464 research outputs found

    The utility of DNA microarrays for characterizing genotoxicity.

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    Microarrays provide an unprecedented opportunity for comprehensive concurrent analysis of thousands of genes. The global analysis of the response of genes to a toxic insult (toxicogenomics), as opposed to the historical method of examining a few select genes, provides a more complete picture of toxicologically significant events. Here we examine the utility of microarrays for providing mechanistic insights into the response of cells to DNA damage. Our data indicate that the value of the technology is in its potential to provide mechanistic insight into the mode of action of a genotoxic compound. Array-based expression profiling may be useful for differentiating compounds that interact directly with DNA from those compounds that are genotoxic via a secondary mechanism. As such, genomic microarrays may serve as a valuable alternative methodology that helps discriminate between these two classes of compounds. Key words: biomarkers, gene expression profile, genetic toxicology, mechanism of action, toxicogenomics

    Development of Magnetic Shape Memory Alloy Actuators for a Swashplateless Helicopter Rotor

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    Actuator concepts utilizing NiMnGa, ferromagnetic shape memory alloy are investigated for potential use on a smart rotor for trailing edge flap actuation. With their high energy density, large dynamic stroke, and wide operating bandwidth, ferromagnetic shape memory alloys (FSMA) like NiMnGa, seem like attractive candidates for smart rotor actuators, potentially able to fulfill the requirements for both primary rotor control and vibration suppression. However, because of the recent discovery of the material, current experimental data and analytical tools are limited. To rectify these shortcomings, an extensive set of detailed experiments were conducted on samples of NiMnGa to characterize the response of the alloy for a wide variety of mechanical and magnetic loading conditions. Measurements of the material performance parameters such as power density, damping properties, magneto-mechanical coupling, and transduction efficiency were included. Once characterized, the experimental data were used to develop a series of analytical tools to predict the behavior of the material. A model, developed in parallel to thermal shape memory alloy models is proposed to predict the quasi-static stress-strain behavior. A simple, low frequency, parameter based model was also developed to predict the alloy's dynamic strain response. A method for developing conceptual actuators utilizing NiMnGa as the actuation element was proposed. This approach incorporates experimental data into a process that down-selects a series of possible actuator configurations to obtain a single configuration optimized for volumetric and weight considerations. The proposed actuator was designed to deliver 2 mm of stroke and 60 N of force at an actuation frequency of 50 Hz. However, to generate the 1.0 T magnetic field, the actuator mass was determined to be 2.8 kg and required a minimum of 320 Watts of power for operation. The mass of the NiMnGa element was only 18.3 g. It was concluded that although the NiMnGa alloy was capable of meeting the trailing edge flap actuation requirements, the material is not suitable in its present form for this application because of weight and power consumption issues. The magnetic field requirements must be reduced to improve the utility of the material for rotorcraft applications

    Low-Mach-number turbulence in interstellar gas revealed by radio polarization gradients

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    The interstellar medium of the Milky Way is multi-phase, magnetized and turbulent. Turbulence in the interstellar medium produces a global cascade of random gas motions, spanning scales ranging from 100 parsecs to 1000 kilometres. Fundamental parameters of interstellar turbulence such as the sonic Mach number (the speed of sound) have been difficult to determine because observations have lacked the sensitivity and resolution to directly image the small-scale structure associated with turbulent motion. Observations of linear polarization and Faraday rotation in radio emission from the Milky Way have identified unusual polarized structures that often have no counterparts in the total radiation intensity or at other wavelengths, and whose physical significance has been unclear. Here we report that the gradient of the Stokes vector (Q,U), where Q and U are parameters describing the polarization state of radiation, provides an image of magnetized turbulence in diffuse ionized gas, manifested as a complex filamentary web of discontinuities in gas density and magnetic field. Through comparison with simulations, we demonstrate that turbulence in the warm ionized medium has a relatively low sonic Mach number, M_s <~ 2. The development of statistical tools for the analysis of polarization gradients will allow accurate determinations of the Mach number, Reynolds number and magnetic field strength in interstellar turbulence over a wide range of conditions.Comment: 5 pages, 3 figures, published in Nature on 13 Oct 201

    Withdrawal of parenteral phenobarbitone - implications for resource-poor countries

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    Parenteral phenobarbitone is an integral part of the management of status epilepticus, especially in the context of resource-poor countries. It is highly effective at controlling seizures. It is safe, cheap, can be given by rapid intravenous push or intramuscular route, boluses can be repeated, and it is recommended as part of the Advanced Paediatric Life Support guidelines. The proposed alternatives lack efficacy, practicality and/or place the child in status epilepticus at risk of respiratory compromise. The impact of the loss of parenteral phenobarbitone would be increased cardiac complications, lack of early seizure control, prolonged seizures resulting in brain damage and systemic complications. Increased numbers of patients will require artificial ventilation in centres without facilities, and centres with facilities will be unable to cope with the load of ventilated patients because of lack of safe transport systems and bed space

    The Extinction and Distance of Maffei 1

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    We have obtained low- and high-resolution spectra of the core of the highly-reddened elliptical galaxy Maffei 1. From these data, we have obtained the first measurement of the Mg2 index, and have measured the velocity dispersion and radial velocity with improved accuracy. To evaluate the extinction, a correlation between the Mg2 index and effective V-I colour has been established for elliptical galaxies. Using a new method for correcting for effective wavelength shifts, we find A_V = 4.67 +/- 0.19 mag, which is lower by 0.4 mag than previously thought. To establish the distance, the Fundamental Plane for elliptical galaxies has been constructed in I. The velocity dispersion of Maffei 1, measured to be 186.8 +/- 7.4 km/s, in combination with modern wide-field photometry in I, leads to a distance of 2.92 +/- 0.37 Mpc. The Dn-sigma relation, which is independently calibrated, gives 3.08 +/- 0.85 Mpc and 3.23 +/- 0.67 Mpc from photometry in B and K`, respectively. The weighted mean of the three estimates is 3.01 +/- 0.30 Mpc. The distance and luminosity make Maffei 1 the nearest giant elliptical galaxy. The radial velocity of Maffei 1 is +66.4 +/- 5.0 km/s, significantly higher than the accepted value of -10 km/s. The Hubble distance corresponding to the mean velocity of Maffei 1, Maffei 2 and IC342 is 3.5 Mpc. Thus, it is unlikely that Maffei 1 has had any influence on Local Group dynamics

    The Australia Telescope 20GHz (AT20G) Survey: analysis of the extragalactic source sample

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    The Australia Telescope 20 GHz (AT20G) survey is a blind survey of the whole Southern sky at 20 GHz with follow-up observations at 4.8, 8.6, and 20 GHz carried out with the Australia Telescope Compact Array (ATCA). In this paper we present an analysis of radio spectral properties in total intensity and polarisation, sizes, optical identifications, and redshifts of the sample of the 5808 extragalactic sources in the survey catalogue of confirmed sources over the whole Southern sky excluding the strip at Galactic latitude |b|<1.5deg. The sample has a flux density limit of 40 mJy. Completeness has been measured as a function of scan region and flux density. Averaging over the whole survey area the follow-up survey is 78% complete above 50mJy and 93% complete above 100mJy. 3332 sources with declination <-15deg have good quality almost simultaneous observations at 4.8, 8.6, and 20GHz. The spectral analysis shows that the sample is dominated by flat-spectrum sources. The fraction of flat-spectrum sources decreases from 81% for 20GHz flux densities S>500mJy, to 60% for S<100mJy. There is also a clear spectral steepening at higher frequencies with the median spectral index decreasing from -0.16 between 4.8 and 8.6GHz to -0.28 between 8.6 and 20GHz. Simultaneous observations in polarisation are available for all the sources at all the frequencies. 768 sources have a good quality detection of polarised flux density at 20GHz; 467 of them were also detected in polarisation at 4.8 and/or at 8.6GHz so that it has been possible to compare the spectral behaviour in total intensity and polarisation. We have found that the polarised fraction increases slightly with frequency and decreases with flux density. Cross matches and comparisons have been made with other catalogues at lower radio frequencies, and in the optical, X-ray and gamma-ray bands. Redshift estimates are available for 825 sources.Comment: 15 pages, 16 figures, accepted for publication in MNRA

    Klippel-Trenaunay-Weber Syndrome: association of operative treatment with foam sclerotherapy

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    The Klippel-Trenaunay-Weber Syndrome is the association of hemangioma, venous ectasia, and hypertrophy of the affected body segment. We report the case of a 39-year-old male followed-up since 1993 due to onset of symptoms in the left lower limb. He was treated only with the use of elastic stockings and general measures. Over the years, he had worsening of venous stasis, of bone hypertrophy, and of skin hyperpigmentation. Color-coded Doppler ultrasonography of the lower limbs showed patency of the deep venous system, venous overflow, segmentar insufficiency of the greater saphenous vein with signs of thrombophlebitis, and insufficient tributary veins. In order to improve venous stasis, ligation of the left sapheno-femoral junction and retrograde foam sclerotherapy (polidocanol 3%) with resection of tributary veins were performed. The patient was discharged in the first postoperative day and has been followed as an outpatient, presenting significant improvement of the symptoms.A Síndrome de Klippel-Trenaunay-Weber representa a associação de hemangiomas planos, ectasias venosas e hipertrofia do segmento corpóreo afetado. Apresenta-se o caso de um paciente de 39 anos, sexo masculino, seguido desde 1993 no serviço da Disciplina de Cirurgia Vascular da Escola Paulista de Medicina (UNIFESP), por quadro inicial da síndrome em membro inferior esquerdo. O paciente foi tratado apenas por elastocompressão e medidas gerais. Neste período, ele evoluiu com piora da estase venosa, da hipertrofia óssea e da hiperpigmentação de pele. Na ultrassonografia Doppler colorida venosa dos membros inferiores havia perviedade do sistema venoso profundo, hiperfluxo venoso, insuficiência segmentar de veia safena magna com sinais de tromboflebite e tributárias insuficientes. Indicou-se, para a melhora da estase venosa, ligadura da junção safeno-femoral esquerda e escleroterapia (polidocanol 3%) retrógrada da mesma, com exérese das ectasias venosas. O paciente recebeu alta hospitalar no primeiro dia pós-operatório e atualmente está em acompanhamento ambulatorial com melhora significativa dos sintomas.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

    Comparison of structural changes in nodding syndrome and other epilepsies associated with Onchocerca volvulus

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    Background and Objective: Nodding syndrome (NS) is a unique childhood-onset epileptic disorder that occurs predominantly in several regions of sub-Saharan Africa. The disease has been associated with Onchocerca volvulus (Ov)–induced immune responses and possible cross-reactivity with host proteins. The aim of this study was to compare structural changes in the brain on MRI between NS and other forms of onchocerciasis-associated epilepsies (OAEs) and to relate structural changes to the Ov-induced immune responses and level of disability. Methods: Thirty-nine children with NS and 14 age-matched participants with other forms of OAE from an endemic region in Uganda underwent detailed clinical examination, serologic evaluation (including Ov-associated antibodies to Ov-16 and Hu-leiomodin-1) and quantitative volumetric analysis of brain MRIs (1.5 T scanner) using Neuroreader, a cloud-based software. Results: Cerebral and cerebellar atrophy were the predominant features in both NS and OAE. On quantitative volumetric analysis, participants with NS had larger ventricular volumes compared with participants with OAE, indicative of increased global cortical atrophy (pcorr = 0.036). Among children with NS, severe disability correlated with higher degree of atrophy in the gray matter volume (pcorr = 0.009) and cerebellar volume (pcorr = 0.009). NS cases had lower anti-Ov-16 IgG signal-to-noise ratios than the OAE cases (p < 0.01), but no difference in the levels of the Hu-leiomodin-1 antibodies (p = 0.64). The levels of Ov-associated antibodies did not relate to the degree of cerebral or cerebellar atrophy in either NS or OAE cases. Discussion: This is the first study to show that cerebral and cerebellar atrophy correlated with the severity of NS disability, providing an imaging marker for these endemic epileptic disorders that until now have remained poorly characterized. Both NS and OAE have cerebral and cerebellar atrophy, and the levels of Ov-associated antibodies do not seem to be related to the structural changes on MRI
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