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Biomedical subjects

David H Brown

Publications and source records attributed to David H Brown.

8 recordsLinked to original sources

Azolium-linked cyclophanes: a comprehensive examination of conformations by 1H NMR spectroscopy and structural studies.

The synthesis and characterization of a series of azolium-linked cyclophanes are reported. The cyclophanes consist of two azolium groups (17 examples) or three imidazolium groups (1 example) linked to two benzenoid units (benzene, naphthalene, p-xylene, mesitylene, 1,2,3,4- and 1,2,4,5-tetramethylbenzene, 2,6-pyridine, and p-tert-butylphenol) via methylene groups. Cyclophanes containing ortho-, meta-, and para-substitution patterns in the benzenoid units were examined. The conformations of the cyclophanes were examined in solution by variable-temperature NMR studies and in the solid state by crystallographic studies. The p-cyclophanes and mesitylene-based m- and o/m-cyclophanes are rigid on the NMR time scale, as indicated by sharp (1)H NMR spectra at all accessible temperatures. The non-mesitylene-based m-cyclophanes and the o-cyclophanes are fluxional on the NMR time scale at high temperatures, but in most cases, specific conformations can be "frozen out" at low temperatures. Many structures deduced from solution studies were consistent with those in the solid state.

Journal Article↗

Dinuclear N-heterocyclic carbene complexes of silver(I), derived from imidazolium-linked cyclophanes.

The synthesis of four new silver complexes of bidentate N-heterocyclic carbenes, derived from imidazolium-linked cyclophanes, has been achieved via a simple complexation reaction of the imidazolium-linked cyclophanes with the basic metal source Ag(2)O. The cyclophane structures contain two imidazolyl links between ortho-, meta- and mixed ortho/meta-substituted aromatic rings. The new silver carbene systems are thermally stable and have been characterised by NMR spectroscopy and X-ray crystallography. Three of the complexes have a dimeric structure of the form [L(2)Ag(2)](2+) in the solid state that is rigid on the NMR timescale in solution. The fourth complex has a neutral structure of the form [L(AgBr)(2)], the NMR studies suggesting some lability of the L-Ag bonding in solution.

Journal Article↗

Solid-supported cross-coupling catalysts derived from homogeneous nickel and palladium coordination complexes.

Solid-supported catalysts derived from homogeneous nickel(II) and palladium(II) non-symmetrical salen-type coordination complexes have been prepared and shown to be effective in the heterogeneous catalysis of carbon-carbon cross-coupling reactions. The nickel catalyst has been used in room-temperature Tamao-Kumada-Corriu reactions and the palladium catalyst in the Heck reaction at elevated temperatures. The complexes were prepared by improved methods and characterised by spectroscopic techniques. Comparisons between the solid-supported catalysts and their homogeneous analogues are reported. The single-crystal structure determination of the nickel and palladium complexes [M(salenac-OH)][M = Ni, Pd; salenac-OH = 9-(2',4'-dihydroxyphenyl)-5,8-diaza-4-methylnona-2,4,8-trienato](2-)] is reported.

Journal Article↗

The effects of disease dispersal and host clustering on the epidemic threshold in plants.

For an epidemic to occur in a closed population, the transmission rate must be above a threshold level. In plant populations, the threshold depends not only on host density, but on the distribution of hosts in space. This paper presents an alternative analysis of a previously presented stochastic model for an epidemic in continuous space (Bolker, 1999, Bull. Math. Biol. 61, 849-874). A variety of moment closures are investigated to determine the dependence of the epidemic threshold on host spatial distribution and pathogen dispersal. Local correlations that arise during the early phase of the outbreak determine whether a true global epidemic will occur.

Disease Transmission, Infectious↗

Modeling direct positive feedback between predators and prey.

Predators can have positive impacts on their prey through such mechanisms as nutrient mineralization and prey transport. These positive feedbacks have the potential to change predictions based on food web theory, such as the assertion that enrichment is destabilizing. We present a model of a simple food web, consisting of a resource, a consumer, and its predator. We assume that the predator has a direct positive effect on the consumer, by increasing the rate at which the consumer acquires resources. We consider two cases: the feedback strength is a saturating function of predator density, or it is proportional to the encounter rate between predators and prey. In both cases, the positive feedback is stabilizing, delaying or preventing the onset of oscillations due to enrichment. Positive feedback can introduce an Allee effect for the predator population, yielding multiple stable equilibria. Strong positive feedback can yield counterintuitive results such as a transient increase in consumer density following the introduction of predators, and a decrease in the resource pool following enrichment.

Animals↗

Resistance may be futile: dispersal scales and selection for disease resistance in competing plants.

If a host species shares a pathogen with competing species, the disease may provide a net benefit. Selection for resistance will depend on the trade-off between the damage done by the disease and the positive effects resulting from infection of competitors. This paper presents a simple, spatially explicit model of a plant that shares a disease with a superior competitor. The phenotypic evolution of cost-free resistance is studied by using the method of pair approximation to analyse the small-scale spatial structure of the interacting populations. Selection favors lower resistance when disease transmission is spatially local and the damage to the competitor is sufficient to outweigh the direct effects of infection. This suggests that local spatial structure may be critical in determining the coevolution of host-host-pathogen systems.

Competitive Behavior↗

A novel technique for ureteral catheterization and/or retrograde ureteroscopy after cross-trigonal ureteral reimplantation.

PURPOSE: A criticism of the Cohen cross-trigonal reimplantation is the potential difficulty of retrograde access to the ureter. With the advent of modern endourological equipment, we devised a novel technique that obviates the aforementioned difficulty and permits even retrograde ureteroscopy. MATERIALS AND METHODS: Cystoscopy is performed and a curved tip vascular access catheter is directed towards the ureteral orifice. An angle tipped glide wire with a torque device attached is passed through the catheter and directed into the orifice. The combination of the curved catheter and angled glide wire permits passage of the wire in an axis perpendicular to that of the cystoscope. Once the glide wire has been passed into the proximal ureter it is exchanged for a super stiff guide wire. The latter literally straightens the ureter permitting direct retrograde passage of a catheter, stent or rigid ureteroscope. RESULTS: This technique was successful in 6 children. Of the patients 4 underwent retrograde ureteroscopy with stone extraction, 1 underwent retrograde studies followed by stent insertion and 1 underwent retrograde catheterization alone for radiographic studies. CONCLUSIONS: It is distinctly uncommon to have to access a ureter in a retrograde fashion after cross-trigonal reimplantation. However, when required the technique described reliably permits retrograde access and should dispel fears of long-term consequences of the Cohen ureteral reimplantation.

Adolescent↗

Eight novel mutations in the HEXA gene.

PURPOSE: To characterize novel mutations in the HEXA gene (alpha-subunit beta-hexosaminidase A). METHODS: Subjects included participants in the California Tay-Sachs disease prevention program. DNA samples from 49 subjects (47 enzymatically defined carriers and 2 disease afflicted) who were negative for the four common disease-associated and the two pseudodeficient mutations, were subjected to single-strand conformation polymorphism (SSCP) analysis over 14 exons. RESULTS: Targeted sequencing of the 39 electrophoretic variants from SSCP analysis revealed eight novel and deleterious mutations and 31 with previously described mutations. Six novel mutations were found in non-Jewish carriers, and two were found in two patients with infantile Tay-Sachs disease. CONCLUSION: Identification of these eight novel mutations provides additional insight to the mutational spectrum for the HEXA gene. Furthermore, this knowledge should enhance diagnosis and prognosis for Tay-Sachs disease, carrier identification, and fundamental studies in structure/function relationships between this gene and its enzymatic product.

DNA Mutational Analysis↗