Titanium and bioactive glass-ceramic coated titanium as materials for keratoprosthesis

The current problem with keratoprosthesis is the ingrowth of corneal or conjunctival epithelium into the anterior chamber. This may lead to infections and extrusion of the prosthesis as well as to the development of retroprosthetic membrane and secondary glaucoma. Glass-ceramic coated and uncoated titanium has been tested as material for the keratoprosthesis to prevent epithelial ingrowth. Twenty-two Supra-Descemet's membrane keratoprostheses were inserted in the eyes of 22 rabbits for 1, 2, 4, 8, or 12 months. The prosthesis had an optic part made of polymethylmetacrylate (PMMA). The support for the optic part and the flange of the prosthesis were made of titanium. Eleven of the prostheses were coated with glass-ceramic. The histological sections of the enucleated eyes were prepared through the central part of the cornea and the prosthesis using a cutting-grinding method. The histological analysis was made on both halves of the implants separately giving two analysis areas in each eye. All 11 titanium prostheses were retained for the time period planned. Two glass-ceramic coated prostheses were lost at 2 and 4 weeks, respectively. This was caused by difficulties at surgery due to a thick coating. These eyes were excluded from the histological analysis. No significant ingrowth of epithelium was seen in 15/18 (83%) and in 16/22 (73%) of the analysed areas of the glass-ceramic coated and titanium prostheses, respectively. Titanium appears to be a suitable material for the keratoprosthesis. The ingrowth of the epithelium may be hindered further by coating the titanium with bioactive glass-ceramic.     

Tau self-association: stabilization with a chemical cross-linker and modulation by phosphorylation and oxidation state

tau is a major component of paired helical filaments found in the neurofibrillary tangles of Alzheimer's diseased brain. However, the mechanism or mechanisms responsible for the association of tau to form these aggregates remains unknown. In this study, the role of intermolecular disulfide bonds in the formation of higher order oligomers of bovine tau and the human recombinant tau isoform T3 was examined using the chemical cross-linking agent disuccinimidylsuberate (DSS). In addition, the role of phosphorylation and oxidation state on the in vitro self-association of tau was studied using this experimental model. Stabilization of tau-tau interactions with DSS indicated that intermolecular disulfide bonds probably play a predominant role in dimer formation, but the formation of higher order oligomers of tau cannot be attributed to these bonds alone. tau-tau interactions were significantly decreased either by blocking Cys residues or by exposing the tau to a reducing (nitrogen and dithiothreitol), instead of an oxidizing, environment. tau self-association was also significantly decreased by prior phosphorylation with calcium/calmodulin-dependent protein kinase II. Phosphorylation by cyclic AMP-dependent protein kinase or dephosphorylation by alkaline phosphatase did not alter tau self-assembly. These data suggest a role for several factors that may modulate tau self-association in vivo.     

Soft tissue sarcomas in adults

Soft tissue sarcomas are relatively rare in adults, accounting for less than one percent of newly diagnosed cancers in the United States each year. However, increased physician awareness of these tumors may lead to earlier diagnosis and improved results. The five-year survival rate has been increasing, and treatment using a combination of modalities has significantly reduced the number of amputations performed. This article reviews the clinical presentation, diagnosis, pathology, and treatment of soft tissue sarcomas in adults.     

Early male initiation (time frame shift): a possible contributor to their shortened lifespan

Diosgenyl alpha-L-rhamnopyranosyl-(1--2)-[beta-glucopyranosyl-(1--3)]- beta-D-glucopyranoside (gracillin), a monodesmosidic saponin isolated from paris, dioscorea, and costacea species with promising cardiovascular and antitumor activities, was synthesized by stepwise glycosylation.     

Large-scale parallel arrays of silicon nanowires via block copolymer directed self-assembly

Extending the resolution and spatial proximity of lithographic patterning below critical dimensions of 20 nm remains a key challenge with very-large-scale integration, especially if the persistent scaling of silicon electronic devices is sustained. One approach, which relies upon the directed self-assembly of block copolymers by chemical-epitaxy, is capable of achieving high density 1?:?1 patterning with critical dimensions approaching 5 nm. Herein, we outline an integration-favourable strategy for fabricating high areal density arrays of aligned silicon nanowires by directed self-assembly of a PS-b-PMMA block copolymer nanopatterns with a L(0) (pitch) of 42 nm, on chemically pre-patterned surfaces. Parallel arrays (5 × 10(6) wires per cm) of uni-directional and isolated silicon nanowires on insulator substrates with critical dimension ranging from 15 to 19 nm were fabricated by using precision plasma etch processes; with each stage monitored by electron microscopy. This step-by-step approach provides detailed information on interfacial oxide formation at the device silicon layer, the polystyrene profile during plasma etching, final critical dimension uniformity and line edge roughness variation nanowire during processing. The resulting silicon-nanowire array devices exhibit Schottky-type behaviour and a clear field-effect. The measured values for resistivity and specific contact resistance were ((2.6 ± 1.2) × 10(5)Ωcm) and ((240 ± 80) Ωcm(2)) respectively. These values are typical for intrinsic (un-doped) silicon when contacted by high work function metal albeit counterintuitive as the resistivity of the starting wafer (～10 Ωcm) is 4 orders of magnitude lower. In essence, the nanowires are so small and consist of so few atoms, that statistically, at the original doping level each nanowire contains less than a single dopant atom and consequently exhibits the electrical behaviour of the un-doped host material. Moreover this indicates that the processing successfully avoided unintentional doping. Therefore our approach permits tuning of the device steps to contact the nanowires functionality through careful selection of the initial bulk starting material and/or by means of post processing steps e.g. thermal annealing of metal contacts to produce high performance devices. We envision that such a controllable process, combined with the precision patterning of the aligned block copolymer nanopatterns, could prolong the scaling of nanoelectronics and potentially enable the fabrication of dense, parallel arrays of multi-gate field effect transistors.     

Structurally related peptide agonist, partial agonist, and antagonist occupy a similar binding pocket within the cholecystokinin receptor. Rapid analysis using fluorescent photoaffinity labeling probes and capillary electrophoresis

The molecular basis of ligand binding to receptors provides important insights for drug development. Here, we explore domains of the cholecystokinin (CCK) receptor that are critical for ligand binding, using a novel series of fluorescent photolabile probes, receptor proteolysis, and rapid high resolution separation of peptide fragments by capillary electrophoresis. Each probe incorporated the same fluorophore and a photolabile p-benzoylphenylalanine at the amino terminus of the pharmacophoric domain (residue 24 of CCK-33) of CCK analogues representing full agonist, partial agonist, and antagonist of this receptor. Each was used to label the CCK receptor expressed on Chinese hamster ovary-CCKR cells, with the labeled domain then released by cyanogen bromide cleavage. Capillary electrophoresis with laser-induced fluorescence detection achieved an on-capillary mass sensitivity of 1.6 attomoles (10(-18) mol), with an excellent signal-to-noise ratio. Each of the biologically divergent, but structurally similar probes saturably and specifically labeled the same receptor domain, consistent with conservation of "docking" determinants. This had an apparent mass of 2.9 kDa, most consistent with the first extracellular loop domain. An additional probe having its site of covalent attachment in a different region of the probe (residue 29 of CCK-33) labeled a distinct receptor fragment with differential migration on capillary electrophoresis (third extracellular loop). Identification of the specific receptor residue(s) covalently linked to the amino-terminal probes must await further fragmentation and sequence analysis.