• The influence of mechanical stratigraphy on the development of detachment folds and associated mesoscopic structures: an example from the Lisburne group carbonates, northeastern Brooks Range, Alaska

      Hayes, Michael Robert (2004-08)
      The mechanical properties of individual stratigraphic layers in a multi-layer sequence of sedimentary rock influence the deformational response before, during, and after fold development. To demonstrate this, the mechanical character of stratigraphic layers and mesoscopic deformational structures within individual stratigraphic layers were documented in two well-exposed outcrop-scale detachment folds in the Lisburne Group carbonates, northeastern Brooks Range, Alaska. Fold geometry and fold-related mesoscopic structures indicate that flexural slip and flexural flow are the operative fold mechanisms until a critical interlimb angle of 90° is reached, after which homogenous flattening occurs. Changes in bed thicknesses due to homogenous flattening alter the overall fold geometry. Lithostratigraphic unit boundaries do not always coincide with mechanical unit boundaries. Thin shale layers lower the bedding interface strength and commonly form flexural slip horizons that define mechanical unit boundaries. As fold shortening progresses, slip horizon spacing is interpreted to decrease, causing mechanical unit thickness to decrease. Newly forming mechanical boundaries alter the conditions of deformation, which change the overall fold dynamics. Surveyed fracture sets reveal the influence of lithology, mechanical unit thickness, anisotropy, and structural position on fracture distribution within individual mechanical units. Fracture densities vary from set to set and unit to unit due to structural and stratigraphic controls within these folds.
    • Influence of permafrost extent on photochemical reactivity, functional group composition, and geochemical cycling of a subarctic discontinuous permafrost Alaskan watershed

      Gagné, Kristin R.; Guerard, Jennifer J.; Simpson, William; Trainor, Thomas P.; Jones, Jeremy (2020-05)
      Sub-Arctic Alaskan boreal forests are currently extremely susceptible to permafrost thaw caused by increases in atmospheric temperatures in the region. Upon thaw, permafrost soil organic matter can leach out organic matter, nitrogen, and metals. It is important to observe the effects the leaching of permafrost may have on photoreactivity, functional group composition, and metal introduction. Photoproduced reactive oxygen species may affect metal fate and transport through mechanisms such as the photo-Fenton reaction. Functional group analysis allows for differences in natural organic matter source and ability to complex metals throughout a watershed. Additionally, permafrost soils may have the ability to leach in metals through lateral flow of surface waters as observed in other studies. These metals could then complex to organic matter and alter the geochemical cycling within the watershed. Organic matter is a nutrient source, and metals (e.g., As) may increase the toxicity of surface waters through the thaw of permafrost. The influx of sequestered organic matter and metals to surface waters has the potential to drastically alter ecosystem processes. This study observes how permafrost leaching affects water composition, including its overall photoreactivity and functional group composition. The data obtained was then used to observe and deduce conclusions on how permafrost thaw influences surface water photoreactivity and functional group composition. Finally, trace metal analysis was conducted on a whole watershed scale over three years to observe how permafrost influences the geochemical composition of three main thermokarst surface waters with varying degrees of permafrost degradation. Overall, permafrost was determined to be heterogeneous and highly photoreactive both inter- and intra- watershed. Additionally, the functional group composition of surface waters influenced by permafrost thaw was different between summer and winter, indicating that winter is an important period to sample. Due to this change in functional group composition, the photoreactivity of winter samples was higher than summer with regard to the production of reactive oxygen species. Metal concentrations also increased during the winter for lakes identified to be undergoing active permafrost thaw. Finally, this case study found that metal concentration data combined with optical indices provided important information for resolving the possible extent of permafrost beneath thermokarst lakes.
    • The influence of phenocrysts in silicic magma degassing

      deGraffenried, Rebecca; Larsen, Jessica; Freymueller, Jeffrey; Izbekov, Pavel (2017-08)
      Understanding the degassing process in magma is an important goal because of the first-order control it exerts on determining eruption style. Degassing in high viscosity magmas is of particular interest since these magmas tend to erupt explosively. However, the role of phenocrysts in the degassing process is still poorly constrained, though recent data indicate that the presence of phenocrysts should promote permeability development at lower porosities than in crystal-free magmas. This study specifically examined the effect of phenocrysts in a rhyolitic magma, but the results can also be applied to crystal-rich intermediate magmas that have rhyolitic matrix melts. Isothermal decompression experiments were conducted using powdered rhyolite (76 wt. % SiO2) and seeded with corundum (Al2O3) crystals to approximate magmas with 20 and 40 vol. % phenocrysts. Experiments were saturated at 900˚C and 110 MPa then continuously decompressed to final pressures between 75 and 15 MPa. Percolation threshold was determined by measuring permeability on a benchtop permeameter and measuring porosity from reflected light images. Additionally, vesicle structure was assessed by measuring pore throat radii from back-scattered electron images and plotting bubble size distributions. Finally, degassing state was checked by measuring dissolved water contents in the glass with Fourier Transform Infrared (FTIR) spectroscopy analyses. The addition of at least 20 vol. % phenocrysts resulted in a decrease in percolation threshold from 70-80 vol. % porosity in crystal-free rhyolites to 55 vol. % porosity. Bubble size distribution patterns indicate that coalescence was more widespread as final pressure decreased and crystal content increased. Minimum pore throat radii in the 40 vol. % phenocryst series were larger than in the 20 vol.% phenocryst and crystal-free series. The dissolved water measurements indicate that these experiments degassed in equilibrium even at the fast decompression rate of 0.25 MPa/s. Calculations of the magnitude of outgassing from the decreased percolation threshold and timescales of pressure dissipation indicate that the presence of phenocrysts plays a role in the effusive-explosive cyclicity of Vulcanian-style eruptions.
    • Insights into deep structure and evolution of Alaska based on a decade of observations of shear wave splitting and mantle flow

      Bellesiles, Anna K. (2011-05)
      This thesis covers shear wave splitting results from a decade of temporary networks deployed throughout Alaska. The analysis and interpretation of data from the MOOS (Multidiscipline Observations Of Subduction) and ARCTIC (Alaska Receiving Cross Transect for the Inner Core) PASSCAL (Program for Array Seismic Studies of the Continental Lithosphere) deployments, combined with the previously published BEAAR (Broadband Experiment Across the Alaska Range) results provide anisotropy and flow observations across the state. In south central Alaska, a region dominated by the subduction of the Pacific plate under the North American plate, fast directions are dominantly in the direction of convergence (NNW-SSE), or trench-normal. This is either due to entrained flow below the subducting portion of the Yakutat block, or anisotropy within the block itself. Farther north above the mantle wedge the shear wave splitting results are dominated by fast directions along the strike of the subducting slab (NE-SW), due to along strike flow within the mantle wedge. North of the mantle wedge, fast directions transition into a more NNE to SSW orientation which is the Brooks Range and North slope are in the direction of absolute plate motion.
    • Inter-individual variation in gene expression in torpid and interbout euthermic Arctic ground squirrels

      Burman, Adlai Max (2006-12)
      Alaskan Arctic ground squirrels, Spermophilus paryii, hibernate about seven months per year. During two-week torpor periods, respiration, circulation, metabolism, and catabolism are dramatically decreased, except for brief periods of interbout euthermia. These divergent hibernation states provide a particularly compelling model for variance-based studies of global gene expression. A guiding hypothesis in this Thesis is that Arctic ground squirrels exit interbout euthermia and enter torpor with an invariant metabolic scaffolding of various metabolites that are erected to serve as a ready metabalome for the challenges of the next brief return to euthermia. To develop this hypothesis further, I performed an exploratory data analysis of high-density mouse cDNA micro arrays cross-hybridized with Arctic ground squirrel mRNA to measure transcriptomes in brown adipose, skeletal muscle, and liver tissues. The results revealed that variation in transcript expression profiles were tissue specific and may reflect the degree to which tissues are active during hibernation. These results are encouraging. They justify a more thorough evaluation of the utility of using global variation in transcript expression patterns. In combination with a priori biological knowledge, these patterns will guide future studies into more detailed analyses of hibernation-state dependent and functionally relevant transcripts.
    • The interaction of Io and the Jovian magnetic field: Io's Alfven wings and particle acceleration

      Dols, Vincent (2001-08)
      Conditions for the formation of an electric field along the field lines of Jupiter crossing the satellite Io are investigated by examining the properties of Io's Alfven wave. A three-dimensional self-consistent MHD model, using a simplified magnetosphere description, illustrates the formation of this electric field and of Io's related auroral emission in the Jovian ionosphere. The Alfven wing properties between Io and Jupiter are studied with a one-dimensional MHD model and a realistic magnetosphere. Any change in the Io/Jupiter system affects the structure of the Alfven wing and likely affects the structure of Io's auroral emissions. This emission is likely structured in multi-spots and the angle between the first spot and the instantaneous projection of Io is less than 3°. In the limited context of the 1D approximation, the acceleration mechanism is expected close to Jupiter.
    • Interaction of two tributary glacier branches and implications for surge behavior

      Knowles, Christopher P.; Truffer, Martin; Larsen, Chris; Newman, David; Wackerbauer, Renate (2018-05)
      A glacier surge is a dynamic phenomenon where the glacier after a long period of quiescence, increases its velocities by up to two orders of magnitude. These surges tend to have complex interactions with tributaries, yet the role of these tributary interactions towards glacier surging has yet to be fully investigated. In this work we construct a synthetic glacier with an adjustable tributary intersection angle to study tributary interaction with the trunk glacier. The geometry we choose is loosely based on the main trunk and tributary interaction of Black Rapids Glacier, AK, USA, which last surged in 1936-1937. We investigate surface elevations, medial moraine locations, and erosive power at the bed of the glacier in response to our adjustable domain and relative flux. A nonlinear relationship between tributary flux and surface elevations is found that indicates flow restrictions can occur with geometries like Black Rapids Glacier. These flow restrictions cause increased ice thicknesses up-glacier which can lead to surges via increased stresses.
    • Intermittent hypercapnia induces long-lasting ventilatory plasticity to enhance CO₂ responsiveness to overcome dysfunction

      Mosher, Bryan Patrick; Harris, Michael B.; Taylor, Barbara E.; Hueffer, Karsten; Edmonds, Brian W. (2014-05)
      The ability of the brain to detect (central CO₂ chemosensitivity) and respond to (central CO₂ chemoresponsiveness) changes in tissue CO₂/pH, is a homeostatic process essential for mammalian life. Dysfunction of the serotonin (5-HT) mechanisms compromises ventilator CO₂ chemosensitivity/responsiveness and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). The laboratory of Dr. Michael Harris has shown medullary raphe' contributions to central chemosensitivity involving both 5-HT- and y-aminobutyric acid (GABA)-mediated mechanisms. I tested the hypothesis that postnatal exposure to mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of bicuculline- and saclofen-sensitive mechanisms (GABAA and GABAB receptor antagonists respectively). Rats were exposed to IHc-pretreatment (8 cycles of 5 % CO₂) for 5 days beginning at postnatal day 12 (P12). I subsequently assessed CO₂ responsiveness using an in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. In addition, IHc-pretreatment effectiveness was tested for its ability to overcome dysfunction in the CO₂ responsiveness induced by a dietary tryptophan restriction. This dysfunctional CO₂ responsiveness has been suggested to arise from a chronic, partial 5-HT reduction imparted by the dietary restriction. Results show IHc-pretreatment induced plasticity sufficient for CO₂ responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. CO₂ responsiveness following IHc-pretreatment was absent if ketanserin was combined with bicuculline and saclofen, indicating that the plasticity was dependent upon bicuculline- and saclofen-sensitive mechanisms. IHc-induced plasticity was also capable of overcoming the ventilatory defects associated with maternal dietary restriction. Duration of IHc-induced plasticity was also investigated and found to last far into life (up to P65). Furthermore, I performed experiments to investigate if IHc-induced plasticity was more robust at a specific developmental period. No such critical period was identified as IHc-pretreatment induced robust respiratory plasticity when administered at all developmental periods tested (P12-16, P21-25 and P36-40). I propose that IHc-induced plasticity may be able to reduce the severity of reflex dysfunctions underlying pathologies such as SIDS.
    • Interpretation of radarsat SAR scenes of Sagwon Alaska, to establish temporal, spatial and physical active layer behavior

      Lovick, Joseph Thomas (2003-05)
      Radarsat SAR images of the Kuparuk Basin in North Alaska can be used to describe the timing and characteristics of the seasonal freeze-thaw cycle and the spatial distribution of two types of Arctic Tundra. The freezing of the ground surface; decreases backscatter brightness by 3dB allowing the date of freeze-up and thaw to be established. Using Empirical Orthogonal Functions on amplitude images allows the subtle change in the brightness (during winter) of different tundra types to be enhanced, which provides a technique for discriminating between areas of Moist Acidic Tundra and Moist Non-acidic Tundra. The sand to clay ratio affects the backscatter properties of frozen soil and is inferred to cause this brightness difference. Coherence images show the dynamic nature of Arctic tundra, and low coherence limits the applicability of interferometric techniques to describe active layer heave, however, preliminary results show promise in the application of a differential interferometric technique.
    • Intrinsic Markers In Avian Populations: Explorations In Stable Isotopes, Contaminants, And Genetics

      Rocque, Deborah Anne; Winker, Kevin; Duffy, Lawrence K.; Ben-David, Merav; Barry, Ronald P. (2003)
      This research outlines the diversity of questions that intrinsic markers have the potential to answer and demonstrates some of these marker's limitations and successes. To test the working hypothesis that feathers grown on different continents have significantly different stable isotope ratios in commonly used markers, I analyzed stable isotopes in two generations of feathers from three species of birds that breed at high latitudes and winter on different continents. As expected, significant differences in stable isotope ratios were detected between summer- and winter-grown feathers in both plover species (Pluvialis fulva and P. domininca). However, no differences were found between the two groups of winter-grown plover feathers, despite being grown on different continents. Similarly, no differences were detected in isotope values between summer- and winter-grown feathers in northern wheatears (Oenanthe oenanthe). Large variances in isotope ratios limited the percentage of feathers correctly assigned to their origins to 41%. Atmospheric transport has been identified as the source of pollutants in several arctic ecosystems and has the potential to severely impact high-latitude populations. To determine whether long-range atmospheric transport, point sources, or migratory prey were sources of contaminants in the North Pacific, birds from two trophic levels were sampled across the longitudinal transect of the Aleutian Archipelago. Carbon isotope ratios differed among islands, thereby linking birds to island food webs and ruling out contaminant transfer through migratory prey. Patterns in some PCB congeners indicated local point sources, but significant west-to-east declines in contaminant concentrations for the majority of detected organochlorines provided evidence of long-range transport. Linking individuals to source populations using intrinsic markers has only been successful at broad scales. To determine whether increased resolution among populations could be achieved by merging multiple intrinsic marker classes, a new analytical procedure was developed. Discrete and continuous markers were combined to evaluate a Bayesian method of assignment across marker classes. For three datasets, two real and one simulated, the percentage of individuals assigned to correct source populations increased with the addition of markers and marker classes. In all cases, the maximum number of individuals was correctly assigned when all marker classes were combined.
    • Invasive plants and pollination of Alaskan berry species: integrating ecology and education

      Spellman, Katie Villano; Mulder, Christa; Wagner, Diane; McGuire, A. David; Conner, Laura; Carlson, Matthew (2015-05)
      A rapidly changing climate and human disturbance patterns have accelerated the spread of invasive plants species in Alaska. Non-native plant invasions can disrupt pollinator services to native plants and have the potential to impact the pollination and fruit set in berry species important for subsistence harvest. My dissertation aims to address the dual need for greater understanding of the impacts of invasive plants on pollination of berry species in boreal ecosystems and the need for research on education strategies that best prepare Alaskans to respond to the issue. I integrate an ecological field experiment, a citizen science program where data is used to validate phenology models derived from heraium data, and an invasive plants education experiment testing the effects of a metacognitive learning intervention to provide multiple perspectives that inform the management of invasive plants in Alaska. The ecological field experiment found that invasive Melilotus albus acts as a magnet species for pollinators, which increased seed production in Vaccinium vitis-idaea, slightly decreased pollination in Rhododendron groenlandicum, and had no detectable interactions with Vaccinium uliginosum. The impact M. albus had on R. groenlandicum changed with distance from the invasive plant patch, but the impact on V. vitis-idaea did not. Using data from a statewide citizen science program monitoring the phenology of these species, I found that herbarium-based phenology models were valid for assessing relative shifts in phenology of these species across Alaska. Employing the research on M. albus and the berry species as a test case, I found that students who received the metacognitive learning intervention show long-term improvement in metacognitive skills compared to students in the control group, but that the groups did not differ in their ability to apply resilience thinking skills to the environmental problem-solving. I synthesized social-ecological resilience and education research to investigate how citizen science and metacognitive learning could contribute to the capacity of Alaskans to respond to social-ecological change. Together, the ecology and education research presented here provide diverse perspectives on how to best manage and build the human capacity to manage M. albus near subsistence plant species.
    • Inversion of focal mechanism data for the directions of stress near Redoubt Volcano, Alaska

      Sánchez-Aguilar, John Jairo; McNutt, Stephen R.; Christensen, Douglas H.; Gardner, James E.; Moran, Seth C.; Wyss, Max (2000-12)
    • Investigating ancient bison migration in Alaska: a bottom up approach using isotopes

      Funck, Juliette Marie; Wooller, Matthew; Druckenmiller, Patrick; Hundertmark, Kris; Ruether, Joshua (2020-05)
      Once abundant in the Arctic, bison (Bison bison) declined almost to extinction in the North but have subsequently been reintroduced into Alaska. The predecessors of these modern bison were the ancient steppe bison (Bison priscus), which were abundant throughout the Northern Hemisphere before their extinction during the Holocene. This thesis investigates the ecology and landscape-use of both the present-day wood bison (Bison bison athabascae) and the ancient steppe bison in Alaska using stable isotopes, among other methods. The stable carbon and nitrogen isotope compositions of animal tissues are traditionally used to investigate diet. However, this thesis uses the isotope composition of tail hairs from present day wood bison as a proxy for their nutritional stress. Nutritional stress of some wood bison appears to be influenced not only by food shortage during hard seasons, but also due to long-distance mobility. This insight provides a key to understanding the challenges of reintroduction of the species into Alaska today, and can also be applied to understand the nutritional stress and cost of dispersal by ancient animals. Whereas the mobility of present-day bison can be tracked using sophisticated satellite tracking technologies, studies of the paleo-mobility of ancient bison rely on isotopic markers such as strontium and oxygen isotope ratios preserved in their teeth. To aid this approach using isotopic geolocation, this thesis creates a map of bioavailable strontium modeled and based on strontium isotope composition of present-day rodent teeth from across Alaska. It then compares this map, together with an existing oxygen isotope map of precipitation in Alaska, with the strontium and oxygen isotopes preserved in a suite of ancient bison from Northern Alaska. This comparison brings to light some of the major habitation regions used by Bison on the North Slope of Alaska over the last ~50,000 years. Finally, these findings subsequently contribute to a detailed paleoecological investigation of a mostly articulated and complete ancient steppe bison found on the North Slope of Alaska. This final study reveals the life-history of an individual bison that dispersed from the coastal plain to the foothills of the Brooks Range early in his life, and shows that the trip was nutritionally costly. This information is combined with a suite of other paleoecological methods to provide a vivid life history of this ancient bison. We introduce new methodologies for studying these ancient animals that seek to bridge the gap between how we study present-day and the past.
    • Investigating The Retention Of Bright And Dark Ejecta From Small Rayed Craters On Mars

      Calef, Fred J., Iii; Herrick, Robert R. (2010)
      Impact cratering is one of the principal geologic processes operating throughout the solar system. On Mars, small rayed impact craters (SRC) form continuously and randomly on the surface. Ejecta retention, the timespan and ability of excavated ejecta to remain in place around a crater rim, records a lineage of recent surface processes. However, the timescales under which small rayed craters are produced and their origin, whether terrestrial or cosmic, plays an important role in further investigating surface processes and possible recent climate variations. By examining thousands of randomly chosen panchromatic images from the Mars Orbiter Camera Narrow Angle (MOCNA) camera, a population of 630 SRC was catalogued across three equatorial and two polar regions on Mars. The survey of MOCNA images also revealed intriguing Enigmatic Linear Features (ELFs) in the northern hemisphere of Mars, which a short side study revealed to be a unique form of dust-devil track. From statistically examining several physical parameters, dust deposition and periglacial erosion were found to be the major factors affecting ejecta retention for the SRC. SRC morphology revealed ejecta retention sequences that followed four stages of ejecta retention from the initial impact to eventual erasure from the surface. By reconstructing the current cratering rate from estimates of atmospheric filtering, it was possible to calculate the ejecta retention age across Mars. In general, SRC ejecta are retained on the surface for <100 ka. Based on ejecta morphology and retention age estimates, a possible shift from depositional to erosional processes just south of the Martian equator is suspected to have occurred within this timeframe.
    • An investigation into the effectiveness of simulation-extrapolation for correcting measurement error-induced bias in multilevel models

      Custer, Christopher (2015-04)
      This paper is an investigation into correcting the bias introduced by measurement errors into multilevel models. The proposed method for this correction is simulation-extrapolation (SIMEX). The paper begins with a detailed discussion of measurement error and its effects on parameter estimation. We then describe the simulation-extrapolation method and how it corrects for the bias introduced by the measurement error. Multilevel models and their corresponding parameters are also defined before performing a simulation. The simulation involves estimating the multilevel model parameters using our true explanatory variables, the observed measurement error variables, and two different SIMEX techniques. The estimates obtained from our true explanatory values were used as a baseline for comparing the effectiveness of the SIMEX method for correcting bias. From these results, we were able to determine that the SIMEX was very effective in correcting the bias in estimates of the fixed effects parameters and often provided estimates that were not significantly different than those from the estimates derived using the true explanatory variables. The simulation also suggested that the SIMEX approach was effective in correcting bias for the random slope variance estimates, but not for the random intercept variance estimates. Using the simulation results as a guideline, we then applied the SIMEX approach to an orthodontics dataset to illustrate the application of SIMEX to real data.
    • Investigation of North Pacific sea ice anomalies in the context of atmospheric and oceanic variability

      Tivy, Adrienne (2001-08)
      This study investigates the main mode of variability in North Pacific sea ice and examines the relationship between sea ice concentration and northern hemispheric climate variability for the period 1968-1997. Through empirical orthogonal function (EOF) analysis, correlations, and composite analysis, it was found that the seesaw pattern (first EOF of wintertime sea ice concentrations) between ice concentrations in the Bering Sea and the Sea of Okhotsk, generally used to characterize North Pacific sea ice, does not adequately address variability in the Sea of Okhotsk. Relationships between the sea ice dipole and the large-scale circulation were investigated and were found to change with the 1977 and 1989 regime shifts in the North Pacific climate. Before 1977 the sea ice dipole is strongly related to tropical variability while after 1977 the dipole is more strongly related to mid-latitude variability.
    • Investigation of novel secondary metabolites of colophospermum mopane

      Englund, Brian Michael (2005-05)
      Labdanes are a large and important class of diterpenes. Colophospermum mopane seems to be a source of 'primitive' 9, 13-epoxylabdanes. The structures of these compounds are 'missing links' in the biogenesis of 9, 13-epoxylabdanes. This research reports a new compound extracted from the seeds of C. mopane. The structures of this compound has been completely elucidated by NMR spectroscopy, and the stereochemistry of the compound supports predictions based on biosynthetic arguments. Furthermore, this thesis also corrects NMR assignments previously reported by another group.
    • Investigation of strongly ducted infrasonic dispersion using a vertical eigenfunction expansion of the Helmholtz equation in a modal broad band acoustic propagation code

      Edon, Robert Alexander; Olson, John V.; Fee, David E.; Szuberla, Curt A. (2015-12)
      This study investigates an infrasound propagation model created by the National Center for Physical Acoustics (NCPA) which is applied to atmospheric data with a strong temperature inversion in the lower atmosphere. This temperature inversion is believed to be the primary cause of a dispersed infrasonic signal recorded by an infrasound sensor array located on the Southern California coast in August, 2012. The received signal is characterized by initial low frequency content followed by a high frequency content tail. It is shown the NCPA model is hindered by limited atmospheric data and no ground truth for the source function which generated the received signal. The results of the NCPA model are shown to not reproduce the recorded signal and provide inconclusive evidence for infrasonic dispersion.
    • Investigation Of The Allosteric Modulators Desformylflustrabromine And 4-(2-Hydroxyethyl)-1-Piperazineethanesulfonic Acid (Hepes) Interactions On Nicotinic Acetylcholine Receptors

      Daniello-Weltzen, Maegan M.; Schulte, Marvin K. (2011)
      Neuronal nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop super family of ligand gated ion channels. Dysregulation of nAChRs can lead to pathologies such as Alzheimer's disease, Parkinson's disease, Autism and nicotine addiction. Possible new therapeutic avenues are positive allosteric modulators (PAMs). The natural product desformylflustrabromine (dFBr), a tryptophan metabolite of the marine bryozoan Flustra foliacea, was found to be PAM of alpha4beta2 nAChR. Evaluation of our synthetic water soluble dFBr salt by two-electrode voltage clamp of Xenopus laevis oocytes expressing human nAChR confirmed that synthetic dFBr displayed similar properties as the natural product. Low concentrations of the synthetic dFBr enhanced ACh's efficacy on alpha4beta2 receptors. At higher dFBr concentrations, dFBr inhibited ACh potentiated responses. On alpha7 receptors, dFBr inhibited ACh induced currents. Further pharmacological characterization of dFBr revealed that dFBr was able to enhance partial agonist potencies and efficacies. Evaluation of dFBr on antagonists showed no effect on antagonist inhibition. The mechanisms of biphasic modulation (potentiation and inhibition) of dFBr on alpha4beta2 nAChR were also investigated. Enhanced efficacy of ACh induced currents by dFBr appeared to be accomplished by dFBr stabilization of the open receptor conformation by destabilization of the desensitized state. The inhibition of ACh potentiated currents by dFBr appeared to involve open-channel block. To better understand dFBr mechanisms, its putative binding site was examined. Alanine mutations were made in non-orthosteric clefts on the beta2+ and alpha4- faces. Results revealed residues located on these faces are involved in ACh induced conformational change of the receptor. In addition our data supports our hypothesis that allosteric modulation by dFBr interacts with residues located on the beta2+ and alpha4- faces. The new novel actions of (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) (HEPES) as a alpha4beta2 stoichiometric PAM was discovered and characterized. We showed that HEPES, a common buffering agent, potentiated the high ACh sensitivity alpha4beta2 receptor while only inhibiting the low ACh sensitivity alpha4beta2 receptor. Mutagenesis results suggested that residue beta2D217 is a critical residue in the HEPES binding site. Results from these studies will aid in the development of therapeutic ligands that will assist in the treatment of diseases where nAChRs are dysregulated.
    • Investigation of thin midlevel ice clouds in the Arctic using calipso data and radiative transfer modeling

      Kayetha, Vinay Kumar; Collins, Richard; Meyer, Franz; Prakash, Anupma; Bhatt, Uma (2015-08)
      In this research we investigate the global occurrence and properties of optically thin midlevel ice clouds. These clouds are difficult to detect with passive radiometric techniques and are under-represented in current studies. We use the Cloud Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) data set to identify thin midlevel ice clouds and determine their global occurrence and distribution. For the first time, we find that the global mean occurrence of these clouds is at least 4.5%, being at least 7.3% of all the tropospheric clouds detected at a horizontal scale of 10 km. Seasonally, these clouds are found most commonly in the polar regions. These clouds occur most commonly in the Arctic in winter and least commonly in the summer. In winter these clouds can occur up to 19% of the time. The occurrence of these clouds decreases with increasing spatial scale and are most commonly found at spatial scales of 25 km or less. We found five large distinct clouds over the Arctic and investigated them for their meteorological conditions and radiative effects. These thin midlevel ice clouds are formed along the frontal zones in weakly ascending air masses. Our model simulations show that thin midlevel ice clouds have a net warming effect on the surface of 23-48 W/m². We conclude that these clouds have a significant impact on the radiation budget in Arctic winters. Our study highlights the importance of active satellite-based remote sensing in globally detecting and characterizing optically thin clouds. Our estimates of occurrence and fraction of clouds represents a lower bound, as these clouds can be obscured by optically thicker clouds. The volume of measurements provided by the satellite allowed us to identify a small but consistent set of large clouds with which we could conduct a contemporary radiative analysis. These findings can be used to improve the representation of clouds and their impacts in regional and global climate models.