, combined with a conformational search and distance-geometry calculations. As many as five conformers in slow exchange were observed, and the rate of interconversion between components was measured from the build-up rates of exchange peaks. NMR data allowed the structures of the two predominant conformers to be determined. The major component (66%) contained a cis-proline as part of a type-VIa2 beta-turn encompassing residues Asp-Val-cis-Pro-Ser. The second component (16%) contained only trans-amide bonds, and a type-VIII beta-turn formed by residues Val-Pro-Ser-D-Leu. These structures are discussed in relation to the (phi, psi), space available to the cyclic pentapeptide, determined by a conformational search, and in relation to previously published cyclic-pentapeptide structures. The molecule exhibits activity in a scintillation-proximity assay for the inhibition of the interaction between the integrin very-late antigen-4 (VLA-4; alpha 4 beta 1) and vascular-cell-adhesion molecule-1 (VCAM-1). The structure/activity relationship of the LDV sequence is discussed and related to the recently published X-ray structure of VCAM-1. The relevance of the work to the design of anti-inflammatory drugs is discussed.     

p-aminohippurate uptake by syncytial microvillous membrane vesicles of human term placenta

The mechanism of uptake of p-aminohippurate (PAH) by syncytial microvillous membrane vesicles of human term placenta was investigated. Initial PAH uptake and efflux were increased in the presence of a pH-gradient and a Cl(-)-gradient, respectively. Forced negative and positive membrane potentials did not influence the uptake, which indicated that the transport is not electrogenic. The pH-dependent increase is probably the result of a higher rate of diffusion due to a lower degree of dissociation of PAH. Because several organic anions failed to transstimulate PAH uptake and FCCP did not decrease the uptake in the presence of an inwardly directed H(+)-gradient, ruling out a PAH/OH- antiport, an anion exchange system does not appear to be present in these membranes. Since electrogenicity and anion exchange seem not to be involved in the Cl(-)-dependent increase, an allosteric effect of Cl- on the transporter might be possible. Various organic anions were able to inhibit pH-stimulated PAH uptake significantly. Kinetic analysis of the probenecid sensitive part of uptake provided further evidence for mediated transport of PAH (Km = 7.4 +/- 2.6 mM and Vmax = 2.0 +/- 0.4 nmol/mg/15 s). Non-inhibitable diffusion accounted for the main part of total transport. Concentration dependent inhibition of PAH transport by probenecid showed a Ki of 2.5 +/- 0.9 mM. It is concluded that human placental syncytial microvillous membrane vesicles possess a low affinity transport mechanism for PAH with low specificity. The importance of this system, for placental excretion of anionic drugs, will depend on the intrasyncytial concentration of these drugs, caused by the transport across the basal membrane.     

Application of condition-based HRA method for a manual actuation of the safety features in a nuclear power Plant

A practical approach to develop a more realistic fault-tree model with a consideration of various conditions endured by a human operator is proposed. In safety-critical systems, the generation failure of an actuation signal is caused by the concurrent failures of the automated systems and an operator action. These two sources of safety signals are complicatedly correlated. The failures of sensors or automated systems will cause a lack of necessary information for a human operator and result in error-forcing contexts such as the loss of corresponding alarms and indications. It is well known that the error-forcing contexts largely affect the operator's performance. An automated system which consists of multiple processing channels and complex components is also affected by the availability of the sensors. This paper proposes a condition-based human reliability assessment (CBHRA) method in order to address these complicated conditions in a practical way. We apply the CBHRA method to the manual actuation of the safety features such as a reactor trip and auxiliary feedwater actuation in Korean Standard Nuclear Power Plants. Even the human error probability of each given condition is simply assumed, the application results prove that the CBHRA effectively accommodates the complicated error-forcing contexts into the fault trees.     

A study on UV-curable coatings for HD-DVD: Primer and top coats

This study relates to the development of coatings for optical discs in high-density digital versatile disc systems (HD-DVD or blue lay disk) that use a high numerical aperture of 0.85 at 405 nm wavelength and have a protective top layer over a primer layer for protection against damage and dust. Ultraviolet-curable raw materials of two acrylic monofunctional monomers ( isobornylacrylate, IBA and tetrahydrofurfurylacrylate, THFA) and two kinds of urethaneacrylate oligomers (OUMD and OUME) have been easily mixed with photoinitiators. Curing rate of these materials was characterized by FT-IR. In case of top coats, VTES (vinyltriethoxysilane) and acrylic acid were added to enhance the abrasion resistance. These two kinds of UV-curable resinous materials having no solvent were synthesized and investigated as means for making a blue ray disk having good optical and mechanical properties. In addition, dynamic characteristics including reflectivity, fluctuation of RF signal and noise level were also investigated.