Breaking through an actin cloud.
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Actins↗
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Implementing a training resource for large-scale genomic data analysis in the All of Us Researcher Workbench.
A lack of representation in genomic research and limited access to computational training create barriers for many researchers seeking to analyze large-scale genetic datasets. The All of Us Research Program provides an unprecedented opportunity to address these gaps by offering genomic data from a broad range of participants, but its impact depends on equipping researchers with the necessary skills to use it effectively. The All of Us Biomedical Researcher (BR) Scholars Program at Baylor College of Medicine aims to break down these barriers by providing early-career researchers with hands-on training in computational genomics through the All of Us Evenings with Genetics Research Program. The year-long program begins with the faculty summit, an in-person computational boot camp that introduces scholars to foundational skills for using the All of Us dataset via a cloud-based research environment. The genomics tutorials focus on genome-wide association studies (GWASs), utilizing Jupyter Notebooks and the Hail computing framework to provide an accessible and scalable approach to large-scale data analysis. Scholars engage in hands-on exercises covering data preparation, quality control, association testing, and result interpretation. By the end of the summit, participants will have successfully conducted a GWAS, visualized key findings, and gained confidence in computational resource management. This initiative expands access to genomic research by equipping early-career researchers from a variety of backgrounds with the tools and knowledge to analyze All of Us data. By lowering barriers to entry and promoting the study of representative populations, the program fosters innovation in precision medicine and advances equity in genomic research.
Humans↗
The collision of Jupiter and Comet Shoemaker-Levy 9.
A simple description of the disruption and deceleration of 100-m- to 5-km-diameter comets striking Jupiter is combined with numerical simulations of the subsequent explosions to predict the fate of Comet Shoemaker-Levy 9. Kilometer-size objects of density 1 g/cm3 explode at about the 10-bar level; a fragment of the same diameter but of density 0.3 g/cm3 explodes at about the 2-bar level. Detailed numerical simulations of the first 3 min of the explosion were performed using the astrophysical hydrodynamics program ZEUS-3D. Our numerical simulations begin either with hot cylinders with dimensions suggested by the disruption and deceleration model or with an initial wake constructed from a moving line charge. In all cases, extensive plumes of hot gas are expelled from the atmosphere. The models with wakes evolve about twice as fast as the initially confined models. Models of both types generate similar pressure waves into the planet. Temperatures and negative hydrogen ion opacities were computed by solving a battery of Saha equations. For atmospheric entry, light curves were computed assuming thermal radiation by clean jovian air with a surface area consistent with the (changing) cross-sectional area of the impactor. On entry the largest bolides could be very bright, possibly as bright as Jupiter for observers placed to see them, although for kilometer-size impactors the luminosity peak is obscured by clouds. The timescale is about 10 sec. For the fireball, light curves were computed from the numerical simulations assuming a grey atmosphere. Metals from the vaporized comet provide electrons that dramatically increase the opacity of Jovian air at low temperature; the resulting effective radiating temperature of the fireball is of order 3000 K. The fireball rises through and above the atmosphere, brightening at first as its surface area increases, but later fading to invisibility as its temperature drops and its opacity plummets. The timescale is about 100 sec.
Astronomy↗
Acute disseminated encephalitis documented by magnetic resonance imaging and computed tomography. Report of a case.
A 16-year-old girl developed left hemispheric deficits, which were followed by clouding of consciousness, quadriplegia, and subcortical blindness. Although we could not demonstrate a recent viral infection, the clinical features, laboratory and radiologic findings strongly suggested the diagnosis acute disseminated encephalitis. Cerebrospinal fluid abnormalities incompletely correlated with the clinical course. In contrast, X-ray computed tomography and particularly magnetic resonance imaging of the head closely reflected disease and improvement.
Acute Disease↗
Family-based tests of association in the presence of linkage.
Linkage analysis may not provide the necessary resolution for identification of the genes underlying phenotypic variation. This is especially true for gene-mapping studies that focus on complex diseases that do not exhibit Mendelian inheritance patterns. One positional genomic strategy involves application of association methodology to areas of identified linkage. Detection of association in the presence of linkage localizes the gene(s) of interest to more-refined regions in the genome than is possible through linkage analysis alone. This strategy introduces a statistical complexity when family-based association tests are used: the marker genotypes among siblings are correlated in linked regions. Ignoring this correlation will compromise the size of the statistical hypothesis test, thus clouding the interpretation of test results. We present a method for computing the expectation of a wide range of association test statistics under the null hypothesis that there is linkage but no association. To standardize the test statistic, an empirical variance-covariance estimator that is robust to the sibling marker-genotype correlation is used. This method is widely applicable: any type of phenotypic measure or family configuration can be used. For example, we analyze a deletion in the A2M gene at the 5' splice site of "exon II" of the bait region in Alzheimer disease (AD) discordant sibships. Since the A2M gene lies in a chromosomal region (chromosome 12p) that consistently has been linked to AD, association tests should be conducted under the null hypothesis that there is linkage but no association.
Algorithms↗
Equilibrium phase behavior of polydisperse hard spheres.
We calculate the phase behavior of hard spheres with size polydispersity, using accurate free energies for the fluid and solid phases. Cloud and shadow curves are found exactly by the moment free energy method, but we also compute the complete phase diagram, taking full account of fractionation. In contrast to earlier, simplified treatments we find no point of equal concentration between fluid and solid or reentrant melting at higher densities. Rather, the fluid cloud curve continues to the largest polydispersity that we study (14%); from the equilibrium phase behavior a terminal polydispersity can thus be defined only for the solid, where we find it to be around 7%. At sufficiently large polydispersity, fractionation into several solid phases can occur, consistent with previous approximate calculations; we find, in addition, that coexistence of several solids with a fluid phase is also possible.
Journal Article↗
[Personal computer interactive algorithm for estimating radiologic contamination and doses after a nuclear accident in Europe].
The algorithm RANA (radiological assessment of nuclear accidents) is a tool which can be exploited to estimate the space and time structure of the radiological consequences of a radioactive release following a nuclear accident in Europe. The algorithm, formulated in the language of Mathematica, can be run on a personal computer. It uses simplified physical assumptions as for the the diffusion of the cloud and the transfer of the contamination to the food chain. The user gets the needed information by means of interactive windows that allow a fast evaluation of dose and contamination profiles. Calculations are performed either starting from the source terms or from the knowledge of experimental contamination data. Radiological consequences, such as individual or collective doses from several exposure paths, are parametrized in terms of the atmospheric diffusion categories.
Air Pollution, Radioactive↗
Light tunneling in clouds.
Solar radiation, traveling outside cloud water droplets, excites sharp resonances and surface waves by tunneling into the droplets. This effect contributes substantially to the total absorption (typically, of the order of 20%) and yields the major contribution to backscattering, producing the meteorological glory. Usual computational practices in atmospheric science misrepresent resonance contributions and cannot be relied on in the assessment of possible anomalies in cloud absorption.
Journal Article↗
Probability calculus for quantitative HREM. Part I: Monte-Carlo and point cloud techniques.
A new approach to a central question of modern high-resolution electron microscopy (1-IREM) is presented: How precisely can we locate atom positions in crystal defects using computer-controlled structure retrieval algorithms? The purpose is not just to give error bars for the determined atomic column positions, but to derive estimations for the continuous probability functions. In the first part of this two-part paper, we present techniques which analyse point clouds of fluctuating fit-results for atom coordinates. The point clouds are obtained in a first approach from multiple input images differing in noise, commonly known as Monte-Carlo error estimation. Furthermore, we exploit the response obtained during a global optimisation-based refinement process for which all the trial structures are evaluated resulting in a second type of point cloud. In comparison, the Monte-Carlo-type technique turns out to be the most robust one. Using examples from current research on SrTiO3-bicrystals and Cu-Al2O3 interfaces, we study two largely different crystallographic and statistical situations.
Journal Article↗
A laboratory model for interstellar chemical evolution.
The chemistry in a supersonic plasma source flow was studied as a laboratory model for interstellar chemical evolution. It is important to match the similarity parameters for cosmic and laboratory conditions, which connect the temporal and spatial scales of the two cases. The apparatus simulated the conditions in a molecular cloud with respect to molecular-ionic reaction fraction, temperature, and non-equilibrium kinetics. The plasma flow was found to be cold enough, by the radical expansion, to produce polyatomic molecules. From the simple atomic plasma as reactant, cyanopolyyne and unsaturated hydrocarbons were synthesized in the present experiment. These molecules are also inherent in molecular clouds. The reaction mechanism is discussed.
Computer Simulation↗
High bubble concentrations produced by ultrasounds in binary mixtures.
It was discovered that simultaneous insonification and air blowing of different aqueous binary solutions such as water/sodium-dodecyl-sulphate (SDS), water/methanol or water/potassium-sulphate yields a very concentrated bubble cloud invading the whole vessel in a few seconds. After the end of insonification, this cloudiness remained in the solution for about 1 min. The phenomenon was investigated by computer-treatment of solution pictures recorded every second after the end of insonification. Turbidity appeared to increase with ultrasound power, and also with SDS concentration. During the disappearance of the cloud, a turbidity front appeared rising and spreading upward. This front was studied in the characteristic plane and interpreted as a spatial segregation of different bubble sizes rising with different terminal velocities. The bubble sizes involved were estimated to about 10 microns. Adsorption of surface active species are invoked to explain the cloud formation and its abnormally slow disappearance, but the occurrence of the phenomenon for potassium-sulphate salt remains unexplained.
Journal Article↗
Assessment of gamma-exposure due to a radioactive cloud released from a point source.
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Air Pollution, Radioactive↗
Image analysis of the lens opacities induced in developing chick embryo by glucocorticoid.
Glucocorticoid-induced cataracts in chick embryos were monitored by an image analysis system. Opacities in the lens visually showed a complex pattern with significant changes in the cortical and nuclear regions. An electronic image analyser produced an image in which contrast represented different zones of lens opacification in the frontal plane and documented objective lens findings such as the precise topography of the opacities, density and opacity measurements, geometric measurements of boundary surfaces and of regional areas. Parameters of lens clouding were evaluated quantitatively by measuring the optical density index and the area of the zones of clouding outlined with equi-densities. The light intensity standard graded different morphological areas of the lens into up to 256 grey levels. The data were entered and stored quantitatively into a computer. The lens images thus picked up by the TV camera and digitally stored in a frame buffer of the measuring system could be reliably transformed into a 2-D or 3-D picture of lens clouding. The approach demonstrated by the current study provides a sensitive and meaningful measure of cataractous changes for lens laboratory research.
Animals↗
[Unusual course of candidiasis of the central nervous system].
Six months after an attack of pyelonephritis, adnexitis and candida colpitis an 18-year-old girl developed some clouding of consciousness. On neurological examination she showed organic behavioural changes, discrete anisocoria and possible meningism. Computed tomography revealed hydrocephalus and signs of increased cerebrospinal fluid (CSF) pressure. CSF contained 2336/3 cells, while total protein was raised to 7.0 g/l and lactate concentration to 6.85 mmol/l. Glucose concentration in CSF was 51 mg/dl and 75 mg/dl in serum. As tuberculous meningitis was suspected, treatment was started with four tuberculostatic drugs, but there was no improvement. Five weeks later microscopic CSF examination showed fungal spores and nonbranching hyphae. The maximal candida haemagglutination titre in CSF was 1:2048. CSF culture grew Candida albicans. The further course was complicated by side effects to the antimycotic drugs (amphotericin B between 4.5 and 45 mg daily; flucytosine 1.7 g four times daily) and recurrent obstruction in the ventricular system requiring repeated neurosurgical interventions. However, full cure was achieved after seven months' hospital treatment.
Adolescent↗
Fast correction of cloud dose data files due to changes in dispersion parameters.
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Accidents↗
Impact of ozone mini-holes on the heterogeneous destruction of stratospheric ozone.
A comprehensive study of ozone mini-holes over the mid-latitudes of both hemispheres is presented, based on model simulations with the coupled climate-chemistry model ECHAM4.L39(DLR)/CHEM representing atmospheric conditions in 1960, 1980, 1990 and 2015. Ozone mini-holes are synoptic-scale regions of strongly reduced total ozone, directly associated with tropospheric weather systems. Mini-holes are supposed to have chemical and dynamical impacts on ozone levels. Since ozone levels over northern mid-latitudes show a negative trend of approximately -4%/decade and since it exists a negative correlation between total column ozone and erythemally active solar UV-radiation reaching the surface it is important to understand and assess the processes leading to the observed ozone decline. The simulated mini-hole events are validated with a mini-hole climatology based on daily ozone measurements with the TOMS (total ozone mapping spectrometer) instrument on the satellite Nimbus-7 between 1979 and 1993. Furthermore, possible trends in the event frequency and intensity over the simulation period are assessed. In the northern hemisphere the number of mini-hole events in early winter decreases between 1960 and 1990 and increases towards 2015. In the southern hemisphere a positive trend in mini-hole event frequency is detected between 1960 and 2015 in spring associated with the increasing Antarctic Ozone Hole. Finally, the impact of mini-holes on the stratospheric heterogeneous ozone chemistry is investigated. For this purpose, a computer-based detection routine for mini-holes was developed for the use in ECHAM4.L39(DLR)/CHEM. This method prevents polar stratospheric cloud formation and therefore heterogeneous ozone depletion inside mini-holes. Heterogeneous processes inside mini-holes amount to one third of heterogeneous ozone destruction in general over northern mid- and high-latitudes during winter (January-April) in the simulation.
Atmosphere↗
New high-flow "cloud" catheter for safer delivery of contrast material.
The authors describe a new angiographic catheter, which delivers equal flow rates through the side holes and reduced flow through the end hole compared with conventional catheters. Computer analysis of catheter-flow models revealed that placement of larger side holes proximally and smaller side holes distally produces more uniform flow rates out of the holes. This decreases the risk of potentially hazardous delivery of high-pressure jets of contrast material from the end hole. The flow pattern is so uniform that it resembles a cloud of contrast material on injection. This catheter design is particularly applicable for 3-5-F catheters, which require high-pressure injections. Clinical testing in 50 cases revealed no extravasations or unintentional selective injections with use of this catheter.
Angiography↗
Rationalization of membrane protein crystallization with polyethylene glycol using a simple depletion model.
Based on the importance of crystallizing membrane proteins in a rational way, cytochrome bc(1) complex (BC1) was crystallized using polyethylene glycol (PEG) as a sole crystallization agent. Interaction between protein-detergent complexes of BC1 was estimated by dynamic light scattering, and was compared with the numerical calculation using the Derjaguin-Landau-Verwey-Overbeek potential plus a depletion potential, without considering specific surface properties of the protein-detergent complexes. The experiments and calculation were found to be consistent and we obtained a relation between PEG molecular weight M and the range of depletion zone delta as delta approximately M(0.48+/-0.02). The stability of liquid phase of BC1 solutions was controlled by a ratio of (the range of depletion zone)/(the radius of a BC1 particle), which was consistent with recent theoretical predictions. The crystallization was most successful under a condition where the stability of the liquid phase changed from stable to unstable. The PEG molecular weight that fulfilled this condition coincided with the one used empirically to crystallize BC1 in the past by a number of groups. These results are compared to the fact that membrane proteins were often successfully crystallized close to the detergent cloud point.
Animals↗