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

Boyle's law and gravitational instability

We have re-examined the classical problem of the macroscopic equation of state for a hydrostatic isothermal self-gravitating gas cloud bounded by an external medium at constant pressure. We have obtained analytical conditions for its equilibrium and stability without imposing any specific shape and symmetry to the cloud density distribution. The equilibrium condition can be stated in the form of an upper limit to the cloud mass; this is found to be inversely proportional to the power 3/2 of a form factor \mu characterizing the shape of the cloud. In this respect, the spherical solution, associated with the maximum value of the form factor, \mu = 1, turns out to correspond to the shape that is most difficult to realize. Surprisingly, the condition that defines the onset of the Bonnor instability (or gravothermal catastrophe) can be cast in the form of an upper limit to the density contrast within the cloud that is independent of the cloud shape. We have then carried out a similar analysis in the two-dimensional case of infinite cylinders, without assuming axisymmetry. The results obtained in this paper generalize well-known results available for spherical or axisymmetric cylindrical isothermal clouds that have had wide astrophysical applications, especially in the study of the interstellar medium.Comment: 9 pages, 2 figures, to appear in A&

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

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.

Comparing star formation models with interferometric observations of the protostar NGC 1333 IRAS 4A. I. Magnetohydrodynamic collapse models

Observations of dust polarized emission toward star forming regions trace the magnetic field component in the plane of the sky and provide constraints to theoretical models of cloud collapse. We compare high-angular resolution observations of the submillimeter polarized emission of the low-mass protostellar source NGC 1333 IRAS 4A with the predictions of three different models of collapse of magnetized molecular cloud cores. We compute the Stokes parameters for the dust emission for the three models. We then convolve the results with the instrumental response of the Submillimeter Array observation toward IRAS 4A. Finally, we compare the synthetic maps with the data, varying the model parameters and orientation, and we assess the quality of the fit by a \chi^2 analysis. High-angular resolution observations of polarized dust emission can constraint the physical properties of protostars. In the case of IRAS 4A, the best agreements with the data is obtained for models of collapse of clouds with mass-to-flux ratio >2 times the critical value, initial uniform magnetic field of strength ~0.5 mG, and age of the order of a few 10^4 yr since the onset of collapse. Magnetic dissipation, if present, is found to occur below the resolution level of the observations. Including a previously measured temperature profile of IRAS 4A leads to a more realistic morphology and intensity distribution. We also show that ALMA has the capability of distinguishing among the three different models adopted in this work. Our results are consistent with the standard theoretical scenario for the formation of low-mass stars, where clouds initially threaded by large-scale magnetic fields become unstable and collapse, trapping the field in the nascent protostar and the surrounding circumstellar disk. In the collapsing cloud, the dynamics is dominated by gravitational and magnetic forces.Comment: Accepted for publication in Astronomy And Astrophysics. 14 pages, 11 figures, 3 tables. Several the figures are shown at low resolutio

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

TADPOL: A 1.3 mm Survey of Dust Polarization in Star-forming Cores and Regions

We present {\lambda}1.3 mm CARMA observations of dust polarization toward 30 star-forming cores and 8 star-forming regions from the TADPOL survey. We show maps of all sources, and compare the ~2.5" resolution TADPOL maps with ~20" resolution polarization maps from single-dish submillimeter telescopes. Here we do not attempt to interpret the detailed B-field morphology of each object. Rather, we use average B-field orientations to derive conclusions in a statistical sense from the ensemble of sources, bearing in mind that these average orientations can be quite uncertain. We discuss three main findings: (1) A subset of the sources have consistent magnetic field (B-field) orientations between large (~20") and small (~2.5") scales. Those same sources also tend to have higher fractional polarizations than the sources with inconsistent large-to-small-scale fields. We interpret this to mean that in at least some cases B-fields play a role in regulating the infall of material all the way down to the ~1000 AU scales of protostellar envelopes. (2) Outflows appear to be randomly aligned with B-fields; although, in sources with low polarization fractions there is a hint that outflows are preferentially perpendicular to small-scale B-fields, which suggests that in these sources the fields have been wrapped up by envelope rotation. (3) Finally, even at ~2.5" resolution we see the so-called "polarization hole" effect, where the fractional polarization drops significantly near the total intensity peak. All data are publicly available in the electronic edition of this article.Comment: 53 pages, 37 figures -- main body (13 pp., 3 figures), source maps (32 pp., 34 figures), source descriptions (8 pp.). Accepted by the Astrophysical Journal Supplemen

Misalignment of magnetic fields and outflows in protostellar cores

We present results of λ1.3 mm dust-polarization observations toward 16 nearby, low-mass protostars, mapped with ∼2.″5 resolution at CARMA. The results show that magnetic fields in protostellar cores on scales of ∼1000 AU are not tightly aligned with outflows from the protostars. Rather, the data are consistent with scenarios where outflows and magnetic fields are preferentially misaligned (perpendicular), or where they are randomly aligned. If one assumes that outflows emerge along the rotation axes of circumstellar disks, and that the outflows have not disrupted the fields in the surrounding material, then our results imply that the disks are not aligned with the fields in the cores from which they forme

The JCMT Gould Belt Survey: properties of star-forming filaments in Orion A North

We develop and apply a Hessian-based filament detection algorithm to submillimetre continuum observations of Orion A North. The resultant filament radial density profiles are fitted with beam-convolved line-of-sight Plummer-profiles using Markov chain Monte Carlo techniques. The posterior distribution of the radial decay parameter demonstrates that the majority of filaments exhibit p = 1.5–3, with a mode at p = 2.2, suggesting deviation from the Ostriker p = 4 isothermal, equilibrium, self-gravitating cylinder. The spatial distribution of young stellar objects relative to the high column density filaments is investigated, yielding a lower limit on the star-forming age of the integral-shaped filament ∼1.4 Myr. Additionally, inferred lifetimes of filaments are examined which suggest long-term filament accretion, varying rates of star formation, or both. Theoretical filament stability measures are determined with the aid of HARP C18O J = 3–2 observations and indicate that the majority of filaments are gravitationally subcritical, despite the presence of young protostars. The results from this investigation are consistent with the one-dimensional accretion flow filament model recently observed in numerical simulations