1,144 research outputs found
Applying black hole perturbation theory to numerically generated spacetimes
Nonspherical perturbation theory has been necessary to understand the meaning
of radiation in spacetimes generated through fully nonlinear numerical
relativity. Recently, perturbation techniques have been found to be successful
for the time evolution of initial data found by nonlinear methods. Anticipating
that such an approach will prove useful in a variety of problems, we give here
both the practical steps, and a discussion of the underlying theory, for taking
numerically generated data on an initial hypersurface as initial value data and
extracting data that can be considered to be nonspherical perturbations.Comment: 14 pages, revtex3.0, 5 figure
Quantitative changes in intracellular calcium and extracellular-regulated kinase activation measured in parallel in CHO cells stably expressing serotonin (5-HT) 5-HT2A or 5-HT2C receptors
<p>Abstract</p> <p>Background</p> <p>The serotonin (5-HT) 2A and 2C receptors (5-HT<sub>2A</sub>R and 5-HT<sub>2C</sub>R) are involved in a wide range of physiological and behavioral processes in the mammalian central and peripheral nervous systems. These receptors share a high degree of homology, have overlapping pharmacological profiles, and utilize many of the same and richly diverse second messenger signaling systems. We have developed quantitative assays for cells stably expressing these two receptors involving minimal cell sample manipulations that dramatically improve parallel assessments of two signaling responses: intracellular calcium (<it>Ca<sub>i</sub></it><sup>++</sup>) changes and activation (phosphorylation) of downstream kinases. Such profiles are needed to begin to understand the simultaneous contributions from the multiplicity of signaling cascades likely to be initiated by serotonergic ligands.</p> <p>Results</p> <p>We optimized the <it>Ca<sub>i</sub></it><sup>++ </sup>assay for stable cell lines expressing either 5-HT<sub>2A</sub>R or 5-HT<sub>2C</sub>R (including dye use and measurement parameters; cell density and serum requirements). We adapted a quantitative 96-well plate immunoassay for pERK in the same cell lines. Similar cell density optima and time courses were observed for 5-HT<sub>2A</sub>R- and 5-HT<sub>2C</sub>R-expressing cells in generating both types of signaling. Both cell lines also require serum-free preincubation for maximal agonist responses in the pERK assay. However, 5-HT<sub>2A</sub>R-expressing cells showed significant release of <it>Ca<sub>i</sub></it><sup>++ </sup>in response to 5-HT stimulation even when preincubated in serum-replete medium, while the response was completely eliminated by serum in 5-HT<sub>2C</sub>R-expressing cells. Response to another serotonergic ligand (DOI) was eliminated by serum-replete preincubation in both cells lines.</p> <p>Conclusions</p> <p>These data expand our knowledge of differences in ligand-stimulated signaling cascades between 5-HT<sub>2A</sub>R and 5-HT<sub>2C</sub>R. Our parallel assays can be applied to other cell and receptor systems for monitoring and dissecting concurrent signaling responses.</p
Anatomy Nights: An international public engagement event increases audience knowledge of brain anatomy
Anatomy Nights is an international public engagement event created to bring anatomy and anatomists back to public spaces with the goal of increasing the public's understanding of their own anatomy by comparison with non-human tissues. The event consists of a 30-minute mini-lecture on the anatomy of a specific anatomical organ followed by a dissection of animal tissues to demonstrate the same organ anatomy. Before and after the lecture and dissection, participants complete research surveys designed to assess prior knowledge and knowledge gained as a result of participation in the event, respectively. This study reports the results of Anatomy Nights brain events held at four different venues in the UK and USA in 2018 and 2019. Two general questions were asked of the data: 1) Do participant postevent test scores differ from pre-event scores; and 2) Are there differences in participant scores based on location, educational background, and career. We addressed these questions using a combination of generalized linear models (R's glm function; R version 4.1.0 [R Core Team, 2014]) that assumed a binomial distribution and implemented a logit link function, as well as likelihood estimates to compare models. Survey data from 91 participants indicate that scores improve on post-event tests compared to pre-event tests, and these results hold irrespective of location, educational background, and career. In the pre-event tests, participants performed well on naming structures with an English name (frontal lobe and brainstem), and showed signs of improvement on other anatomical names in the posttest. Despite this improvement in knowledge, we found no evidence that participation in Anatomy Nights improved participants' ability to apply this knowledge to neuroanatomical contexts (e.g., stroke)
A computationally engineered RAS rheostat reveals RAS-ERK signaling dynamics.
Synthetic protein switches controlled with user-defined inputs are powerful tools for studying and controlling dynamic cellular processes. To date, these approaches have relied primarily on intermolecular regulation. Here we report a computationally guided framework for engineering intramolecular regulation of protein function. We utilize this framework to develop chemically inducible activator of RAS (CIAR), a single-component RAS rheostat that directly activates endogenous RAS in response to a small molecule. Using CIAR, we show that direct RAS activation elicits markedly different RAS-ERK signaling dynamics from growth factor stimulation, and that these dynamics differ among cell types. We also found that the clinically approved RAF inhibitor vemurafenib potently primes cells to respond to direct wild-type RAS activation. These results demonstrate the utility of CIAR for quantitatively interrogating RAS signaling. Finally, we demonstrate the general utility of our approach in design of intramolecularly regulated protein tools by applying it to the Rho family of guanine nucleotide exchange factors
Demonstration of a switchable damping system to allow low-noise operation of high-Q low-mass suspension systems
Low mass suspension systems with high-Q pendulum stages are used to enable
quantum radiation pressure noise limited experiments. Utilising multiple
pendulum stages with vertical blade springs and materials with high quality
factors provides attenuation of seismic and thermal noise, however damping of
these high-Q pendulum systems in multiple degrees of freedom is essential for
practical implementation. Viscous damping such as eddy-current damping can be
employed but introduces displacement noise from force noise due to thermal
fluctuations in the damping system. In this paper we demonstrate a passive
damping system with adjustable damping strength as a solution for this problem
that can be used for low mass suspension systems without adding additional
displacement noise in science mode. We show a reduction of the damping factor
by a factor of 8 on a test suspension and provide a general optimisation for
this system.Comment: 5 pages, 5 figure
New Technique to Improve the Ductility of Steel Beam to Column Bolted Connections: A Numerical Investigation
From MDPI via Jisc Publications RouterHistory: accepted 2021-10-12, pub-electronic 2021-10-22Publication status: PublishedA novel method to improve the robustness of steel end plate connections is presented in this paper. Existing commonly adopted techniques alter the stiffness of the beam or the end plate to improve the connectionās robustness. In this study, the robustness is enhanced by improving the contribution of the bolts to the rotational capacity of connections; the higher the boltsā elongation, the higher the rotational capacity that can be achieved. However, the brittleness of the bolt material, combined with its small length, results in negligible elongation. Alternatively, the load path between the end plate and the bolts can be interrupted with a ductile element to achieve the required elongation. This can be achieved by inserting a steel sleeve with a designated length, thickness, and wall curvature between the end plate and the washer. The proposed sleeve should be designed so that its ultimate capacity is less than the force in the bolt at failure; accordingly, the sleeve develops a severe bending deformation before the failure of any connection components. Using a validated finite element model, end plate connections with various parameters are numerically investigated to understand the performance of the sleeve device. The proposed system substantially enhances the rotational capacity of the connections, ranging between 1.37 and 2.46 times that of the standard connection. It is also concluded that the sleeved connections exhibit a consistent elastic response with the standard connections, indicating the proposed system is compatible with codified elastic design approaches without modification. Furthermore, for a specific connection, various ductile responses can be achieved without altering the connection capacity nor configuration
Demodicosis in a captive African straw-coloured fruit bat (Eidolon helvum).
Demodicosis is most frequently observed in the domestic dog (Canis familiaris), but it has rarely been reported in bats (Chiroptera). The overpopulation of Demodex spp. that causes dermatological changes is generally associated with a compromised immune system. We describe the gross and histological features of generalized demodicosis in an adult female African straw-coloured fruit bat (Eidolon helvum) drawn from a captive research colony. The histology of the lesions revealed comedones and follicular infundubular cysts harbouring numerous Demodex spp. mites, eliciting a minimal inflammatory response in the adjacent dermis. The histological examination of a full set of tissues did not reveal clear evidence of immunosuppression, although a clinical history of recent abortion and possible stressors due to captivity could be considered risk factors for the demodicosis. Attempts to determine the Demodex species using PCR on DNA extracted from the formalin fixed paraffin embedded tissue failed. This is the first clinical and histological description of demodicosis in Eidolon helvum
High-precision natural dose rate estimates through beta counting
The beta-particle emission from a sediment or rock sample can be measured very precisely using beta-counting instruments. The observed count rate is largely a function of the radionuclide concentration in the sample, so has the potential to provide a precise estimate of the natural radiation dose rate. However, the count rate is also sensitive to the attenuation of beta particles in the sample, and the relative proportions of the different radionuclide sources. Here we devise a correction for the self-attenuation effect using dilution analysis, and show that imprecise prior knowledge of radionuclide activity is sufficient for calculation of an accurate combined beta-plus-gamma dry dose rate. The method is tested on a selection of archive samples, and compared with results from high-resolution gamma-spectrometry. We show that with counting uncertainty ā¼2%, and calibration uncertainty ā¼2%, the total random uncertainty of the beta-plus-gamma dry dose rate is less than 3%. For most natural sediments, this level of precision equal to, or better than, that obtainable with other methods
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