Showing papers by "University of Utah published in 1987"

Variable number of tandem repeat (VNTR) markers for human gene mapping

Abstract: A large collection of good genetic markers is needed to map the genes that cause human genetic diseases. Although nearly 400 polymorphic DNA markers for human chromosomes have been described, the majority have only two alleles and are thus uninformative for analysis of genetic linkage in many families. A few known marker systems, however, detect loci that respond to restriction enzyme cleavage by producing a fragment that can have many different lengths. This polymorphism is due to variation in the number of tandem repeats of a short DNA sequence. Because most individuals will be heterozygous at such loci, these markers will provide linkage information in almost all families. Ten oligomeric sequences derived from the tandem repeat regions of the myoglobin gene, the zeta-globin pseudogene, the insulin gene, and the X-gene region of hepatitis B virus, were used to develop a series of single-copy probes. These probes revealed new, highly polymorphic genetic loci whose allele sizes reflected variation in the number of tandem repeats.

Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite.

Abstract: Previous studies have shown that cytotoxic activated macrophages cause inhibition of DNA synthesis, of mitochondrial respiration, and of aconitase activity in tumor target cells. An L-arginine-dependent biochemical pathway synthesizing L-citrulline and nitrite, coupled to an effector mechanism, is now shown to cause this pattern of metabolic inhibition. Murine cytotoxic activated macrophages synthesize L-citrulline and nitrite in the presence of L-arginine but not D-arginine. L-Citrulline and nitrite biosynthesis by cytotoxic activated macrophages is inhibited by NG-monomethyl-L-arginine, which also inhibits this cytotoxic effector mechanism. This activated macrophage cytotoxic effector system is associated with L-arginine deiminase activity, and the imino nitrogen removed from the guanido group of L-arginine by the deiminase reaction subsequently undergoes oxidation to nitrite. L-Homoarginine, an alternative substrate for this deiminase, is converted to L-homocitrulline with concurrent nitrite synthesis and similar biologic effects.

The Quantitative Synthesis of Single-Subject Research Methodology and Validation

Abstract: This article describes procedures recently employed for the quantitative synthesis of single-subject research literature in special education. First, the need for objective, systematic review procedures is discussed. Second, previous approaches for quantitative evaluation of outcomes of single-case research designs are reviewed. Third, procedures employed by the present authors are outlined using examples from recent synthesis efforts. Finally, implications for future reviews of single-subject research are described.

The gene for familial polyposis coli maps to the long arm of chromosome 5.

Abstract: The inherited genetic defect in adenomatous polyposis has been localized to a small region on the long arm of chromosome 5. Sixteen DNA marker loci were used to construct a linkage map of the chromosome. When five kindreds segregating a gene for adenomatous polyposis coli were characterized with a number of the markers, significant linkage was found between one marker and the disease gene. Linkage analysis determined the location of the defective gene within a primary genetic map of chromosome 5.

Overcompensation in response to mammalian herbivory - the advantage of being eaten

Abstract: Plants of scarlet gilia, Ipomopsis aggregata, are exposed to high levels of mammalian herbivory (by mule deer, Odocoileus hemionus, and elk, Cervus elaphus) early in the season, before flowering. During this period of our study, up to 56% of all individuals experienced a 95% reduction in aboveground biomass. Browsed plants rapidly responded by producing new inflorescences and flowering within 3 wk. Unbrowsed plants produced only single inflorescences, whereas browsed plants produced multiple inflorescences. Field observations and experimental manipulations showed that plants with multiple inflorescences produced significantly greater numbers of flowers and fruits than unbrowsed individuals. Because there were no differences between browsed and unbrowsed individuals in the number of seeds produced per fruit, seed weight, subsequent germination success, and survival, browsed plants enjoyed a 2.4-fold increase in relative fitness. Consequently, there is an immediate reproductive advantage to being eaten. Und...

Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17

Abstract: Linkage analysis of 15 Utah kindreds demonstrated that a gene responsible for von Recklinghausen neurofibromatosis (NF) is located near the centromere on chromosome 17. The families also gave no evidence for heterogeneity, indicating that a significant proportion of NF cases are due to mutations at a single locus. Further genetic analysis can now refine this localization and may lead to the eventual identification and cloning of the defective gene responsible for this disorder.

Propagation and its failure in coupled systems of discrete excitable cells

Abstract: We study propagation and its failure in systems of discrete coupled excitable cells. It is shown that propagation fails when coupling is weak, but succeeds if coupling is strong enough. We use a theorem of Moser on maps of the plane to establish the existence of an infinite variety of stable standing solutions when coupling is small. We use upper and lower solution techniques and perturbation analysis to show that propagation is successful when the coupling strength is large enough. These results are applied to the cubic FitzHugh–Nagumo dynamics as well as to the more realistic Beeler–Reuter model of action potentials in myocardial cells.

Parental investment in offspring in variable environments:theoretical and empirical considerations.

Abstract: It has been argued that environmental variability favors variation in offspring size. We have examined theoretically the effects of three types of environmental heterogeneity on parental investment: spatial variation, spatial variation with density-dependent offspring fitness, and temporal variability. We concluded that environmental heterogeneity rarely favors the production of variable offspring. With spatial heterogeneity and no density dependence in fitness, a single offspring size is always optimal. Variable offspring may be favored if density-dependent fitness loss to offspring is large and if parents can control the dispersal of offspring to the appropriate habitats. If environments vary temporally, the predicted optimal parental investment strategy depends on the measure of fitness used. If the arithmetic mean of fitness is used, a single offspring size is always favored. Variable offspring sizes are sometimes selected if fitness is measured by the arithmetic mean discounted for the variance or by...

Critical wave functions and a Cantor-set spectrum of a one-dimensional quasicrystal model

Abstract: The electronic properties of a tight-binding model which possesses two types of hopping matrix element (or on-site energy) arranged in a Fibonacci sequence are studied. The wave functions are either self-similar (fractal) or chaotic and show ``critical'' (or ``exotic'') behavior. Scaling analysis for the self-similar wave functions at the center of the band and also at the edge of the band is performed. The energy spectrum is a Cantor set with zero Lebesque measure. The density of states is singularly concentrated with an index ${\ensuremath{\alpha}}_{E}$ which takes a value in the range [${\ensuremath{\alpha}}_{E}^{\mathrm{min}}$,${\ensuremath{\alpha}}_{E}^{\mathrm{max}}$]. The fractal dimensions f(${\ensuremath{\alpha}}_{E}$) of these singularities in the Cantor set are calculated. This function f(${\ensuremath{\alpha}}_{E}$) represents the global scaling properties of the Cantor-set spectrum.

Thermo-sensitive polymers as on-off switches for drug release

Abstract: Liberation de l'indomethacine contenue dans le copolymere N-isopropylacrylamide-methacrylate de butyle

Localization of optics: Quasiperiodic media.

Abstract: An experiment to probe the (quasi)localization of the photon is proposed, in which optical layers are constructed following the Fibonacci sequence. The transmission coefficient has a rich structure as a function of the wavelength of light and, in fact, is multifractal. For particular wavelengths for which the resonance condition is satisfied, the light propagation has scaling with respect to the number of layers, as well as an interesting fluctuation.

Concepts and comparisons in multidimensional separation

Abstract: Multidimensional separation methodology provides a mechanism for a very substantial increase in the resolving power of chromatographic and related systems. After defining the conditions required for multidimensional separation and reviewing the origin of its high resolving power, a comparison is drawn between the two principal kinds of multidimensional systems, represented by continuous two-dimensional operation and coupled column assemblies. It is shown that their roles are complementary. The two-dimensional system gives a broad powerful overview of a sample while the coupled column system can be used flexibly to magnify and resolve selected regions of the sample space.

Ubiquitin-Mediated Pathways for Intracellular Proteolysis

Abstract: Ubiquitination is one of several ways in which cells modify their proteins. As for phosphorylation or acetylation, there are distinct enzymes for adding and removing Ub from the surfaces of protein substrates. The dynamic equilibration of Ub with cellular proteins is also typical of most posttranslational modifications. Ubiquitination differs, however, in that the added group is large compared to acetate or phosphate. Its size must provide great potential for recognition by other cellular proteins. Ub may be the cell's reversible cross-linking reagent, covalently bound to protein substrates at one end and noncovalently associated with various Ub binding proteins at the other. It is likely that one ubiquitin binding protein is a component of the 26S ATP-dependent protease. The presence of Ub on histones and on the lymphocyte homing receptor suggests that ubiquitination does not serve exclusively to mark proteins for degradation. There are probably various ubiquitin binding proteins since Ub appears to be a multifunctional protein that affects chromatin structure, intracellular proteolysis, cellular interactions, and the stress response. This abundant protein may serve as an intracellular barometer whose distribution among several pools regulates a variety of processes.

Neutral and Charged Biradicals, Zwitterions, Funnels in S1, and Proton Translocation: Their Role in Photochemistry, Photophysics, and Vision

Abstract: A knowledge of the geometries at which excited molecules return to the electronic ground state (S0) is essential for the understanding of the structures of photoproducts. Particularly good candidates are geometries corresponding to local minima on the S1 (lowest excited singlet) and T1(lowest triplet) surfaces, as well as S0–S1 conical intersections (funnels). Given sufficient effort, such geometries can nowadays be found numerically for small enough molecules. Still, it is interesting to ask whether more approximate, but also more general, statements can be made concerning the geometries at which the S0 and S1 surfaces closely approach each other. Since many of these are biradicaloid geometries, it is logical to examine the properties of biradicals and related species at some length. After reviewing the two-electron two-orbital model for molecules at biradicaloid geometries, we formulate the conditions under which the S0 and S1 surfaces touch. The results obtained for the simple model are supported by ab initio large-scale configuration interaction (CI) calculations for the twisting of ethylene in the polarizing field of a positive charge and for the twisting of charged double bonds and π-donor-to-π-acceptor single bonds, and by similar calculations for “push-pull” perturbed cyclobutadienes, some of which are predicted to have nearly degenerate S0, S1, and T1 states. The likely consequences of these results for the detailed description of the mechanisms of cis-trans isomerization, the formation of twisted internal charge-transfer (TICT) states, proton translocation, and possibly of the initial step in vision, as well as for the understanding of the regiospecificity of singlet photocycloaddition, are summarized.

Reproductive success, spontaneous embryo abortion, and genetic load in flowering plants.

Abstract: Reproductive success is divided into two phases: preemergent (the number of viable seeds that enter the ambient environment) and postemergent (the percentage of progeny that survive to reproduce). We studied preemergent reproductive success (PERS) in flowering plants by measuring the fruit/flower (Fr/Fl) ratio and the seed/ovule (S/O) ratio in a number of species of outcrossing and inbreeding plants, where PERS=the product of (Fr/Fl) and (S/O). In order to determine the influence of the ambient environment (including resource availability) we studied pairs of outcrossing and inbreeding species occurring in the same habitat. Among outcrossing species PERS averaged about 22%, whereas in inbreeding species the average was approximately 90%. The progeny/zygote (P/Z) ratio was studied in hand-pollinated populations in Epilobium angustifolium (a strongly outcrossing species) from populations in Oregon and Utah, by direct observation of embryogenesis at twoday intervals throughout the course of seed development. The P/Z ratio in both populations averaged near 30%, and the developing embryos showed a surprising array of abnormalities that resulted in embryo death. During early development >95% of the ovules had normally developing globular embryos, but beginning with differentiation (cotyledon formation) about 70% of the original globular embryos aborted during the course of embryogenesis and seed development. The clustering of developmental lethals during peroids of major differentiation events parallels the animal model of development. We found little evidence that PERS was limited by the ambient environment (including resource availability), pollination, or factors associated with the inbreeding habit. Instead, PERS was found to be inextricably linked to outcrossing plants, whose breeding systems promote genetic variability. The high incidence of developmental lethals in E. angustifolium and the resulting low P/Z ratio (ca. 30%) is attributed to genetic load (any lethal mutation or allelic combination) possibly working in combination with developmental selection (interovarian competition among genetically diverse embryos). Examples of maternally controlled, fixed patterns of ovule abortion with respect to position or number are discussed. However, we found no need to employ “female choice” as a hypothesis to explain our results for the extensive, seemingly random patterns of embryo abortion in E. angustifolium and other outcrossing species. A more parsimonious, mechanistic explanation based on genetic load-developmental selection is sufficient to account for the differential survivorship of embryos. Likewise, the traditional concept of a positive growth regulator feedback system based on the number of surviving ovules in an ovary can account for subsequent fruit survivorship.

A stable finite element solution for two-dimensional magnetotelluric modelling

Abstract: Summary. We report herein on a finite element algorithm for 2-D magnetotelluric modelling which solves directly for secondary variations in the field parallel to strike, plus the subsequent vertical and transverse auxiliary fields, for both transverse electric and transverse magnetic modes. The governing Helmholtz equations for the secondary fields along strike are the same as those for total field algorithms with the addition of source terms involving the primary fields and the conductivity difference between the body and the host. Our approach has overcome a difficulty with numerical accuracy at low frequencies observed in total field solutions with 32-bit arithmetic far the transverse magnetic mode especially, but also for the transverse electric mode. Matrix ill-conditioning, which affects total field solutions, increases with the number of element rows with the square of the maximum element aspect ratio and with the inverse of frequency. In the secondary formulation, the field along strike and the auxiliary fields do not need to be extracted in the face of an approximately computed primary field which increasingly dominates the total field solution towards low frequencies. In addition to low-frequency stability, the absolute accuracy of our algorithm is verified by comparison with the TM and the TE mode analytic responses of a segmented overburden model.

Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom.

Abstract: The omega-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, omega-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences show significant differences from omega-conotoxins from Conus geographus. Total synthesis of omega-conotoxin MVIIA was achieved, and biologically active radiolabeled toxin was produced by iodination. Although omega-conotoxins from C. geographus (GVIA) and C. magus (MVIIA) appear to compete for the same sites in mammalian brain, in amphibian brain the high-affinity binding of omega-conotoxin MVIIA has narrower specificity. In this system, it is demonstrated that a combination of two omega-conotoxins can be used for biochemically defining receptor subtypes and suggested that these correspond to subtypes of neuronal Ca2+ channels.

Alyawara Site Structure and Its Archaeological Implications

Abstract: Ethnoarchaeological research has shown that the assumptions formerly guiding the investigation of hunter-gatherer site structure are invalid, at least as general rules. Further research is now required to identify the determinants of site structure and assess their effect. Here I describe those aspects of Alyawara behavior that shape site structure at residential base camps. I then compare certain features of the Alyawara case with those of the !Kung and the Nunamiut. I tentatively infer that most of the variability in site structure in these cases is a function of differences in the degree of reliance on food storage, seasonal variation in weather, household population size, and the length of time activity areas are in use. Predator pressure and the relative importance of interhousehold food sharing may also be involved. The apparent importance of food storage suggests that variation in site structure may parallel Binford's (1980) forager-collector continuum. Further research is required to determine if this is so, and whether other aspects of behavior also affect site structure. These observations have important implications for the conduct of archaeological research, especially for the spatial scales at which analyses of site structure are undertaken, and for the sizes of refuse items considered in such analyses.

Improved convergence analysis of stochastic gradient adaptive filters using the sign algorithm

Abstract: Convergence analysis of stochastic gradient adaptive filters using the sign algorithm is presented in this paper. The methods of analysis currently available in literature assume that the input signals to the filter are white. This restriction is removed for Gaussian signals in our analysis. Expressions for the second moment of the coefficient vector and the steady-state error power are also derived. Simulation results are presented, and the theoretical and empirical curves show a very good match.

Plasma protein adsorption: the big twelve.

Abstract: We have discussed the general principles of protein adsorption at solid-liquid interfaces from single component and multicomponent solutions, based on qualitative kinetic models that include mass transport considerations, initial interaction energies, surface-dependent conformational changes, and possible desorption processes. We have surveyed plasma protein components greater than one milligram per milliliter in concentration, which we call "The Big Twelve." We considered their size, concentration, diffusion coefficient, structure and function, and methods of estimating their "surface denaturability" by using bulk solution measures of denaturation and conformational change. We have suggested that the role of the carbohydrate moieties in plasma proteins may have some bearing on their adsorption properties. We further suggest that lipoproteins, because of their lipid phase transition and conformational lability at body temperature, may tend to dominate the adsorption process, particularly on mobile elastomeric polymer surfaces. We suggest that detailed consideration of the structure and characteristics of each of the proteins involved is necessary in order to begin to understand plasma adsorption processes. Detailed characterization and understanding of the solid surface in the aqueous and protein environments are also required.

Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis.

Abstract: Genetically hypotransferrinemic mice accumulate iron in the liver and pancreas. A similar pattern of tissue iron accumulation occurs in humans with hereditary hemochromatosis. In both disorders, there is a decreased plasma concentration of apotransferrin. To test the hypothesis that nontransferrin-bound iron exists and is cleared by the parenchymal tissues, the tissue distribution of 59Fe was studied in animals lacking apotransferrin. Two groups of animals were used: normal rats and mice whose transferrin had been saturated by an intravenous injection of nonradiolabeled iron, and mice with congenital hypotransferrinemia. In control animals, injected 59Fe was found primarily in the bone marrow and spleen. In the transferrin iron-saturated animals, injected 59Fe accumulated in the liver and pancreas. Gastrointestinally absorbed iron in hypotransferrinemic or transferrin iron-saturated mice was deposited in the liver. This indicates that newly absorbed iron is released from mucosal cells not bound to transferrin. Clearance studies demonstrated that transferrin-bound 59Fe was removed from the circulation of rats with a half-time of 50 min. In transferrin iron-saturated animals, injected 59Fe was removed with a half-time of less than 30 s. Analysis of the distribution of 59Fe in serum samples by polyacrylamide gel electrophoresis demonstrated the presence of 59Fe not bound to transferrin. These results demonstrate the existence of and an uptake system for non-transferrin-bound iron. These observations support the hypothesis that parenchymal iron overload is a consequence of reduced concentrations of apotransferrin.