148 research outputs found
Measurements of High-Frequency Atmospheric Turbulence and Its Impact on the Boundary Layer of Wind Turbine Blades
To gain insight into the differences between onshore and offshore atmospheric turbulence,
pressure fluctuations were measured for offshore wind under different environmental conditions.
A durable piezo-electric sensor was used to sample turbulent pressure data at 50 kHz. Offshore
measurements were performed at a height of 100 m on Germany’s FINO3 offshore platform in the
German Bight together with additional meteorological data provided by Deutscher Wetterdienst
(DWD). The statistical evaluation revealed that the stability state in the atmospheric boundary does
not seem to depend on simple properties like the Reynolds number, wind speed, wind direction,
or turbulence level. Therefore, we used higher statistical properties (described by so-called shape
factors) to relate them to the stability state. Data was classified to be either within an unstable,
neutral, or stable stratification. We found that, in case of stable stratification, the shape factor was
mostly close to zero, indicating that a thermally stable environment produces closer-to Gaussian
distributions. Non-Gaussian distributions were found in unstable and neutral boundary layer states,
and an occurrence probability was estimated. Possible impacts on the laminar-turbulent transition on
the blade are discussed with the application of so-called laminar airfoils on wind turbine blades
K\u3csub\u3eV\u3c/sub\u3e4.2 channels tagged in the S1-S2 loop for alpha-bungarotoxin binding provide a new tool for studies of channel expression and localization
We report the first successful insertion of an engineered, high-affinity alpha-bungarotoxin (Bgtx) binding site into a voltage-gated ion channel, KV4.2, using a short, intra-protein embedded sequence (GGWRYYESSLEPYPDGG), derived from a previously described mimotope peptide, HAP. A major benefit to this approach is the ability to live-image the distribution and fate of functional channels on the plasma membrane surface. The Bgtx binding sequence was introduced into the putative extracellular loop between the S1 and S2 transmembrane domains of KV4.2. Following co-expression with KChIP3 in tsA201 cells, S1-S2 HAP-tagged channels express at levels comparable to wild-type KV4.2, and their activation and inactivation kinetics are minimally altered under most conditions. Binding assays, as well as live staining of surface-expressed KV4.2 channels with fluorescent-Bgtx, readily demonstrate specific binding of Bgtx to HAP-tagged KV4.2 expressed on the surface of tsA201 cells. Similar live-imaging results were obtained with HAP-tagged KV4.2 transfected into hippocampal neurons in primary culture suggesting applicability for future in vivo studies. Furthermore, the activation kinetics of S1-S2-tagged KV4.2 channels are minimally affected by the binding of Bgtx, suggesting a limited role if any for the S1-S2 loop in voltage sensing or gating associated conformational changes. Successful functional insertion of the HAP sequence into the S1-S2 linker of KV4.2 suggests that other related channels may similarly be amenable to this tagging strategy
Dynamic visualization of membrane-inserted fraction of pHluorin-tagged channels using repetitive acidification technique
<p>Abstract</p> <p>Background</p> <p>Changes in neuronal excitability, synaptic efficacy and generally in cell signaling often result from insertion of key molecules into plasma membrane (PM). Many of the techniques used for monitoring PM insertion lack either spatial or temporal resolution.</p> <p>Results</p> <p>We improved the imaging method based on time-lapse total internal reflection fluorescence (TIRF) microscopy and pHluorin tagging by supplementing it with a repetitive extracellular acidification protocol. We illustrate the applicability of this method by showing that brief activation of NMDA receptors ("chemical LTP") in cultured hippocampal neurons induced a persistent PM insertion of glutamate receptors containing the pHluorin-tagged GluR-A(flip) subunits.</p> <p>Conclusion</p> <p>The repetitive acidification technique provides a more accurate way of monitoring the PM-inserted fraction of fluorescently tagged molecules and offers a good temporal and spatial resolution.</p
Elevated tau and interleukin-6 concentrations in adults with obstructive sleep apnea
The article of record as published may be found at http://dx.doi.org/10.1016/j.sleep.2017.11.1121Obstructive sleep apnea (OSA) is characterized by apneas and hypopneas that result in hypoxia, cerebral hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress. These pathophysiologic processes likely contribute to neuronal damage. Tau is a protein that stabilizes microtubules and, along with amyloid beta (Ab), is associated with neurodegenerative processes. We sought to determine if tau and other biomarkers of inflammation were related to OSA severity. Concentrations of tau, Ab40, Ab42, c-reactive protein (CRP), TNF-a, interleukin (IL)-6, and IL-10 were measured in blood and compared between participants with moderate-severe OSA (n 1⁄4 28), those with mild OSA (n 1⁄4 22), and healthy controls (n 1⁄4 24). The cohort included relatively young, primarily male active duty military personnel without a history of traumatic brain injury or neurodegenerative disease. Total biomarker concentrations were determined from plasma samples using an ultra-sensitive detection method, SimoaTM, and CRP was assayed by ELISA. Total tau and IL-6 concentrations were elevated in participants with moderate-severe OSA, with a mean apnea-hypopnea index (AHI) of 26.1/h, compared to those with mild OSA (mean AHI 8.6/h) and healthy controls (mean AHI 2.1/h). Tau concentrations were also significantly correlated with the AHI (r 1⁄4 0.342, p 1⁄4 0.004). Our findings show that tau is elevated in the blood of young patients with moderate-severe OSA, suggesting that this degree of sleep-disordered breathing is a contributing factor in the development of neurodegenerative disorders. The finding of increased IL-6 further suggests that inflammatory biomarkers are present early in the course of this chronic disease
CSF and Plasma Amyloid-beta Temporal Profiles and Relationships with Neurological Status and Mortality after Severe Traumatic Brain Injury
The role of amyloid-β (Aβ) neuropathology and its significant changes in biofluids after traumatic brain injury (TBI) is still debated. We used ultrasensitive digital ELISA approach to assess amyloid-β1-42 (Aβ42) concentrations and time-course in cerebrospinal fluid (CSF) and in plasma of patients with severe TBI and investigated their relationship to injury characteristics, neurological status and clinical outcome. We found decreased CSF Aβ42 levels in TBI patients acutely after injury with lower levels in patients who died 6 months post-injury than in survivors. Conversely, plasma Aβ42 levels were significantly increased in TBI with lower levels in patients who survived. A trend analysis showed that both CSF and plasma Aβ42 levels strongly correlated with mortality. A positive correlation between changes in CSF Aβ42 concentrations and neurological status as assessed by Glasgow Coma Scale (GCS) was identified. Our results suggest that determination of Aβ42 may be valuable to obtain prognostic information in patients with severe TBI as well as in monitoring the response of the brain to injury
Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients.
Quantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously
Impact of Monetary Uncertainty and Economic Uncertainty on Money Demand in Africa
This dissertation investigates the role that economic uncertainties and monetary uncertainties play in the money demand function for 21 African countries. The Auto-regressive Distributive Lag (ARDL) and F-test approach are employed using quarterly time series data covering the period from 1971I-2012IV. In particular, this paper aims to demonstrate both short and long-run relationships between the dependent variables, Real Money Aggregate (M2), and the independent variables that include real income (Y), inflation rate nominal effective exchange rate (NEX), output uncertainty (VY), and monetary uncertainty (VM). We apply GARCH methodology to approximate the uncertainty measures. The empirical results show that except for Egypt, monetary VM and VY have significant short-run as well as long-run effects on money demand in all the countries, with some variables carrying negative or positive coefficient. We find that the coefficients of Y in all the countries is positive while that of and NEX are negative, implying depreciation of domestic currency decreases demand for money. The results also indicate that CUSUM and CUSUMSQ test are stable, thus M2 is stable in all the countries except Egyp
Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons
A molecular basis of survival from neuronal injury is essential for the development of therapeutic strategy to remedy neurodegenerative disorders. In this study, we demonstrate that an EF-hand Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1), one of the key proteins for various neuronal functions, also acts as an important survival factor. Overexpression of NCS-1 rendered cultured neurons more tolerant to cell death caused by several kinds of stressors, whereas the dominant-negative mutant (E120Q) accelerated it. In addition, NCS-1 proteins increased upon treatment with glial cell line–derived neurotrophic factor (GDNF) and mediated GDNF survival signal in an Akt (but not MAPK)-dependent manner. Furthermore, NCS-1 is significantly up-regulated in response to axotomy-induced injury in the dorsal motor nucleus of the vagus neurons of adult rats in vivo, and adenoviral overexpression of E120Q resulted in a significant loss of surviving neurons, suggesting that NCS-1 is involved in an antiapoptotic mechanism in adult motor neurons. We propose that NCS-1 is a novel survival-promoting factor up-regulated in injured neurons that mediates the GDNF survival signal via the phosphatidylinositol 3-kinase–Akt pathway
Contact-dependent aggregation of functional Ca 2+ channels, synaptic vesicles and postsynaptic receptors in active zones of a neuromuscular junction
Abstract To examine whether Ca 2+ channels aggregate in a contact-dependent manner, we characterized the distribution of synaptic vesicles and postsynaptic receptors, and compared it to the location of Ca 2+ entry sites, in a Xenopus laevis nerve-muscle coculture preparation using a localized Ca 2+ detection method. The majority (75%) of Ca 2+ entry sites at spontaneously formed nerve±muscle contacts were associated with enhanced immuno¯uorescence to the synaptic vesicle protein, SV2. In contrast, only 11% of recorded sites without Ca 2+ transients exhibited signi®cant SV2 immuno¯uorescence. When comparing the spatial distribution of synaptic markers with that of Ca 2+ entry sites, we found that the majority of Ca 2+ entry sites (61%) were associated with both enhanced SV2 immuno¯uorescence and R-BTX¯uorescence, thereby identifying putative neurotransmitter release sites where Ca 2+ channels, synaptic vesicles and postsynaptic receptors are colocalized. Using polystyrene beads coated with a heparin binding protein known to mediate in vitro postsynaptic receptor clustering, we show that the location of Ca 2+ domains was associated with enhanced SV2 immuno¯uorescence at neurite-to-bead contacts. We conclude that the localization of functional Ca 2+ channels to putative active zones follows a contact-dependent signalling mechanism similar to that known to mediate vesicle aggregation and AChR clustering
Evolution of Hierarchically Porous Nickel Alumina Catalysts Studied by X‐Ray Ptychography
The synthesis of hierarchically porous materials usually requires complex experimental procedures, often based around extensive trial and error approaches. One common synthesis strategy is the sol–gel method, although the relation between synthesis parameters, material structure and function has not been widely explored. Here, in situ 2D hard X‐ray ptychography (XRP) and 3D ptychographic X‐ray computed tomography (PXCT) are applied to monitor the development of hierarchical porosity in Ni/Al(2)O(3) and Al(2)O(3) catalysts with connected meso‐ and macropore networks. In situ XRP allows to follow textural changes of a dried gel Ni/Al(2)O(3) sample as a function of temperature during calcination, activation and CO(2) methanation reaction. Complementary PXCT studies on dried gel particles of Ni/Al(2)O(3) and Al(2)O(3) provide quantitative information on pore structure, size distribution, and shape with 3D spatial resolution approaching 50 nm, while identical particles are imaged ex situ before and after calcination. The X‐ray imaging results are correlated with N(2)‐sorption, Hg porosimetry and He pycnometry pore characterization. Hard X‐ray nanotomography is highlighted to derive fine structural details including tortuosity, branching nodes, and closed pores, which are relevant in understanding transport phenomena during chemical reactions. XRP and PXCT are enabling technologies to understand complex synthesis pathways of porous materials
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