Ammonia toxicity to the brain and creatine.

Symptoms of hyperammonemia are age-dependent and some are reversible. Multiple mechanisms are involved. Hyperammonemia increases the uptake of tryptophan into the brain by activation of the L-system carrier while brain glutamine plays a still undefined role. The uptake of tryptophan by the brain is enhanced when the plasma levels of branched-chain amino acids competing with the other large neutral amino acids are low. Hyperammonemia increases the utilization of branched-chain amino acids in muscle when ketoglutarate is low, and this is further enhanced by glutamine depletion (as a result of therapy with ammonia scavengers like phenylbutyrate). Anorexia, most likely a serotoninergic symptom, might further aggravate the deficiency of indispensable amino acids (e.g., branched-chain and arginine). The role of increased glutamine production in astrocytes and the excitotoxic and metabotropic effects of increased extracellular glutamate have been extensively investigated and found to differ between models of acute and chronic hyperammonemia. Using an in vitro model of cultured embryonic rat brain cell aggregates, we studied the role of creatine in ammonia toxicity. Cultures exposed to ammonia before maturation showed impaired cholinergic axonal growth accompanied by a decrease of creatine and phosphocreatine, a finding not observed in mature cultures. By using different antibodies, we have shown that the phosphorylated form of the intermediate neurofilament protein is affected. Adding creatine to the culture medium partially prevents impairment of axonal growth and the presence of glia in the culture is a precondition for this protective effect. Adequate arginine substitution is essential in the treatment of urea cycle defects as creatine is inefficiently transported into the brain

The in-plane electrodynamics of the superconductivity in Bi2Sr2CaCu2O8+d: energy scales and spectral weight distribution

The in-plane infrared and visible (3 meV-3 eV) reflectivity of Bi2Sr2CaCu2O8+d (Bi-2212) thin films is measured between 300 K and 10 K for different doping levels with unprecedented accuracy. The optical conductivity is derived through an accurate fitting procedure. We study the transfer of spectral weight from finite energy into the superfluid as the system becomes superconducting. In the over-doped regime, the superfluid develops at the expense of states lying below 60 meV, a conventional energy of the order of a few times the superconducting gap. In the underdoped regime, spectral weight is removed from up to 2 eV, far beyond any conventional scale. The intraband spectral weight change between the normal and superconducting state, if analyzed in terms of a change of kinetic energy is ~1 meV. Compared to the condensation energy, this figure addresses the issue of a kinetic energy driven mechanism.Comment: 13 pages with 9 figures include

Radioactive decays at limits of nuclear stability

The last decades brought an impressive progress in synthesizing and studying properties of nuclides located very far from the beta stability line. Among the most fundamental properties of such exotic nuclides, usually established first, is the half-life, possible radioactive decay modes, and their relative probabilities. When approaching limits of nuclear stability, new decay modes set in. First, beta decays become accompanied by emission of nucleons from highly excited states of daughter nuclei. Second, when the nucleon separation energy becomes negative, nucleons start to be emitted from the ground state. Here, we present a review of the decay modes occurring close to the limits of stability. The experimental methods used to produce, identify and detect new species and their radiation are discussed. The current theoretical understanding of these decay processes is overviewed. The theoretical description of the most recently discovered and most complex radioactive process - the two-proton radioactivity - is discussed in more detail.Comment: Review, 68 pages, 39 figure

Integer Quantum Hall Effect in Graphite

We present Hall effect measurements on highly oriented pyrolytic graphite that indicate the occurrence of the integer quantum-Hall-effect. The evidence is given by the observation of regular plateau-like structures in the field dependence of the transverse conductivity obtained in van der Pauw configuration. Measurements with the Corbino-disk configuration support this result and indicate that the quasi-linear and non-saturating longitudinal magnetoresistance in graphite is governed by the Hall effect in agreement with a recent theoretical model for disordered semiconductors.Comment: 3 figures, to be published in Solid State Communication (2006

Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome

Background The introduction of molecular karyotyping technologies facilitated the identification of specific genetic disorders associated with imbalances of certain genomic regions. A detailed phenotypic delineation of interstitial 16p13.3 duplications is hampered by the scarcity of such patients. Objectives To delineate the phenotypic spectrum associated with interstitial 16p13.3 duplications, and perform a genotype-phenotype analysis. Results The present report describes the genotypic and phenotypic delineation of nine submicroscopic interstitial 16p13.3 duplications. The critically duplicated region encompasses a single gene, CREBBP, which is mutated or deleted in Rubinstein-Taybi syndrome. In 10 out of the 12 hitherto described probands, the duplication arose de novo. Conclusions Interstitial 16p13.3 duplications have a recognizable phenotype, characterized by normal to moderately retarded mental development, normal growth, mild arthrogryposis, frequently small and proximally implanted thumbs and characteristic facial features. Occasionally, developmental defects of the heart, genitalia, palate or the eyes are observed. The frequent de novo occurrence of 16p13.3 duplications demonstrates the reduced reproductive fitness associated with this genotype. Inheritance of the duplication from a clinically normal parent in two cases indicates that the associated phenotype is incompletely penetrant

Virtual reality, ultrasound-guided liver biopsy simulator: Development and performance discrimination

Objectives: The aim of this article was to identify and prospectively investigate simulated ultrasound-guided targeted liver biopsy performance metrics as differentiators between levels of expertise in interventional radiology. Methods: Task analysis produced detailed procedural step documentation allowing identification of critical procedure steps and performance metrics for use in a virtual reality ultrasound-guided targeted liver biopsy procedure. Consultant (n=14; male=11, female=3) and trainee (n=26; male=19, female=7) scores on the performance metrics were compared. Ethical approval was granted by the Liverpool Research Ethics Committee (UK). Independent t-tests and analysis of variance (ANOVA) investigated differences between groups. Results: Independent t-tests revealed significant differences between trainees and consultants on three performance metrics: targeting, p=0.018, t=22.487 (22.040 to 20.207); probe usage time, p=0.040, t=2.132 (11.064 to 427.983); mean needle length in beam, p=0.029, t=22.272 (20.028 to 20.002). ANOVA reported significant differences across years of experience (0–1, 1–2, 3+ years) on seven performance metrics: no-go area touched, p=0.012; targeting, p=0.025; length of session, p=0.024; probe usage time, p=0.025; total needle distance moved, p=0.038; number of skin contacts, p<0.001; total time in no-go area, p=0.008. More experienced participants consistently received better performance scores on all 19 performance metrics. Conclusion: It is possible to measure and monitor performance using simulation, with performance metrics providing feedback on skill level and differentiating levels of expertise. However, a transfer of training study is required

Combined potential and spin impurity scattering in cuprates

We present a theory of combined nonmagnetic and magnetic impurity scattering in anisotropic superconductors accounting for the momentum-dependent impurity potential. Applying the model to the d-wave superconducting state, we obtain a quantitative agreement with the initial suppression of the critical temperature due to Zn and Ni substitutions as well as electron irradiation defects in the cuprates. We suggest, that the unequal pair-breaking effect of Zn and Ni may be related to a different nature of the magnetic moments induced by these impurities.Comment: 5 pages, 3 tables, RevTex, to be published in Phys. Rev.

Structural insights into ring-building motif domains involved in bacterial sporulation.

Components of specialized secretion systems, which span the inner and outer membranes in Gram-negative bacteria, include ring-forming proteins whose oligomerization was proposed to be promoted by domains called RBM for "Ring-Building Motifs". During spore formation in Gram-positive bacteria, a transport system called the SpoIIIA-SpoIIQ complex also assembles in the double membrane that surrounds the forespore following its endocytosis by the mother cell. The presence of RBM domains in some of the SpoIIIA proteins led to the hypothesis that they would assemble into rings connecting the two membranes and form a conduit between the mother cell and forespore. Among them, SpoIIIAG forms homo-oligomeric rings in vitro but the oligomerization of other RBM-containing SpoIIIA proteins, including SpoIIIAH, remains to be demonstrated. In this work, we identified RBM domains in the YhcN/YlaJ family of proteins that are not related to the SpoIIIA-SpoIIQ complex. We solved the crystal structure of YhcN from Bacillus subtilis, which confirmed the presence of a RBM fold, flanked by additional secondary structures. As the protein did not show any oligomerization ability in vitro, we investigated the structural determinants of ring formation in SpoIIIAG, SpoIIIAH and YhcN. We showed that in vitro, the conserved core of RBM domains alone is not sufficient for oligomerization while the β-barrel forming region in SpoIIIAG forms rings on its own. This work suggests that some RBMs might indeed participate in the assembly of homomeric rings but others might have evolved toward other functions

The Explosion in Orion-KL as Seen by Mosaicking the Magnetic Field with ALMA

We present the first linear-polarization mosaicked observations performed by the Atacama Large Millimeter/submillimeter Array (ALMA). We mapped the Orion-KLeinmann-Low (Orion-KL) nebula using super-sampled mosaics at 3.1 and 1.3 mm as part of the ALMA Extension and Optimization of Capabilities (EOC) program. We derive the magnetic field morphology in the plane of the sky by assuming that dust grains are aligned with respect to the ambient magnetic field. At the center of the nebula, we find a quasi-radial magnetic field pattern that is aligned with the explosive CO outflow up to a radius of approximately 12 arc-seconds (~ 5000 au), beyond which the pattern smoothly transitions into a quasi-hourglass shape resembling the morphology seen in larger-scale observations by the James-Clerk-Maxwell Telescope (JCMT). We estimate an average magnetic field strength $\langle B\rangle = 9.4$ mG and a total magnetic energy of 2 x 10^45 ergs, which is three orders of magnitude less than the energy in the explosive CO outflow. We conclude that the field has been overwhelmed by the outflow and that a shock is propagating from the center of the nebula, where the shock front is seen in the magnetic field lines at a distance of ~ 5000 au from the explosion center.Comment: Accepted for publication in Ap

The ALMA Frontier Fields Survey

CONTEXT: Dusty star-forming galaxies are among the most prodigious systems at high redshift (z > 1), characterized by high star-formation rates and huge dust reservoirs. The bright end of this population has been well characterized in recent years, but considerable uncertainties remain for fainter dusty star-forming galaxies, which are responsible for the bulk of star formation at high redshift and thus play a key role in galaxy growth and evolution. AIMS: In this first paper of our series, we describe our methods for finding high redshift faint dusty galaxies using millimeter observations with ALMA. METHODS: We obtained ALMA 1.1 mm mosaic images for three strong-lensing galaxy clusters from the Frontier Fields Survey, which constitute some of the best studied gravitational lenses to date. The ≈2′ × 2′ mosaics overlap with the deep HST WFC3/IR footprints and encompass the high magnification regions of each cluster for maximum intrinsic source sensitivity. The combination of extremely high ALMA sensitivity and the magnification power of these clusters allows us to systematically probe the sub-mJy population of dusty star-forming galaxies over a large surveyed area. RESULTS: We present a description of the reduction and analysis of the ALMA continuum observations for the galaxy clusters Abell 2744 (z = 0.308), MACS J0416.1-2403 (z = 0.396) and MACS J1149.5+2223 (z = 0.543), for which we reach observed rms sensitivities of 55, 59 and 71 μJy beam-1 respectively. We detect 12 dusty star-forming galaxies at S/N ≥ 5.0 across the three clusters, all of them presenting coincidence with near-infrared detected counterparts in the HST images. None of the sources fall close to the lensing caustics, thus they are not strongly lensed. The observed 1.1 mm flux densities for the total sample of galaxies range from 0.41 to 2.82 mJy, with observed effective radii spanning ≲0.̋05 to 0.̋37 ± 0.̋21 . The lensing-corrected sizes of the detected sources appear to be in the same range as those measured in brighter samples, albeit with possibly larger dispersion