Pharmacokinetics of orally administered tetrahydrobiopterin in patients with phenylalanine hydroxylase deficiency

Summary: The oral loading test with tetrahydrobiopterin (BH4) is used to discriminate between variants of hyperphenylalaninaemia and to detect BH4-responsive patients. The outcome of the loading test depends on the genotype, dosage of BH4, and BH4 pharmacokinetics. A total of 71 patients with hyperphenylalaninaemia (mild to classic) were challenged with BH4 (20 mg/kg) according to different protocols (1 × 20 mg or 2 × 20 mg) and blood BH4 concentrations were measured in dried blood spots at different time points (T0, T2, T4, T8, T12, T24, T32 and T48 h). Maximal BH4 concentrations (median 22.69 nmol/g Hb) were measured 4 h after BH4 administration in 63 out of 71 patients. Eight patients presented with maximal BH4 concentrations ∼44% higher at 8 h than at 4 h. After 24 h, BH4 blood concentrations dropped to 11% of maximal values. This profile was similar using different protocols. The following pharmacokinetic parameters were calculated for BH4 in blood: t max = 4 h, AUC (T0−32) = 370 nmol × h/g Hb, and t 1/2 for absorption (1.1 h), distribution (2.5 h), and elimination (46.0 h) phases. Maximal BH4 blood concentrations were not significantly lower in non-responders and there was no correlation between blood concentrations and responsiveness. Of mild PKU patients, 97% responded to BH4 administration, while one was found to be a non-responder. Only 10/19 patients (53%) with Phe concentrations of 600-1200 μmol/L responded to BH4 administration, and of the patients with the severe classical phenotype (blood Phe > 1200 μmol/L) only 4 out of 17 patient responded. An additional 36 patients with mild hyperphenylalaninaemia (HPA) who underwent the combined loading test with Phe+BH4 were all responders. Slow responders and non-responders were found in all groups of HP

Screening of melon genotypes for resistance to vegetable leafminer and your phenotypic correlations with colorimetry.

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Dynamics of an Intruder in Dense Granular Fluids

We investigate the dynamics of an intruder pulled by a constant force in a dense two-dimensional granular fluid by means of event-driven molecular dynamics simulations. In a first step, we show how a propagating momentum front develops and compactifies the system when reflected by the boundaries. To be closer to recent experiments \cite{candelier2010journey,candelier2009creep}, we then add a frictional force acting on each particle, proportional to the particle's velocity. We show how to implement frictional motion in an event-driven simulation. This allows us to carry out extensive numerical simulations aiming at the dependence of the intruder's velocity on packing fraction and pulling force. We identify a linear relation for small and a nonlinear regime for high pulling forces and investigate the dependence of these regimes on granular temperature

Rotation and X-ray emission from protostars

The ASCA satellite has recently detected variable hard X-ray emission from two Class I protostars in the rho Oph cloud, YLW15 (IRS43) and WL6, with a characteristic time scale ~20h. In YLW15, the X-ray emission is in the form of quasi-periodic energetic flares, which we explain in terms of strong magnetic shearing and reconnection between the central star and the accretion disk. In WL6, X-ray flaring is rotationally modulated, and appears to be more like the solar-type magnetic activity ubiquitous on T Tauri stars. We find that YLW15 is a fast rotator (near break-up), while WL6 rotates with a significantly longer period. We derive a mass M_\star ~ 2 M_\odot and \simlt 0.4 M_\odot for the central stars of YLW15 and WL6 respectively. On the long term, the interactions between the star and the disk results in magnetic braking and angular momentum loss of the star. On time scales t_{br} ~ a few 10^5 yrs, i.e., of the same order as the estimated duration of the Class~I protostar stage. Close to the birthline there must be a mass-rotation relation, t_{br} \simpropto M_\star, such that stars with M_\star \simgt 1-2 M_\odot are fast rotators, while their lower-mass counterparts have had the time to spin down. The rapid rotation and strong star-disk magnetic interactions of YLW15 also naturally explain the observation of X-ray ``superflares''. In the case of YLW15, and perhaps also of other protostars, a hot coronal wind (T~10^6 K) may be responsible for the VLA thermal radio emission. This paper thus proposes the first clues to the rotation status and evolution of protostars.Comment: 13 pages with 6 figures. To be published in ApJ (April 10, 2000 Part 1 issue

Structure and Stability of Keplerian MHD Jets

MHD jet equilibria that depend on source properties are obtained using a simplified model for stationary, axisymmetric and rotating magnetized outflows. The present rotation laws are more complex than previously considered and include a Keplerian disc. The ensuing jets have a dense, current-carrying central core surrounded by an outer collar with a return current. The intermediate part of the jet is almost current-free and is magnetically dominated. Most of the momentum is located around the axis in the dense core and this region is likely to dominate the dynamics of the jet. We address the linear stability and the non-linear development of instabilities for our models using both analytical and 2.5-D numerical simulation's. The instabilities seen in the simulations develop with a wavelength and growth time that are well matched by the stability analysis. The modes explored in this work may provide a natural explanation for knots observed in astrophysical jets.Comment: 35 pages, accepted by the Ap

The Photon Dominated Region in the IC 348 molecular cloud

In this paper we discuss the physical conditions of clumpy nature in the IC 348 molecular cloud. We combine new observations of fully sampled maps in [C I] at 492 GHz and 12CO 4--3, taken with the KOSMA 3 m telescope at about 1' resolution, with FCRAO data of 12CO 1--0, 13CO 1--0 and far-infrared continuum data observed by HIRES/IRAS. To derive the physical parameters of the region we analyze the three different line ratios. A first rough estimate of abundance is obtained from an LTE analysis. To understand the [C I] and CO emission from the PDRs in IC 348, we use a clumpy PDR model. With an ensemble of identical clumps, we constrain the total mass from the observed absolute intensities. Then we apply a more realistic clump distribution model with a power law index of 1.8 for clump-mass spectrum and a power law index of 2.3 for mass-size relation. We provide detailed fits to observations at seven representative positions in the cloud, revealing clump densities between 4 10$^{4}$ cm$^{-3}$ and 4 10$^{5}$ cm$^{-3}$ and C/CO column density ratios between 0.02 and 0.26. The derived FUV flux from the model fit is consistent with the field calculated from FIR continuum data, varying between 2 and 100 Draine units across the cloud. We find that both an ensemble of identical clumps and an ensemble with a power law clump mass distribution produce line intensities which are in good agreement (within a factor ~ 2) with the observed intensities. The models confirm the anti-correlation between the C/CO abundance ratio and the hydrogen column density found in many regions.Comment: 11 pages, 8 figures, accepted by A&

Efficient Passive ICS Device Discovery and Identification by MAC Address Correlation

Owing to a growing number of attacks, the assessment of Industrial Control Systems (ICSs) has gained in importance. An integral part of an assessment is the creation of a detailed inventory of all connected devices, enabling vulnerability evaluations. For this purpose, scans of networks are crucial. Active scanning, which generates irregular traffic, is a method to get an overview of connected and active devices. Since such additional traffic may lead to an unexpected behavior of devices, active scanning methods should be avoided in critical infrastructure networks. In such cases, passive network monitoring offers an alternative, which is often used in conjunction with complex deep-packet inspection techniques. There are very few publications on lightweight passive scanning methodologies for industrial networks. In this paper, we propose a lightweight passive network monitoring technique using an efficient Media Access Control (MAC) address-based identification of industrial devices. Based on an incomplete set of known MAC address to device associations, the presented method can guess correct device and vendor information. Proving the feasibility of the method, an implementation is also introduced and evaluated regarding its efficiency. The feasibility of predicting a specific device/vendor combination is demonstrated by having similar devices in the database. In our ICS testbed, we reached a host discovery rate of 100% at an identification rate of more than 66%, outperforming the results of existing tools.Comment: http://dx.doi.org/10.14236/ewic/ICS2018.

an overview of the MHONGOOSE survey: Observing nearby galaxies with MeerKAT

© Copyright owned by the author(s). MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with H I masses from ∼ 106 to ∼ 1011 M, and luminosities from MR ∼ 12 to MR ∼ −22. The sample is selected to uniformly cover the available range in log(MHI). Our extremely deep observations, down to H I column density limits of well below 1018 cm−2 — or a few hundred times fainter than the typical H I disks in galaxies — will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modeling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT’s capabilities

The JCMT Gould Belt Survey: Evidence for radiative heating in Serpens MWC 297 and its influence on local star formation

We present SCUBA-2 450micron and 850micron observations of the Serpens MWC 297 region, part of the JCMT Gould Belt Survey of nearby star-forming regions. Simulations suggest that radiative feedback influences the star-formation process and we investigate observational evidence for this by constructing temperature maps. Maps are derived from the ratio of SCUBA-2 fluxes and a two component model of the JCMT beam for a fixed dust opacity spectral index of beta = 1.8. Within 40 of the B1.5Ve Herbig star MWC 297, the submillimetre fluxes are contaminated by free-free emission with a spectral index of 1.03+-0.02, consistent with an ultra-compact HII region and polar winds/jets. Contamination accounts for 73+-5 per cent and 82+-4 per cent of peak flux at 450micron and 850micron respectively. The residual thermal disk of the star is almost undetectable at these wavelengths. Young Stellar Objects are confirmed where SCUBA-2 850micron clumps identified by the fellwalker algorithm coincide with Spitzer Gould Belt Survey detections. We identify 23 objects and use Tbol to classify nine YSOs with masses 0.09 to 5.1 Msun. We find two Class 0, one Class 0/I, three Class I and three Class II sources. The mean temperature is 15+-2K for the nine YSOs and 32+-4K for the 14 starless clumps. We observe a starless clump with an abnormally high mean temperature of 46+-2K and conclude that it is radiatively heated by the star MWC 297. Jeans stability provides evidence that radiative heating by the star MWC 297 may be suppressing clump collapse.Comment: 24 pages, 13 figures, 7 table