A. Wong

Role of cathepsin K in structural changes in brachiocephalic artery during progression of atherosclerosis in apoE-deficient mice

Cathepsin K, a potent extracellular matrix degrading cysteine protease, has been linked to the pathogenesis of osteoporosis, arthritis, cardiovascular and respiratory diseases. Here, we report the effects of cathepsin K deficiency (ctsK-/-) on atherosclerotic plaque formation in brachiocephalic arteries in an aggressive atherosclerosis model using apoE-deficient mice on cholate-containing high fat diet (HFD). On this diet, apoE-/- mice displayed severe lesions with buried fibrous caps after 8 weeks, whereas the apoE-/-ctsK-/- mice revealed a significantly decreased number of buried fibrous caps accompanied by increased collagen content in plaque areas and fibrous cap thickness. After 16 weeks of HFD, ctsK-/- mice had smaller plaque areas and maintained the structure of the tunica media in terms of their smooth muscle cell content and elastic lamina integrity. Overall macrophage content in the tunica media was lower in ctsK-/- mice but higher in the plaque area after 8 weeks of HFD. Decreased apoptosis rates in atherosclerotic plaques in brachiocephalic arteries of cathepsin K-deficient indicated a lower level of inflammation. In conclusion, cathepsin K deficiency appears to increase lesion stability in brachiocephalic arteries by maintaining the integrity of the tunica media and by decreasing plaque vulnerability to rupture.

A planar method for patterning of high‐temperature superconducting films and multilayers

We present a novel technique for patterning high‐temperature superconducting (HTS) film and multilayer device structures. In the process an impurity ion (e.g., Si) is implanted into HTS films through a photoresist mask. The impurity ions convert the irradiated portion of the film into an insulating form by chemical reaction between the ions and the oxygen in the film, without altering the overall crystalline structure of the film. Removal of the photoresist results in a flat surface, which allows the epitaxial growth and implantation patterning of subsequent films so that a complete multilayer device structure can be fabricated. We show in detail the patterning process, as well as the properties of patterned and regrown films. Some simple device structures, such as a vertical contact and a crossover, are demonstrated.

Elastin degradation by cathepsin V requires two exosites

Background: Elastin degradation is a key event in various pathologies of the skin, lung, and the vascular system. Results: Elastin degradation by cathepsin V requires two exosites. Conclusion: Cathepsin exosites support the recognition of and binding to insoluble elastin. Significance: Exosites may represent novel target sites for the selective inhibition of the elastase activity of cathepsins. Cathepsin V is a highly effective elastase and has been implicated in physiological and pathological extracellular matrix degradation. However, its mechanism of action remains elusive. Whereas human cathepsin V exhibits a potent elastolytic activity, the structurally homologous cathepsin L, which shares a 78% amino acid sequence, has only a minimal proteolytic activity toward insoluble elastin. This suggests that there are distinct structural domains that play an important role in elastinolysis. In this study, a total of 11 chimeras of cathepsins V and L were generated to identify elastin-binding domains in cathepsin V. Evaluation of these chimeras revealed two exosites contributing to the elastolytic activity of cathepsin V that are distant from the active cleft of the protease and are located in surface loop regions. Replacement of exosite 1 or 2 with analogous residues from cathepsin L led to a 75 and 43% loss in the elastolytic activity, respectively. Replacement of both exosites yielded a non-elastase variant similar to that of cathepsin L. Identification of these exosites may contribute to the design of inhibitors that will only affect the elastolytic activity of cysteine cathepsins without interfering with other physiological protease functions.

REPRODUCIBLE GROWTH OF HIGHLY CRYSTALLINE YBA2CU3O7 THIN FILMS ON SRTIO3 BY SCANNING PULSED LASER DEPOSITION

YBa2Cu3O7 (YBCO) thin films were grown on SrTiO3 substrates using a pulsed laser deposition system. The laser beam was scanned over the target in such a way to obtain a reproducible method of composition control at the substrate. In total, 17 films were grown under optimal conditions; they exhibited mean transition temperatures of 89.7±0.4 K and mean (005) rocking curve widths of 0.07°±0.02°. The narrowest (005) rocking curve width was measured to be 0.037°. Both the rocking curve line shapes and the dependence of transition temperature on rocking curve width suggest the films have single-crystal-like structure.

Inhibition patterning of oxide superconducting films with Si ion implantation

A new method of inhibition patterning of oxide superconducting (YBCO) films is presented. With implanted Si ions, the YBCO film loses its electrical conductivity and diamagnetism, while its crystalline structure is preserved. The method allows the growth of a second epitaxial YBCO layer on top of the inhibited area, thus providing an effective method of patterning oxide superconductor multilayer structures. Micrometre-sized superconducting lines have been patterned by Si ion implantation with a photoresist mask. Both patterned structures and second-layer films have superconducting properties similar to those of pure YBCO films.

Ion implantation in high temperature superconducting films

Reactive ion implantation (RII) has been used to inhibit superconductivity in oxide superconductor materials. By introducing ions which are chemically reactive with oxygen into a high temperature superconductor (HTS) oxide film, the conductivity of the material may be inhibited by the interaction of the implanted ions with the oxygen in the oxide. Both Si and B ions, with doses ranging from 1/spl times/10/sup 15/-1/spl times/10/sup 17//cm/sup 2/, were implanted into epitaxial YBCO films with injection energies ranging from 20-180 keV, depending on the film thickness. The implanted ions do not alter the overall crystal structure of the HTS film, but do inhibit the electrical conductivity and diamagnetism. Multiple ion implantations have also been employed to achieve uniform ion distributions.<<ETX>>

A NEW RADIATIVE HEATER FOR HIGH TC THIN FILM GROWTH

The design of a new radiative heater for the growth of oxide thin films is presented. A blackbody cavity approach has been used to eliminate the large temperature variations usually observed during the growth of high Tc (HTC) superconducting thin films. Results show that this simple and inexpensive design enables one to work without the need for in situ monitoring and constant adjustment of the substrate temperature. The performance of the new heater is demonstrated by the growth of excellent quality HTC thin films.

Deoxygenation of Y-Ba-Cu-O thin films by reactive ion implantation

Thin films of YBa/sub 2/Cu/sub 3/O/sub 7/ (YBCO), grown by pulsed laser deposition, were implanted with Si/sup +/ ions at energies of 30,60, and 90 keV and at doses ranging from 1/spl times/10/sup 13/ cm/sup -2/ to 3/spl times/10/sup 11/ cm/sup -2/. X-ray diffraction techniques were used to investigate the structural dependence on implant parameters and annealing conditions, while d.c. magnetization was measured to characterize superconducting properties. By implanting only the upper portion of the film, implanted Si/sup +/ ions, near the surface, inhibit the superconductivity by removing oxygen from the bottom YBCO lattice which still retains its original crystal structure.

STABILITY OF MAGNESIUM IMPLANTED YBA2CU3O7 THIN FILMS

Magnesium ions were implanted into highly crystalline YBa2Cu3O7 (YBCO) thin films for the purpose of patterning. Films were implanted at doses corresponding to Mg contents of x=0.008, 0.02, and 0.04 in the formula YBa2(Cu1−xMgx)3O7. High temperature annealing (900 °C) of films implanted below the solubility limit was successful in obtaining single phase, Mg doped YBCO films with finite resistivities at 77 K and x-ray (005) rocking curve widths <0.15°. An electron probe microanalysis on a film patterned using Mg implantation revealed that lateral diffusion of Mg ions resulting from annealing was limited to only a few microns. The superior quality of a top layer film indicated that Mg ion implantation is suitable for multilayer patterning.

PROPERTIES OF INFINITE LAYER CA1-XSRXCUO2 FILMS OXYGEN DOPED BY ION IMPLANTATION

Infinite layer Ca1−xSrxCuO2 (CSCO) films, grown by pulsed laser deposition with x=0.66 and 0.9, were doped by implanting O+ ions with an accelerating energy of 70 keV and a dose of 3×1016 cm−2. The resistivity of the films, in the temperature range 4–200 K, decreased by over two orders of magnitude compared with the original as‐grown film. Annealing the as‐grown films in an atmosphere of O2 at 500 °C resulted in only a factor of 2 decrease in this temperature range. A magnetic anomaly resembling a diamagnetic transition was observed in the 85–90 K range in implanted films which was not observed in as‐grown films. A comparison of the properties of implanted films, before and after annealing, suggest that increased oxygen content alone is not responsible for the observed changes, and thus defect creation resulting from implantation may also play a significant role.