390 research outputs found
Communicating stroke: a narrative inquiry
Thesis (M.A.) University of Alaska Fairbanks, 2008This narrative research in communication addresses the lived experience of individuals who have suffered stroke. Specifically, I examine how the realities people create and the relationships they enact contribute to their sense of identity after the occurrence of a stroke. Health crises are times of reconstitution of self and relationships (Lorber, 1997). The present research has been conducted from a human science perspective, employing the epistemology of constructionism, the theory of social construction of reality, and narrative inquiry and conversational interviewing to produce an understanding of the experience of life after stroke. In this study, stroke survivors are considered active interpreters, managers, and creators of the meaning of their health and illness.1. Review of related literature -- 1.1. Statement of the problem and goals of the research -- 1.2. Research on stroke rehabilitation -- 1.3. Social construction of illness : what does recovery mean? -- 1.4. Social construction of identity -- 1.5. The role of social support -- 2. Research methodologies -- 2.1. Research contexture -- 2.1.1.Ontology and epistemology -- 2.1.2. Theoretical perspective -- 2.1.3. Research methodology -- 2.1.4. Method : conversational interviewing -- 2.1.5. Method : thematic analysis -- 2.2. Participants -- 2.3. Procedure -- 2.4. Researcher as research tool -- 3. Narrative perspectives -- 3.1. Prudence's conversational interview -- 3.2. Julia's conversational interview -- 3.3. Michelle's conversational interview -- 3.4. Eleanor's conversational interview -- 3.5. Lucy's conversational interview -- 4. Human science research analysis -- 4.1. Theme one : I'm a survivor -- 4.2. Theme two : talk to me normal! -- 4.3. Theme three : I am a better person now -- 4.4. Theme four : I need support -- 4.5. Conclusion and prospects for further inquiry -- References -- Appendix
Modeling the carbon isotope signatures of methane and dissolved inorganic carbon to unravel mineralization pathways in boreal lake sediments
Vertical profiles of the concentration and isotopic composition (δ13C) of methane (CH4) and dissolved inorganic carbon (DIC), as well as of ancillary parameters, were obtained in the top 25 cm sediment column of a seasonally anoxic basin from an oligotrophic boreal lake. Modeling the profiles of CH4 and DIC concentrations and those of their δ13C signatures with reaction-transport equations allowed us to determine the organic matter (OM) degradation rates according to various reactions and to constrain the in situ isotopic fractionation factors and diffusivity coefficients of CH4 and DIC. This exercise reveals inter alia that (i) CH4 production occurs below 5 cm depth, with the highest production rate between 5 and 7.5 cm depth, (ii) all CH4 is produced through hydrogenotrophy, and (iii) methanogenesis yields a production rate of CH4 about three times greater than that of DIC. This latter observation indicates either that fermentation of OM is not the exclusive source of H2 sustaining hydrogenotrophy, or that the commonly assumed model molecule CH2O does not adequately represent the fermenting OM, since its fermentation yields identical rates of CH4 and DIC production. The porewater profiles of Fe and View the MathML source suggest that some H2 may be produced during the reoxidation of reduced sulfur by Fe(III), but the rate of H2 production via this process, if active, would be insignificant in comparison to that required to sustain the estimated rate of hydrogenotrophy. We deduce that the imbalance between CH4 and DIC production rates is rather due to the fermentation of organic substrates that are more reduced than CH2O, i.e., having a negative average carbon oxidation state (COS). From the constraints on reaction rates and on fermentation pathways imposed by the δ13C data, we infer that the organic substrate fermenting between 5 and 7.5 cm depth should have a COS of −1.87. We thus submit that CH4 is produced in the sediments of the seasonally anoxic basin of our boreal lake through hydrogenotrophy coupled to the fermentation of reduced organic substrates that can be represented by a mixture of fatty acids (e.g. C16H32O2; COS of −1.75) and fatty alcohols (e.g., C16H34O; COS of −2.00). This study emphasizes the importance of characterizing the sedimentary OM undergoing mineralization in order to improve diagenetic model predictions of CH4 cycling in boreal lakes and of its significance in climate change
Flight Operations of Two Rapidly Assembled CubeSats with Commercial Infrared Cameras: The Rogue-Alpha,Beta Program
The Aerospace Corporation’s Rogue-alpha, betaprogram, co-funded by the Space and Missile Systems Center’s Development Corps, is a rapid prototyping effort that built and launched two 3-Unit CubeSats equipped with modified commercial IR camera payloads, laser communications and precision pointing capabilities in 18-months. Launched on 2 November 2019, the two spacecraft were released from the ISS Cygnus NG-12 robotic resupply spacecraft on 31 January 2020 into a circular 460-km, 52° inclined orbit. The two Rogue spacecraft are serving as testbeds for studying wide-field-of-view fast-framing imaging, on-orbit stellar calibration techniques for small IR payloads, and associated spacecraft flight operations. Precision pointing is enabled by three star sensors. High data rate sensor observations are enabled by the ultra-compact 200 Mbps lasercom system, which downlinks gigabytes of stored data during a single laser contact, using The Aerospace Corporation’s prototype ground stations located in El Segundo, California. The Rogue-alpha, beta IR sensor is a 1.4 micron band, 640x512 pixel, 28° field of view, InGaAs SWIR camera. It is accompanied by a panchromatic, 10-megapixel, 37° field of view visible context camera. Modes of sensor operation have included: 1) horizon-pointed imaging in all directions relative to the spacecraft orbit (fore, aft, port, and starboard) which is designed to maximize the imaged field of view, 2) point-and-stare imaging, 3) nadir-pointed, and 4) stereo fore-aft pointing using both spacecraft. All of these modes of operation are usually conducted in multi-frame collections at 1-20hz for dozens to thousands of frames. Highlights from the Rogue-alpha, beta sensor Earth remote sensing observation experiments will be presented. These have included impressive video imagery of hurricanes, typhoons, thunderstorms, and high clouds in the intra-tropical convergence zone. Infrared and visible point sources studied include gas flares, wildfires, active volcanos, nighttime lights, and other phenomena, including the first infrared CubeSat observations of space launch upper stages in flight. Stereo cloud imaging observations were also conducted with an aim of better understanding Earth backgrounds from low Earth orbit. Highlights from the CubeSat flight operations experiments include: 1) spacecraft-to-spacecraft boresight alignment of Rogue’s lasercom systems, and 2) metric and radiometric calibration of Rogue’s flight cameras using bright infrared stars. The results from the Rogue-alpha, beta460-km orbit show the exciting possibilities for wide-field-of-view missions from low earth orbit
Efgartigimod improved health-related quality of life in generalized myasthenia gravis: results from a randomized, double-blind, placebo-controlled, phase 3 study (ADAPT)
There are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled. HRQoL measures such as the Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) and EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) are vital for evaluating the clinical benefit of therapeutic interventions in patients with MG, as they assess the burden of disease and the effectiveness of treatment, as perceived by patients. The phase 3 ADAPT study (NCT03669588) demonstrated that efgartigimod-a novel neonatal Fc receptor inhibitor-was well tolerated and that acetylcholine receptor antibody-positive (AChR-Ab+) participants who received efgartigimod had statistically significant improvements in MG-specific clinical scale scores. The ancillary data reported here, which cover an additional treatment cycle, show that these participants had similar significant improvements in HRQoL measures, the MG-QOL15r and EQ-5D-5L utility and visual analog scales, and that these improvements were maintained in the second treatment cycle. Positive effects on HRQoL were rapid, seen as early as the first week of treatment in both treatment cycles, and maintained for up to 4 weeks in the follow-up-only portion of treatment cycles. The pattern of improvements in HRQoL paralleled changes in immunoglobulin G level, and correlational analyses show that improvements were consistent across HRQoL measures and with clinical efficacy measures in the ADAPT study. The substantial and durable improvements in HRQoL end points in this study demonstrate the broader benefit of treatment with efgartigimod beyond relief of immediate signs and symptoms of gMG.Neurological Motor Disorder
Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy.
Gain-of-function (GOF) variants in K+ channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+ currents lead to network hyperexcitability. Here, we introduce a human Na+-activated K+ (KNa) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, find motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increases KNa currents in cortical excitatory and inhibitory neurons, there is an increase in the KNa current across subthreshold voltages only in inhibitory neurons, particularly in those with non-fast-spiking properties, resulting in inhibitory-neuron-specific impairments in excitability and action potential (AP) generation. We further observe evidence of synaptic rewiring, including increases in homotypic synaptic connectivity, accompanied by network hyperexcitability and hypersynchronicity. These findings support inhibitory-neuron-specific mechanisms in mediating the epileptogenic effects of KCNT1 channel GOF, offering cell-type-specific currents and effects as promising targets for therapeutic intervention
Transgenic tomatoes expressing human beta-amyloid for use as a vaccine against Alzheimer’s disease
Human β-amyloid (Aβ) is believed to be one of the main components of Alzheimer’s disease, so reduction of Aβ is considered a key therapeutic target. Using Agrobacterium-mediated nuclear transformation, we generated transgenic tomatoes for Aβ with tandem repeats. Integration of the human Aβ gene into the tomato genome and its transcription were detected by PCR and Northern blot, respectively. Expression of the Aβ protein was confirmed by western blot and ELISA, and then the transgenic tomato line expressing the highest protein level was selected for vaccination. Mice immunized orally with total soluble extracts from the transgenic tomato plants elicited an immune response after receiving a booster. The results indicate that tomato plants may provide a useful system for the production of human Aβ antigen
Improved Mitochondrial Function with Diet-Induced Increase in Either Docosahexaenoic Acid or Arachidonic Acid in Membrane Phospholipids
Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP). We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6). Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs
Decadal-scale litter manipulation alters the biochemical and physical character of tropical forest soil carbon
© 2018 Elsevier Ltd Climate change and rising atmospheric carbon dioxide (CO2) concentrations are likely to alter tropical forest net primary productivity (NPP), potentially affecting soil C storage. We examined biochemical and physical changes in soil C fractions in a humid tropical forest where experimental litter manipulation changed total soil C stocks. We hypothesized that: (1.) low-density soil organic C (SOC) fractions are more responsive to altered litter inputs than mineral-associated SOC, because they cycle relatively rapidly. (2.) Any accumulation of mineral-associated SOC with litter addition is relatively stable (i.e. low leaching potential). (3.) Certain biomolecules, such as waxes (alkyl) and proteins (N-alkyl), form more stable mineral-associations than other biomolecules in strongly weathered soils. A decade of litter addition and removal affected bulk soil C content in the upper 5 cm by +32% and −31%, respectively. Most notably, C concentration in the mineral-associated SOC fraction was greater in litter addition plots relative to controls by 18% and 28% in the dry and wet seasons, respectively, accounting for the majority of greater bulk soil C stock. Radiocarbon and leaching analyses demonstrated that the greater mineral-associated SOC in litter addition plots consisted of new and relatively stable C, with only 3% of mineral-associated SOC leachable in salt solution. Solid-state13C NMR spectroscopy indicated that waxes (alkyl C) and microbial biomass compounds (O-alkyl and N-alkyl C) in mineral-associated SOC are relatively stable, whereas plant-derived compounds (aromatic and phenolic C) are lost from mineral associations on decadal timescales. We conclude that changes in tropical forest NPP will alter the quantity, biochemistry, and stability of C stored in strongly weathered tropical soils
Validation of Reference Genes for the Relative Quantification of Gene Expression in Human Epicardial Adipose Tissue
BACKGROUND: Relative quantification is a commonly used method for assessing gene expression, however its accuracy and reliability is dependent upon the choice of an optimal endogenous control gene, and such choice cannot be made a priori. There is limited information available on suitable reference genes to be used for studies involving human epicardial adipose tissue. The objective of the current study was to evaluate and identify optimal reference genes for use in the relative quantification of gene expression in human epicardial fat depots of lean, overweight and obese subjects. METHODOLOGY/PRINCIPAL FINDINGS: Some of the commonly used reference genes including 18S, ACTB, RPL27, HPRT, CYCA, GAPDH, RPLPO, POLR2A and B2M were quantified using real-time PCR analysis. The expression stability of these genes was evaluated using Genorm, Normfinder and Bestkeeper algorithms. In addition, the effect of sample size on the validation process was studied by randomly categorizing subjects in two cohorts of n = 2 and n = 33. CONCLUSIONS/SIGNIFICANCE: CYCA, GAPDH and RPL27 were identified as the most stable genes common to all three algorithms and both sample sizes. Their use as reference gene pairs might contribute to the enhanced robustness of relative quantification in the studies involving the human epicardial adipose tissue
Social modulation of androgen levels in male teleost fish
Androgens are classically thought of as the sex steroids controlling male reproduction. However, in recent years evidence has accumulated showing that androgens can also be affected by the interactions between conspecifics, suggesting reciprocal interactions between androgens and behaviour. These results have been interpreted as an adaptation for individuals to adjust their agonistic motivation and to cope with changes in their social environment. Thus, male–male interactions would stimulate the production of androgens, and the levels of androgens would be a function of the stability of its social environment [‘challenge hypothesis’, Gen. Comp. Endocrinol. 56 (1984) 417]. Here the available data on social modulation of androgen levels in male teleosts are reviewed and some predictions of the challenge hypothesis are addressed using teleosts as a study model. We investigate the causal link between social status, territoriality and elevated androgen levels and the available evidence suggests that the social environment indeed modulates the endocrine axis of teleosts. The association between higher androgen levels and social rank emerges mainly in periods of social instability. As reported in the avian literature, in teleosts the trade-off between androgens and parental care is indicated by the fact that during the parental phase breeding males decreased their androgen levels. A comparison of androgen responsiveness between teleost species with different mating and parenting systems also reveals that parenting explains the variation observed in androgen responsiveness to a higher degree than the mating strategy. Finally, the adaptive value of social modulation of androgens and some of its evolutionary consequences are discussed
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