2,681 research outputs found

    Gene identification for the cblD defect of vitamin B12 metabolism

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    Background Vitamin B12 (cobalamin) is an essential cofactor in several metabolic pathways. Intracellular conversion of cobalamin to its two coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for the homeostasis of methylmalonic acid and homocysteine. Nine defects of intracellular cobalamin metabolism have been defined by means of somatic complementation analysis. One of these defects, the cblD defect, can cause isolated methylmalonic aciduria, isolated homocystinuria, or both. Affected persons present with multisystem clinical abnormalities, including developmental, hematologic, neurologic, and metabolic findings. The gene responsible for the cblD defect has not been identified. Methods We studied seven patients with the cblD defect, and skin fibroblasts from each were investigated in cell culture. Microcell-mediated chromosome transfer and refined genetic mapping were used to localize the responsible gene. This gene was transfected into cblD fibroblasts to test for the rescue of adenosylcobalamin and methylcobalamin synthesis. Results The cblD gene was localized to human chromosome 2q23.2, and a candidate gene, designated MMADHC (methylmalonic aciduria, cblD type, and homocystinuria), was identified in this region. Transfection of wild-type MMADHC rescued the cellular phenotype, and the functional importance of mutant alleles was shown by means of transfection with mutant constructs. The predicted MMADHC protein has sequence homology with a bacterial ATP-binding cassette transporter and contains a putative cobalamin binding motif and a putative mitochondrial targeting sequence. Conclusions Mutations in a gene we designated MMADHC are responsible for the cblD defect in vitamin B12 metabolism. Various mutations are associated with each of the three biochemical phenotypes of the disorder

    Planetary Radio Interferometry and Doppler Experiment (PRIDE) Technique: a Test Case of the Mars Express Phobos Fly-by. 2. Doppler tracking: Formulation of observed and computed values, and noise budget

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    Context. Closed-loop Doppler data obtained by deep space tracking networks (e.g., NASA's DSN and ESA's Estrack) are routinely used for navigation and science applications. By "shadow tracking" the spacecraft signal, Earth-based radio telescopes involved in Planetary Radio Interferometry and Doppler Experiment (PRIDE) can provide open-loop Doppler tracking data when the dedicated deep space tracking facilities are operating in closed-loop mode only. Aims. We explain in detail the data processing pipeline, discuss the capabilities of the technique and its potential applications in planetary science. Methods. We provide the formulation of the observed and computed values of the Doppler data in PRIDE tracking of spacecraft, and demonstrate the quality of the results using as a test case an experiment with ESA's Mars Express spacecraft. Results. We find that the Doppler residuals and the corresponding noise budget of the open-loop Doppler detections obtained with the PRIDE stations are comparable to the closed-loop Doppler detections obtained with the dedicated deep space tracking facilities

    Computer modeling of large asteroid impacts into continental and oceanic sites: Atmospheric, cratering, and ejecta dynamics

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    Numerous impact cratering events have occurred on the Earth during the last several billion years that have seriously affected our planet and its atmosphere. The largest cratering events, which were caused by asteroids and comets with kinetic energies equivalent to tens of millions of megatons of TNT, have distributed substantial quantities of terrestrial and extraterrestrial material over much or all of the Earth. In order to study a large-scale impact event in detail, computer simulations were completed that model the passage of a 10 km-diameter asteroid through the Earth's atmosphere and the subsequent cratering and ejecta dynamics associated with impact of the asteroid into two different targets, i.e., an oceanic site and a continental site. The calcuations were designed to broadly represent giant impact events that have occurred on the Earth since its formation and specifically represent an impact cratering event proposed to have occurred at the end of Cretaceous time. Calculation of the passage of the asteroid through a U.S. Standard Atmosphere showed development of a strong bow shock that expanded radially outward. Behind the shock front was a region of highly shock compressed and intensely heated air. Behind the asteroid, rapid expansion of this shocked air created a large region of very low density that also expanded away from the impact area. Calculations of the cratering events in both the continental and oceanic targets were carried to 120 s. Despite geologic differences, impacts in both targets developed comparable dynamic flow fields, and by approx. 29 s similar-sized transient craters approx. 39 km deep and approx. 62 km across had formed. For all practical purposes, the atmosphere was nearly completely removed from the impact area for tens of seconds, i.e., air pressures were less than fractions of a bar out to ranges of over 50 km. Consequently, much of the asteroid and target materials were ejected upward into a near vacuum. Effects of secondary volcanism and return of the ocean over hot oceanic crater floor could also be expected to add substantial solid and vaporized material to the atmosphere, but these conditions were not studied

    Applying machine learning to the problem of choosing a heuristic to select the variable ordering for cylindrical algebraic decomposition

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    Cylindrical algebraic decomposition(CAD) is a key tool in computational algebraic geometry, particularly for quantifier elimination over real-closed fields. When using CAD, there is often a choice for the ordering placed on the variables. This can be important, with some problems infeasible with one variable ordering but easy with another. Machine learning is the process of fitting a computer model to a complex function based on properties learned from measured data. In this paper we use machine learning (specifically a support vector machine) to select between heuristics for choosing a variable ordering, outperforming each of the separate heuristics.Comment: 16 page

    Microaerobic Conditions Are Required for Magnetite Formation Within \u3ci\u3eAquaspirillum magnetotacticum\u3c/i\u3e

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    The amount of magnetite (Fe3O4) within magnetosomes of the microaerophilic bacterium Aquaspirillum magnetotacticum varies with oxygen and nitrogen supply. The development of optical methods for directly measuring cell magnetism in culture samples has enabled us to quantitate bacterial Fe3O4 yields. We measured final cell yields, average cell magnetic moments, and magnetosome yields of growing cells. Cultures were grown with NO3-, NH4+, or both, in sealed, unshaken vials with initial headspace Po2 values ranging from 0 (trace) to 21 kPa. More than 50% of cells had detectable magnetosomes only when grown in the range of 0.5-5.0 kPa O2. Optimum cell magnetism (and Fe3O4 formation) occurred under microaerobic conditions (initial headspace Po2 of 0.5-1 kPa) regardless of the N source. At optimal conditions for Fe3O4 formation, denitrifying cultures produced more of this mineral than those growing with O2 as the sole terminal electron acceptor. This suggests that competition for O2 exists between processes involving respiratory electron disposal and Fe3O4 formation. Oxygen may also be required for Fe3O4 formation by other species of magnetotactic bacteria. Bacterial Fe3O4 appears to persist in sediments after death and lysis of cells. The presence of bacterial Fe3O4 in the fossil and paleomagnetic records may be of use as a retrospective indicator of sedimentation that has occurred in microaerobic waters

    The uses and functions of ageing celebrity war reporters

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    This article starts from the premise that recognition of professional authority and celebrity status depends on the embodiment and performance of field-specific dispositional practices: there’s no such thing as a natural, though we often talk about journalistic instinct as something someone simply has or doesn’t have. Next, we have little control over how we are perceived by peers and publics, and what we think are active positioning or subjectifying practices are in fact, after Bourdieu, revelations of already-determined delegation. The upshot is that two journalists can arrive at diametrically opposed judgements on the basis of observation of the same actions of a colleague, and as individuals we are blithely hypocritical in forming (or reciting) evaluations of the professional identity of celebrities. Nowhere is this starker than in the discourse of age-appropriate behaviour, which this paper addresses using the examples of ‘star’ war reporters John Simpson, Kate Adie and Martin Bell. A certain rough-around-the-edges irreverence is central to dispositional authenticity amongst war correspondents, and for ageing hacks this incorporates gendered attitudes to sex and alcohol as well as indifference to protocol. And yet perceived age-inappropriate sexual behaviour is also used to undermine professional integrity, and the paper ends by outlining the phenomenological context that makes possible this effortless switching between amoral and moralising recognition by peers and audiences alike

    Protease nexin-1 activity in cultured Schwann cells

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    We report that protease nexin-1 (PN-1), a serine protease inhibitor known to have neurite-promoting effects, is made by Schwann cells in tissue culture. Three modalities have been used to demonstrate the presence of PN-1 in Schwann cell cultures. Immunostaining of the cultures with anti-PN-1 antibody gives positive staining over cells and matrix. Western blots of Schwann cell conditioned medium (CM) using anti-PN-1 antibody show a band that co-migrates with the PN-1 standard at 45 kDa. Biochemical assay for protease inhibitory activity shows that CM inhibits thrombin activity in a calorimetric assay. The CM-mediated inhibition of thrombin is reversed if the CM is pre-incubated with anti-PN-1 antibody.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29228/1/0000283.pd

    Venus Express radio occultation observed by PRIDE

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    Context. Radio occultation is a technique used to study planetary atmospheres by means of the refraction and absorption of a spacecraft carrier signal through the atmosphere of the celestial body of interest, as detected from a ground station on Earth. This technique is usually employed by the deep space tracking and communication facilities (e.g., NASA's Deep Space Network (DSN), ESA's Estrack). Aims. We want to characterize the capabilities of the Planetary Radio Interferometry and Doppler Experiment (PRIDE) technique for radio occultation experiments, using radio telescopes equipped with Very Long Baseline Interferometry (VLBI) instrumentation. Methods. We conducted a test with ESA's Venus Express (VEX), to evaluate the performance of the PRIDE technique for this particular application. We explain in detail the data processing pipeline of radio occultation experiments with PRIDE, based on the collection of so-called open-loop Doppler data with VLBI stations, and perform an error propagation analysis of the technique. Results. With the VEX test case and the corresponding error analysis, we have demonstrated that the PRIDE setup and processing pipeline is suited for radio occultation experiments of planetary bodies. The noise budget of the open-loop Doppler data collected with PRIDE indicated that the uncertainties in the derived density and temperature profiles remain within the range of uncertainties reported in previous Venus' studies. Open-loop Doppler data can probe deeper layers of thick atmospheres, such as that of Venus, when compared to closed-loop Doppler data. Furthermore, PRIDE through the VLBI networks around the world, provides a wide coverage and range of large antenna dishes, that can be used for this type of experiments

    Beyond Hebb: Exclusive-OR and Biological Learning

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    A learning algorithm for multilayer neural networks based on biologically plausible mechanisms is studied. Motivated by findings in experimental neurobiology, we consider synaptic averaging in the induction of plasticity changes, which happen on a slower time scale than firing dynamics. This mechanism is shown to enable learning of the exclusive-OR (XOR) problem without the aid of error back-propagation, as well as to increase robustness of learning in the presence of noise.Comment: 4 pages RevTeX, 2 figures PostScript, revised versio
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