918 resultados para Fine Specificity
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Vorbesitzer: Peter Lambeck; Hiob Ludolf;
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Indexheft beiliegend
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Mathias Sanbuccellus ... quod tibi murnerius condidit ecce Thomas ...
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Five permanent cell lines were developed from Xiphophorus maculatus, X. helleri, and their hybrids using three tissue sources, including adults and embryos of different stages. To evaluate cell line gene expression for retention of either tissue-of-origin-specific or ontogenetic stage-specific characters, the activity distribution of 44 enzyme loci was determined in 11 X. maculatus tissues, and the developmental genetics of 17 enzyme loci was charted in X. helleri and in helleri x maculatus hybrids using starch gel electrophoresis. In the process, eight new loci were discovered and characterized for Xiphophorus.^ No Xiphophorus cell line showed retention of tissue-of-origin-specific or ontogenetic stage-specific enzyme gene expressional traits. Instead, gene expression was similar among the cell lines. One enzyme, adenosine deaminase (ADA) was an exception. Two adult-origin cell lines expressed ADA, whereas, three cell lines derived independently from embryos did not. ADA('-) expression of Xiphophorus embryo-derived cell lines may represent retention of an embryonic gene expressional trait. In one cell line (T(,3)) derived from 13 pooled interspecific hybrid (F(,2)) embryos, shifts with time were observed at enzyme loci polymorphic between the two species. This suggested shifts in ratios of cells of different genotypes in the population rather than unstable gene expression in one dominant cell type.^ Verification of this hypothesis was attempted by cloning the culture--seeking clones having different genetic signatures. The large number of loci electrophoretically polymorphic between the two species and whose alleles segregated independently into the 13 progeny from which this culture originated almost guaranteed the presence of different genetic signatures (lineages) in T(,3).^ Seven lineages of cells were found within T(,3), each expressing genotypes at some loci not characteristic of the expression of the culture-as-a-whole, supporting the hypothesis tested. Quantitative studies of ADA expression in the whole culture (ADA('-)) and in clones of these seven lineages suggested the predominance in T(,3) of ADA deficient cell lineages, although moderate to high ADA output clones also occurred. Thus, T(,3) has the potential to shift phenotypes from ADA('-) to ADA('+) by simply changing proportions of its constituent cell types, demonstrating that such shifts can occur in any cell culture containing cells of mixed expressional characteristics.^
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An investigation was undertaken to determine the chemical characterization of inhalable particulate matter in the Houston area, with special emphasis on source identification and apportionment of outdoor and indoor atmospheric aerosols using multivariate statistical analyses.^ Fine (<2.5 (mu)m) particle aerosol samples were collected by means of dichotomous samplers at two fixed site (Clear Lake and Sunnyside) ambient monitoring stations and one mobile monitoring van in the Houston area during June-October 1981 as part of the Houston Asthma Study. The mobile van allowed particulate sampling to take place both inside and outside of twelve homes.^ The samples collected for 12-h sampling on a 7 AM-7 PM and 7 PM-7 AM (CDT) schedule were analyzed for mass, trace elements, and two anions. Mass was determined gravimetrically. An energy-dispersive X-ray fluorescence (XRF) spectrometer was used for determination of elemental composition. Ion chromatography (IC) was used to determine sulfate and nitrate.^ Average chemical compositions of fine aerosol at each site were presented. Sulfate was found to be the largest single component in the fine fraction mass, comprising approximately 30% of the fine mass outdoors and 12% indoors, respectively.^ Principal components analysis (PCA) was applied to identify sources of aerosols and to assess the role of meteorological factors on the variation in particulate samples. The results suggested that meteorological parameters were not associated with sources of aerosol samples collected at these Houston sites.^ Source factor contributions to fine mass were calculated using a combination of PCA and stepwise multivariate regression analysis. It was found that much of the total fine mass was apparently contributed by sulfate-related aerosols. The average contributions to the fine mass coming from the sulfate-related aerosols were 56% of the Houston outdoor ambient fine particulate matter and 26% of the indoor fine particulate matter.^ Characterization of indoor aerosol in residential environments was compared with the results for outdoor aerosols. It was suggested that much of the indoor aerosol may be due to outdoor sources, but there may be important contributions from common indoor sources in the home environment such as smoking and gas cooking. ^
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This study represents a secondary analysis of the merging of emergency room visits and daily ozone and PM2.5. Although the adverse health effects of ozone and fine particulate matter have been documented in the literature, evidence regarding the health risks of these two pollutants in Harris County, Texas, is limited. Harris County (Houston) has sufficiently unique characteristics that analysis of these relationships in this setting and with the ozone and industry issues in Houston is informative. The objective of this study was to investigate the association between the joint exposure to ozone and fine particulate matter, and emergency room diagnoses of chronic obstructive pulmonary disease and cardiovascular disease in Harris County, Texas, from 2004 to 2009, with zero and one day lags. ^ The study variables were daily emergency room visits for Harris County, Texas, from 2004 to 2009, temperature, relative humidity, east wind component, north wind component, ozone, and fine particulate matter. Information about each patient's age, race, and gender was also included. The two dichotomous outcomes were emergency room visits diagnoses for chronic obstructive pulmonary disease and cardiovascular disease. Estimates of ozone and PM2.5 were interpolated using kriging, in which estimates of the two pollutants were predicted from monitoring data for every case residence zip code for every day of the six years, over 3 million estimates (one of each pollutant for each case in the database). ^ Logistic regressions were conducted to estimate odds ratios of the two outcomes. Three analyses were conducted: one for all records, another for visits during the four months of April and September of 2005 and 2009, and a third one for visits from zip codes that are close to PM2.5 monitoring stations (east area of Harris County). The last two analyses were designed to investigate special temporal and spatial characteristics of the associations. ^ The dataset included all ER visits surveyed by Safety Net from 2004 to 2009, exceeding 3 million visits for all causes. There were 95,765 COPD and 96,596 CVD cases during this six year period. A 1-μg/m3 increase in PM2.5 on the same day was associated with a 1.0% increase in the odds of chronic obstructive pulmonary disease emergency room diagnoses, a 0.4% increase in the odds of cardiovascular disease emergency room diagnoses, and a 0.2% increase in the odds of cardiovascular disease emergency room diagnoses on the following day. A 1-ppb increase in ozone was associated with a 0.1% increase in the odds of chronic obstructive pulmonary disease emergency room diagnoses on the same day. These four percentages add up to 1.7% of ER visits. That is, over the period of six years, one unit increase for both ozone and PM2.5 (joint increase), resulted in about 55,286 (3,252,102 * 0.017) extra ER visits for CVD or COPD, or 9,214 extra ER visits per year. ^ After adjustment for age, race, gender, day of the week, temperature, relative humidity, east wind component, north wind component, and wind speed, there were statistically significant associations between emergency room chronic obstructive pulmonary disease diagnosis in Harris County, Texas, with joint exposure to ozone and fine particulate matter for the same day; and between emergency room cardiovascular disease diagnosis and exposure to PM2.5 of the same day and the previous day. ^ Despite the small association between the two air pollutants and the health outcomes, this study points to important findings. Namely, the need to identify reasons for the increase of CVD and COPD ER visits over the course of the project, the statistical association between humidity (or whatever other variables for which it may serve as a surrogate) and CVD and COPD cases, and the confirmatory finding that males and blacks have higher odds for the two outcomes, as consistent with other studies. ^ An important finding of this research suggests that the number and distribution of PM2.5 monitors in Harris County - although not evenly spaced geographically—are adequate to detect significant association between exposure and the two outcomes. In addition, this study points to other potential factors that contribute to the rising incidence rates of CVD and COPD ER visits in Harris County such as population increases, patient history, life style, and other pollutants. Finally, results of validation, using a subset of the data demonstrate the robustness of the models.^
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Role of Neurogranin in the regulation of calcium binding to Calmodulin Anuja Chandrasekar, B.S Advisor: M. Neal Waxham, Ph.D The overall goal of my project was to gain a quantitative understanding of how the interaction between two proteins neurogranin (RC3) and calmodulin (CaM) alters a fundamental property of CaM. CaM, has been extensively studied for more than four decades due to its seminal role in almost all biological functions as a calcium signal transducer. Calcium signals in cardiac and neuronal cells are exquisitely precise and enable activation of some processes while down-regulating others. CaM, with its four calcium binding sites, serves as a central component of calcium signaling in these cells. It is aided in this role as a regulatory hub that differentially activates targets in response to a calcium flux by proteins that alter its calcium binding properties. Neurogranin, also known as RC3, is a member of a family of small neuronal IQ (SNIQ) domain proteins that was originally thought to play a ‘capacitive’ role by sequestering CaM until a calcium influx of sufficient intensity arrived. However, based on earlier work in our lab on neurogranin, we believe that this protein plays a more nuanced role in neurons than simply acting as a CaM buffer. We believe that neurogranin is one of the proteins which, by altering the kinetics of calcium binding allow CaM to decode a variety of signals with fine precision. To quantify the interaction between CaM, neurogranin and calcium, I used biophysical techniques and computational simulations. From my results, I conclude that neurogranin finely regulates the proportion of calcium-saturated CaM and thereby directs CaM’s target specificity.
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Ras proteins serve as crucial signaling modulators in cell proliferation through their ability to hydrolyze GTP and exist in a GTP “on” state and GTP “off” state. There are three different human Ras isoforms: H-ras, N-ras and K-ras (4A and 4B). Although their sequence identity is very high at the catalytic domain, these isoforms differ in their ability to activate different effectors and hence different signaling pathways. Much of the previous work on this topic has attributed this difference to the hyper variable region of Ras proteins, which contains most of the sequence variance among the isoforms and encodes specificity for differential distribution in the membrane. However, we hypothesize that sequence variation on lobe II of Ras catalytic domain alters dynamics and leads to differential preference for different effectors or modulators. In this work, we used all atom molecular dynamics to analyze the dynamics in the catalytic domain of H-ras and K-ras. We have also analyzed the dynamics of a transforming mutant of H-ras and K-ras and further studied the dynamics of an effectorselective mutant of H-ras. Collectively we have determined that wild type K-ras is more dynamic than H-ras and that the structure of the effector binding loop more closely resembles that of the T35S Raf-selective mutant, possibly giving us a new view and insight into the v mode of effector specificity. Furthermore we have determined that specific mutations at the same location perturb the conformational equilibrium differently in H-ras and K-ras and that an enhanced oncogenic potential may arise from different structural perturbations for each point mutation of a specific isoform.
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The neuropeptide somatostatin is a widely distributed general inhibitor of endocrine, exocrine, gastrointestinal and neural functions. The biological actions of somatostatin are initiated by interaction with high affinity, plasma membrane somatostatin receptors (sst receptors). Five sst receptor subtypes have been cloned and sequence analysis shows they are all members of the G protein coupled receptor superfamily. The G proteins play a pivotal role in sst receptor signal transduction and the specificity of somatostatin receptor-G protein coupling defines the possible range of cellular responses. However, the data for endogenous sst receptor and G protein coupling is very limited, and even when it is available, the sst receptor subtypes involved in G protein coupling and signal transduction are unknown due to the expression of multiple sst receptor subtypes in target cell lines or tissues of somatostatin.^ In an effort to characterize each individual sst receptor subtypes, antisera against unique C-terminal regions of different sst receptor subtypes have been developed in our lab. In this report, antisera made against the sst1, sst2A and sst4 receptors are characterized. They are highly specific to their corresponding receptors and efficiently immunoprecipitate the sst receptors. Using these antibodies, the cell lines expressing these sst receptor subtypes were identified with both immunoprecipitation and Western blot methods. The development of sst receptor subtype specific antibodies make it possible to determine the specificity of the sst receptor subtype and G protein coupling in target cells or tissues expressing multiple sst receptors, two questions were addressed by this thesis: (1) whether different cellular environments affect receptor subtype and G protein coupling; (2) whether different sst receptors couple to different G proteins in similar cellular environments.^ Taken together our findings, both sst1 and sst2A receptors couple with G$\alpha\sb{\rm i1},$ G$\alpha\sb{\rm i2}$ and G$\alpha\sb{\rm i3}$ in CHO cells, G$\alpha\sb{\rm i2}$ and G$\alpha\sb{\rm i3}$ in GH$\sb4$C$\sb1$ cells. Further, sst2A receptors couple with G$\alpha\sb{\rm i1},$ G$\alpha\sb{\rm i2}$ and G$\alpha\sb{\rm i3}$ in AR4-2J cells while sst4 receptors couple with G$\alpha\sb{\rm i2}$ and G$\alpha\sb{\rm i3}$ in CHO cells. Therefore, the G protein coupling of the same sst receptors in different cell lines is basically similar in that they all couple with multiple $\alpha$-subunits of the G$\rm \sb{i}$ proteins, suggesting cellular environment has little effect on receptor and G protein coupling. Moreover, different sst receptors have similar G protein coupling specificities in the same cell line, suggesting components other than receptor and G$\alpha$ subunits in the signal transduction pathways may contribute to specific functions of each sst receptor subtype. This series of experiments represent a novel approach in dissecting signal transduction pathways and may have general application in the field. Furthermore, this is the first systematic study of sst receptor subtype and G protein $\alpha$-subunit interaction in both transfected cells and in normal cell lines. The information generated will be very useful in our understanding of sst receptor signal transduction pathways and in directing future sst receptor research. ^
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The Department of Special Collections is fortunate to have a number of 19th Century illustrated bird books. These books, filled with hand-colored plates, were produced at a time when there was tremendous interest in the descriptions of new species of birds. At the same time, a new printing technique, lithography, made illustration of new species a simpler process. This combination of art and science resulted in lovely volumes like those on display.
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A prominent middle Eocene warming event is identified in Southern Ocean deep-sea cores, indicating that long-term cooling through the middle and late Eocene was not monotonic. At sites on Maud Rise and the Kerguelen Plateau, a distinct negative shift in d18O values (~1.0 per mil) is observed ca. 41.5 Ma. This excursion is interpreted as primarily a temperature signal, with a transient warming of 4°C over 600 k.y. affecting both surface and middle-bathyal deep waters in the Indian-Atlantic region of the Southern Ocean. This isotopic event is designated as the middle Eocene climatic optimum, and is interpreted to represent a significant climatic reversal in the midst of middle to late Eocene deep-sea cooling. The lack of a significant negative carbon isotope excursion, as observed during the Paleocene-Eocene thermal maximum, and the gradual rate of high-latitude warming suggest that this event was not triggered by methane hydrate dissociation. Rather, a transient rise in pCO2 levels is suspected, possibly as a result of metamorphic decarbonation in the Himalayan orogen or increased ridge/arc volcanism during the late middle Eocene.
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Insoluble residues of Late Cretaceous to Quaternary deep-sea samples from slope, trench, and oceanic plate sites south of Guatemala were examined, specifically for the distribution of clay minerals in the <2-µm fraction and of silt grains in the 20-63-µm fraction. Widespread "oceanic" particles (biogenic opal, rhyolitic glass) and their diagenetic products (smectite, clinoptilolite, heulandite) were distinguished from terrigenous material - illite, kaolinite, chlorite, plagioclase, quartz, and heavy minerals. The main results of this investigation are: (1) At Site 494 on the slope immediately adjacent to the trench, terrigenous supplies testify to a slope position of the whole sequence back to the Late Cretaceous. (2) At Site 495 on the Pacific Cocos Plate, "oceanic" and terrigenous sedimentation are clearly separated. Whereas the pelagic sedimentation prevailed in the early Miocene, terrigenous minerals appeared in the middle Miocene in the clay fraction, and in the early Pliocene in the coarse silt fraction. These terrigenous supplies are interpreted as having been transported by suspension clouds crossing the slope and even the trench. The alternative, however, an eolian transport, cannot be excluded.