Damped Lyman alpha absorber and the faint end of the galaxy luminosity function at high redshift

We combine predictions for several hierarchical cosmogonies with observational evidence on damped Lyman alpha systems to establish a correspondence between the high redshift galaxy population and the properties of damped Lyman alpha systems. We assume that high redshift galaxies and damped Lyman alpha systems are hosted by the same dark matter halos and require consistency between the predicted halo space density, the rate of incidence and the velocity width distribution of damped Lyman alpha systems, and the observed galaxy luminosity function at the bright end. We arrive at the following results: (1) predicted impact parameters between the damped absorption system and the luminous part of the absorbing galaxy are expected to be very small (0.3 - 1arcsec) for most galaxies; (2) luminosities of galaxies causing damped absorption are generally fainter than m_R = 25 and damped Lyman alpha systems are predicted to sample preferentially the outer regions of galaxies at the faint end of the galaxy luminosity function at high redshift. Therefore, DLAS should currently provide the best probe of the progenitors of normal present-day galaxies.Comment: 4 pages, LaTeX, emulateapj, 4 postscript figures included, submitted to Ap

CIV Absorption From Galaxies in the Process of Formation

We investigate the heavy element QSO absorption systems caused by gas condensations at high redshift which evolve into galaxies with circular velocity of 100 to 200 km/s at the present epoch. Artificial QSO spectra were generated for a variety of lines-of-sight through regions of the universe simulated with a hydrodynamics code. The CIV and HI absorption features in these spectra closely resemble observed CIV and HI absorption systems over a wide range in column density. CIV absorption complexes with multiple-component structure and velocity spreads up to about 600 km/s are found. The broadest systems are caused by lines-of-sight passing through groups of protogalactic clumps with individual velocity dispersions of less than 150 km/s aligned along filamentary structures. The temperature of most of the gas does not take the photoionization equilibrium value. This invalidates density and size estimates derived from thermal equilibrium models. Consequences for metal abundance determinations are briefly discussed. We predict occasional exceptionally large ratios of CIV to HI column density (up to a third) for lines-of-sight passing through compact halos of hot gas with temperature close to 3 10^5 K. Our model may be able to explain both high-ionization multi-component heavy-element absorbers and damped Lyman alpha systems as groups of small protogalactic clumps.Comment: 13 pages, uuencoded postscript file, 4 figures included submitted to ApJ (Letters); complete version also available at http://www.mpa-garching.mpg.de/Galaxien/prep.htm

γ Heavy Chain Disease in Man: cDNA Sequence Supports Partial Gene Deletion Model

Human gamma heavy chain disease (HCD) is characterized by the presence in serum of a short monoclonal Ig gamma chain unattached to light chains. Although most HCD proteins have internal deletions, in some the defect is NH2-terminal. The OMM gamma 3 HCD serum protein is of the latter type, having undergone an extensive NH2-terminal deletion with a sequence starting within the hinge. A cell line synthesizing the OMM protein has enabled us to study the biogenesis of the abnormal molecule. In vitro translation of isolated mRNA yields a protein containing a hydrophobic NH2-terminal leader sequence. In the intact cell, the precursor molecule is processed normally to yield a protein with an NH2-terminal sequence homologous to the beginning of the variable (V) region. The nucleotide sequence of cDNA prepared from the OMM mRNA encodes a 19-amino acid leader followed by the first 15 residues of the V region. An extensive internal deletion encompasses the remainder of the V and the entire CHl domain. Immediately following the short V region, there is information in the cDNA for the entire normal hinge. The primary synthetic product is thus an internally deleted molecule that undergoes postsynthetic degradation to yield the NH2-terminally deleted serum protein. The structure of the OMM mRNA suggests that the protein abnormality results from a partial gene deletion rather than defective splicing

Subthreshold Voltage Noise Due to Channel Fluctuations in Active Neuronal Membranes

Voltage-gated ion channels in neuronal membranes fluctuate randomly between different conformational states due to thermal agitation. Fluctuations between conducting and nonconducting states give rise to noisy membrane currents and subthreshold voltage fluctuations and may contribute to variability in spike timing. Here we study subthreshold voltage fluctuations due to active voltage-gated Na+ and K+ channels as predicted by two commonly used kinetic schemes: the Mainen et al. (1995) (MJHS) kinetic scheme, which has been used to model dendritic channels in cortical neurons, and the classical Hodgkin-Huxley (1952) (HH) kinetic scheme for the squid giant axon. We compute the magnitudes, amplitude distributions, and power spectral densities of the voltage noise in isopotential membrane patches predicted by these kinetic schemes. For both schemes, noise magnitudes increase rapidly with depolarization from rest. Noise is larger for smaller patch areas but is smaller for increased model temperatures. We contrast the results from Monte Carlo simulations of the stochastic nonlinear kinetic schemes with analytical, closed-form expressions derived using passive and quasi-active linear approximations to the kinetic schemes. For all subthreshold voltage ranges, the quasi-active linearized approximation is accurate within 8% and may thus be used in large-scale simulations of realistic neuronal geometries

Targeted disruption of the MHC class II Aa gene in C57BL/6 mice

The MHC class II gene Aa was disrupted by targeted mutation in embryonic stem (ES) cells derived from C57BL/6 mice to prevent expression of MHC class II molecules. Contrary to previous reports, the effect of the null-mutation on T cell development was investigated in C57BL/6 mice, which provide a defined genetic background. The complete lack of cell surface expression of MHC class II molecules in B6-Aa0/Aa0 homozygous mutant mice was directly demonstrated by cytofiuorometric analysis using anti-Ab and anti-la specific mAbs. Development of CD4+CD8− T cells in the thymus was largely absent except for a small population of thymocytes expressing high levels of CD4 together with low amounts of CD8. The majority of these cells express the TCR at high density. Although mature CD4+CD8− T cells were undetectable in the thymus, some T cells with a CD4+CD8−TCRhigh phenotype were found in lymph nodes and spleen. Peripheral T cells from themutant mice can be polyclonally activated in vitro with the mitogen concanavalin A. However, they could not be stimulated with staphylococcal enterotoxin B in autologous lymphocyte reactions, thereby demonstrating the absence of MHC class II expression in these mice. Peripheral B cells in B6-Aa0/Aa0 mutants were functional and responded to the T cell independent antigen levan by the production of antigenspecific IgM antibodies similar to wild-type cells. The B6-Aa0/Aa0 mutant mice described in this study represent an important tool to investigate the involvement of MHC class II molecules in lymphocyte maturation and the immune respons

MAG: A Multilingual, Knowledge-base Agnostic and Deterministic Entity Linking Approach

Entity linking has recently been the subject of a significant body of research. Currently, the best performing approaches rely on trained mono-lingual models. Porting these approaches to other languages is consequently a difficult endeavor as it requires corresponding training data and retraining of the models. We address this drawback by presenting a novel multilingual, knowledge-based agnostic and deterministic approach to entity linking, dubbed MAG. MAG is based on a combination of context-based retrieval on structured knowledge bases and graph algorithms. We evaluate MAG on 23 data sets and in 7 languages. Our results show that the best approach trained on English datasets (PBOH) achieves a micro F-measure that is up to 4 times worse on datasets in other languages. MAG, on the other hand, achieves state-of-the-art performance on English datasets and reaches a micro F-measure that is up to 0.6 higher than that of PBOH on non-English languages.Comment: Accepted in K-CAP 2017: Knowledge Capture Conferenc

Length, Protein-Protein Interactions, and Complexity

The evolutionary reason for the increase in gene length from archaea to prokaryotes to eukaryotes observed in large scale genome sequencing efforts has been unclear. We propose here that the increasing complexity of protein-protein interactions has driven the selection of longer proteins, as longer proteins are more able to distinguish among a larger number of distinct interactions due to their greater average surface area. Annotated protein sequences available from the SWISS-PROT database were analyzed for thirteen eukaryotes, eight bacteria, and two archaea species. The number of subcellular locations to which each protein is associated is used as a measure of the number of interactions to which a protein participates. Two databases of yeast protein-protein interactions were used as another measure of the number of interactions to which each \emph{S. cerevisiae} protein participates. Protein length is shown to correlate with both number of subcellular locations to which a protein is associated and number of interactions as measured by yeast two-hybrid experiments. Protein length is also shown to correlate with the probability that the protein is encoded by an essential gene. Interestingly, average protein length and number of subcellular locations are not significantly different between all human proteins and protein targets of known, marketed drugs. Increased protein length appears to be a significant mechanism by which the increasing complexity of protein-protein interaction networks is accommodated within the natural evolution of species. Consideration of protein length may be a valuable tool in drug design, one that predicts different strategies for inhibiting interactions in aberrant and normal pathways.Comment: 13 pages, 5 figures, 2 tables, to appear in Physica

Functional expression of a human TCRβ gene in transgenic mice

A functionally rearranged TCRβ (Tcrb) gene was isolated from a cloned human T helper cell recognizing the CS.T3 epitope of Plasmodium falciparum with HLA-DR2. Transgenic mice were generated by co-injection of the human gene together with the mouse Tcrb enhancer. Analysis of transgenic mice shows that the functional Tcrb gene of xenogenic, i.e. human, origin exerts allelic exclusion of endogenous Tcrb genes. Cytofluorometric analysis revealed expression of the human TCRβ chain on virtually all thymocytes and peripheral T cells together with endogenous TCRβ chains and CD3 components. No surface expression of mouse TCRβ chain or rearrangement of endogenous Tcr genes was detectable. Expression of the hybrid receptor causes a reduction in the number of thymocytes and a bias for CD4+CD8− T cells in the thymus as compared with non-transgenic littermates. Peripheral transgenic T cells mount a normal prollferative response against allogenelc targets in mixed lymphocyte reactions. These results show that a hybrid mouse/human TCR is able to pass positive and negative selection in the thymus, and is functional in transgenic mic