Autoantibodies against the N-Methyl-D-Aspartate receptor subunit NR1: Untangling apparent inconsistencies for clinical practice

This viewpoint review provides an integrative picture of seemingly contradictory work published on N-methyl-d-aspartate receptor 1 (NMDAR1) autoantibodies (AB). Based on the present state of knowledge, it gives recommendations for the clinical decision process regarding immunosuppressive treatment. Brain antigen-directed AB in general and NMDAR1-AB in particular belong to a preexisting autoimmune repertoire of mammals including humans. Specific autoimmune reactive B cells may get repeatedly (perhaps transiently) boosted by various potential stimulants (e.g., microbiome, infections, or neoplasms) plus less efficiently suppressed over lifespan (gradual loss of tolerance), likely explaining the increasing seroprevalence upon aging (>20% NMDAR1-AB in 80-year-old humans). Pathophysiological significance emerges (I) when AB-specific plasma cells settle in the brain and produce large amounts of brain antigen-directed AB intrathecally and/or (II) in conditions of compromised blood–brain barrier (BBB), for instance, upon injury, infection, inflammation, or genetic predisposition (APOE4 haplotype), which then allows substantial access of circulating AB to the brain. Regarding NMDAR1-AB, functional effects on neurons in vitro and elicitation of brain symptoms in vivo have been demonstrated for immunoglobulin (Ig) classes, IgM, IgA, and IgG. Under conditions of brain inflammation, intrathecal production and class switch to IgG may provoke high NMDAR1-AB (and other brain antigen-directed AB) levels in cerebrospinal fluid (CSF) and serum, causing the severe syndrome named “anti-NMDAR encephalitis,” which then requires immunosuppressive therapy on top of the causal encephalitis treatment (if available). However, negative CSF NMDAR1-AB results cannot exclude chronic effects of serum NMDAR1-AB on the central nervous system, since the brain acts as “immunoprecipitator,” particularly in situations of compromised BBB. In any case of suspected symptomatic consequences of circulating AB directed against brain antigens, leakiness of the BBB should be evaluated by CSF analysis (albumin quotient as proxy) and magnetic resonance imaging before considering immunosuppression

Phonon Dispersion Effects and the Thermal Conductivity Reduction in GaAs/AlAs Superlattices

The experimentally observed order-of-magnitude reduction in the thermal conductivity along the growth axis of (GaAs)_n/(AlAs)_n (or n x n) superlattices is investigated theoretically for (2x2), (3x3) and (6x6) structures using an accurate model of the lattice dynamics. The modification of the phonon dispersion relation due to the superlattice geometry leads to flattening of the phonon branches and hence to lower phonon velocities. This effect is shown to account for a factor-of-three reduction in the thermal conductivity with respect to bulk GaAs along the growth direction; the remainder is attributable to a reduction in the phonon lifetime. The dispersion-related reduction is relatively insensitive to temperature (100 < T < 300K) and n. The phonon lifetime reduction is largest for the (2x2) structures and consistent with greater interface scattering. The thermal conductivity reduction is shown to be appreciably more sensitive to GaAs/AlAs force constant differences than to those associated with molecular masses.Comment: 5 figure

Phenotype-based genetic association studies (PGAS) - towards understanding the contribution of common genetic variants to schizophrenia subphenotypes

Neuropsychiatric diseases ranging from schizophrenia to affective disorders and autism are heritable, highly complex and heterogeneous conditions, diagnosed purely clinically, with no supporting biomarkers or neuroimaging criteria. Relying on these “umbrella diagnoses”, genetic analyses, including genome-wide association studies (GWAS), were undertaken but failed to provide insight into the biological basis of these disorders. “Risk genotypes” of unknown significance with low odds ratios of mostly &lt;1.2 were extracted and confirmed by including ever increasing numbers of individuals in large multicenter efforts. Facing these results, we have to hypothesize that thousands of genetic constellations in highly variable combinations with environmental co-factors can cause the individual disorder in the sense of a final common pathway. This would explain why the prevalence of mental diseases is so high and why mutations, including copy number variations, with a higher effect size than SNPs, constitute only a small part of variance. Elucidating the contribution of normal genetic variation to (disease) phenotypes, and so re-defining disease entities, will be extremely labor-intense but crucial. We have termed this approach PGAS (“phenotype-based genetic association studies”). Ultimate goal is the definition of biological subgroups of mental diseases. For that purpose, the GRAS (Göttingen Research Association for Schizophrenia) data collection was initiated in 2005. With &gt;3000 phenotypical data points per patient, it comprises the world-wide largest currently available schizophrenia database (N &gt; 1200), combining genome-wide SNP coverage and deep phenotyping under highly standardized conditions. First PGAS results on normal genetic variants, relevant for e.g., cognition or catatonia, demonstrated proof-of-concept. Presently, an autistic subphenotype of schizophrenia is being defined where an unfortunate accumulation of normal genotypes, so-called pro-autistic variants of synaptic genes, explains part of the phenotypical variance. Deep phenotyping and comprehensive clinical data sets, however, are expensive and it may take years before PGAS will complement conventional GWAS approaches in psychiatric genetics

Coherent Exciton Lasing in ZnSe/ZnCdSe Quantum Wells?

A new mechanism for exciton lasing in ZnSe/ZnCdSe quantum wells is proposed. Lasing, occurring below the lowest exciton line, may be associated with a BCS-like condensed (coherent) exciton state. This state is most stable at low temperatures for densities in the transition region separating the exciton Bose gas and the coherent exciton state. Calculations show the gain region to lie below the exciton line and to be separated from the absorption regime by a transparency region of width, for example, about 80 meV for a 90 Angstrom ZnSe/Zn_(0.75)Cd_(0.25)Se quantum well. Experimental observation of the transparency region using differential spectroscopy would confirm this picture.Comment: 9 pages + 3 figs contained in 4 postscript files to appear Appl. Phys. Lett. March 13, 199

Microscopic gauge-invariant theory of the c-axis infrared response of bilayer cuprate superconductors and the origin of the superconductivity induced absorption bands

We report on results of our theoretical study of the c-axis infrared conductivity of bilayer high-Tc cuprate superconductors using a microscopic model involving the bilayer-split (bonding and antibonding) bands. An emphasis is on the gauge-invariance of the theory, which turns out to be essential for the physical understanding of the electrodynamics of these compounds. The description of the optical response involves local (intra-bilayer and inter-bilayer) current densities and local conductivities. The local conductivities are obtained using a microscopic theory, where the quasiparticles of the two bands are coupled to spin fluctuations. The coupling leads to superconductivity and is described at the level of generalized Eliashberg theory. Also addressed is the simpler case of quasiparticles coupled by a separable and nonretarded interaction. The gauge invariance of the theory is achieved by including a suitable class of vertex corrections. The resulting response of the model is studied in detail and an interpretation of two superconductivity-induced peaks in the experimental data of the real part of the c-axis conductivity is proposed. The peak around 400/cm is attributed to a collective mode of the intra-bilayer regions, that is an analogue of the Bogolyubov-Anderson mode playing a crucial role in the theory of the longitudinal response of superconductors. For small values of the bilayer splitting, its nature is similar to that of the transverse plasmon of the phenomenological Josephson superlattice model. The peak around 1000/cm is interpreted as a pair breaking-feature that is related to the electronic coupling through the spacing layers separating the bilayers.Comment: 18 pages, 15 figures, submitted to Phys. Rev.

Soccer, neurotrauma and amyotrophic lateral sclerosis: is there a connection?

Curr Med Res Opin. 2004 Apr;20(4):505-8

Sparse aperture masking at the VLT II. Detection limits for the eight debris disks stars β\beta Pic, AU Mic, 49 Cet, η\eta Tel, Fomalhaut, g Lup, HD181327 and HR8799

Context. The formation of planetary systems is a common, yet complex mechanism. Numerous stars have been identified to possess a debris disk, a proto-planetary disk or a planetary system. The understanding of such formation process requires the study of debris disks. These targets are substantial and particularly suitable for optical and infrared observations. Sparse Aperture masking (SAM) is a high angular resolution technique strongly contributing to probe the region from 30 to 200 mas around the stars. This area is usually unreachable with classical imaging, and the technique also remains highly competitive compared to vortex coronagraphy. Aims. We aim to study debris disks with aperture masking to probe the close environment of the stars. Our goal is either to find low mass companions, or to set detection limits. Methods. We observed eight stars presenting debris disks ( $\beta$ Pictoris, AU Microscopii, 49 Ceti, $\eta$ Telescopii, Fomalhaut, g Lupi, HD181327 and HR8799) with SAM technique on the NaCo instrument at the VLT. Results. No close companions were detected using closure phase information under 0.5 of separation from the parent stars. We obtained magnitude detection limits that we converted to Jupiter masses detection limits using theoretical isochrones from evolutionary models. Conclusions. We derived upper mass limits on the presence of companions in the area of few times the diffraction limit of the telescope around each target star.Comment: 7 pages, All magnitude detection limits maps are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5

Tuning Fermi-surface properties through quantum confinement in metallic meta-lattices: New metals from old atoms

We describe a new class of nanoscale structured metals wherein the effects of quantum confinement are combined with dispersive metallic electronic states to induce modifications to the fundamental low-energy microscopic properties of a three-dimensional metal: the density of states, the distribution of Fermi velocities, and the collective electronic response.Comment: 4 pages, 5 figures, to appear in Phys. Rev. Let

High resolution imaging of young M-type stars of the solar neighborhood: Probing the existence of companions down to the mass of Jupiter

Context. High contrast imaging is a powerful technique to search for gas giant planets and brown dwarfs orbiting at separation larger than several AU. Around solar-type stars, giant planets are expected to form by core accretion or by gravitational instability, but since core accretion is increasingly difficult as the primary star becomes lighter, gravitational instability would be the a probable formation scenario for yet-to-be-found distant giant planets around a low-mass star. A systematic survey for such planets around M dwarfs would therefore provide a direct test of the efficiency of gravitational instability. Aims. We search for gas giant planets orbiting around late-type stars and brown dwarfs of the solar neighborhood. Methods. We obtained deep high resolution images of 16 targets with the adaptive optic system of VLT-NACO in the Lp band, using direct imaging and angular differential imaging. This is currently the largest and deepest survey for Jupiter-mass planets around Mdwarfs. We developed and used an integrated reduction and analysis pipeline to reduce the images and derive our 2D detection limits for each target. The typical contrast achieved is about 9 magnitudes at 0.5" and 11 magnitudes beyond 1". For each target we also determine the probability of detecting a planet of a given mass at a given separation in our images. Results. We derived accurate detection probabilities for planetary companions, taking into account orbital projection effects, with in average more than 50% probability to detect a 3MJup companion at 10AU and a 1.5MJup companion at 20AU, bringing strong constraints on the existence of Jupiter-mass planets around this sample of young M-dwarfs.Comment: Accepted for publication in A&