Esterified estrogens with and without methyltestosterone decrease arterial LDL metabolism in cynomolgus monkeys

OBJECTIVES: To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. MATERIALS AND METHODS: Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). RESULTS: Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. CONCLUSION: Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.     

Comparison of ras-p21 bound to GDP and GTP: differences in protein and ligand dynamics

This paper documents the first essential dynamics analysis of ras protein ligands and of the protein itself, showing important features of their dynamic properties. Essential dynamics analysis of 300 ps of full solvent molecular dynamics simulations revealed differences in structure and dynamics between GDP- and GTP-bound forms of H-ras-p21. Regions in the protein which exhibited a structural shift correspond to the switch regions described previously. Differences in dynamics between H-ras-p21 GDP and H-ras-p21 GTP may be related to interactions of ras with GAP and its receptor and effector. Molecular dynamics of free GDP (in the absence of protein) were performed in water for 2 ns and analysed using essential dynamics. The conformations of GDP and GTP when bound to the protein were compared with free GDP, revealing that the ligands bind to the protein in an energetically unfavourable conformation. GDP and GTP molecules from various other protein crystal structures were also analysed. These ligands adopt similar conformations to those seen in H-ras-p21.      

Development of a genetic algorithm for component placement sequence optimization in printed circuit board assembly

This paper describes the development and evaluation of a custom application exploring the use of genetic algorithms (GA) to solve a component placement sequencing problem for printed circuit board (PCB) assembly. In the assembly of PCB’s, the component placement process is often the bottleneck, and the equipment to complete component placement is often the largest capital investment. The number of components placed on a PCB can range from few to hundreds. As a result, developing an application to determine an optimal or near-optimal placement sequence can translate into reduced cycle times for the overall assembly process and reduced assembly costs. A custom application was developed to evaluate the effectiveness of using GA’s to solve the component placement sequencing problem. A designed experiment was used to determine the best representation and crossover type, crossover rate, and mutation rate to use in solving a component sequencing problem for a PCB consisting of 10 components being placed on a single-headed placement machine. Three different representations (path, ordinal, and adjacency) and six appropriate crossover types (partially mapped, ordered, cycle, classical, alternating edges, and heuristic) were evaluated at three different mutation rates and at 11 crossover rates. Two algorithm response variables, the total distance traveled by the placement head and the algorithm solution efficiency (measured as number of generations and algorithm solution time) were used to evaluate the different GA applications. The combination of representation and crossover type along with mutation rate were found to be the most significant parameters in the algorithm design. In particular, path representation with order crossover was found to produce the best solution as measured by the total distance traveled as well as the solution generation efficiency. Increasing the mutation rate led to slightly improved solutions in terms of head travel, but also resulted in increased solution time.     

Sperm storage in females of the smooth newt (Triturus v. vulgaris L.): I. Ultrastructure of the spermathecae during the breeding season

Sperm storage in cloacal spermathecae was studied in females of Triturus v. vulgaris collected early in the breeding season in southern England. Females collected in terrestrial situations, presumably unmated, were mated in the laboratory, and the ultrastructure of the transferred sperm and the spermathecae was observed at various intervals after mating. Sperm from a spermatophore cap lodged in a female's cloacal orifice can migrate into spermathecae within 1 hr after mating. Spherical structures on the axial fibers of some sperm in the cap could indicate immaturity. Disorderly clusters of sperm from the cap are still present in the cloacal chamber 12 hr after mating but are absent 24 hr after mating. During storage, sperm often are in tangled masses in the spermathecal tubules. The sperm are coated with spermathecal secretions, and some sperm nuclei were observed embedded in the spermathecal epithelium. Little evidence for spermiophagy early in the breeding season was found. During oviposition, mazes of sperm occur external to the spermathecal orifices, and sperm may be released in this condition onto eggs as they pass through the cloaca. The tangled clusters in which sperm are found from pick-up to oviposition are hypothesized as an adaptation to reduce the effectiveness of sperm competition from the ejaculates of rival males. Additional studies, using the same protocol and covering the entire cycle of sperm storage, are necessary to enable interspecific comparisons leading to phylogenetic hypotheses.     

Genetic vaccination against Coccidioides immitis: comparison of vaccine efficacy of recombinant antigen 2 and antigen 2 cDNA

Previous studies from our laboratory established that C-ASWS, an alkali-soluble, water-soluble extract from cell walls of Coccidioides immitis, protects mice against lethal challenge with this fungus. The C-ASWS extract contains a glycosylated protein, designated antigen 2 (Ag2), and a polysaccharide antigen. We recently cloned Ag2 cDNA and showed that the recombinant fusion protein elicited strong delayed-type hypersensitivity responses in immunized mice. This investigation was undertaken to determine if the recombinant Ag2 protein, expressed as an Ag2-glutathione S-transferase (GST) fusion protein, or Ag2 cDNA would protect mice against lethal challenge with C. immitis. The recombinant Ag2-GST protein protected BALB/c mice against intraperitoneal challenge with 250 arthroconidia, as assessed by a decrease in fungal CFU in tissues. The Ag2-GST-immunized mice did not show, however, an increased survival during a 30-day period postinfection. By contrast, immunization of mice with Ag2 cDNA ligated into the pVR1012 plasmid engendered protection against intraperitoneal challenge with 2,500 arthroconidia and against pulmonary challenge with 50 arthroconidia. Vaccine efficacy paralleled the development of delayed-type hypersensitivity responses to C. immitis antigen. Whereas mice vaccinated with the recombinant Ag2-GST protein did not mount footpad hypersensitivity to C-ASWS or the recombinant Ag2-GST protein, mice vaccinated with the pVR1012-Ag2 construct mounted a strong footpad hypersensitivity and their spleen cells secreted gamma interferon upon in vitro stimulation with the Ag2-containing C-ASWS extract. This is the first investigation to show that genetic immunization can protect against lethal challenge with C. immitis.