Fluorescence in situ hybridization of YAC clones after Alu-PCR amplification

Alu-PCR protocols were optimized for the generation of human DNA probes from yeast strains containing yeast artificial chromosomes (YACs) with human inserts between 100 and 800 kb in size. The resulting DNA probes were used in chromosome in situ suppression (CISS) hybridization experiments. Strong fluorescent signals on both chromatids indicated the localization of specific YAC clones, while two clearly distinguishable signals were observed in ≥90% of diploid nuclei Signal intensities were generally comparable to those observed using chromosome-specific alphoid DNA probes. This approach will facilitate the rapid mapping of YAC clones and their use in chromosome analysis at all stages of the cell cycle

Momentum Analyticity and Finiteness of the 1-Loop Superstring Amplitude

The Type II Superstring amplitude to 1-loop order is given by an integral of $\vartheta$-functions over the moduli space of tori, which diverges for real momenta. We construct the analytic continuation which renders this amplitude well defined and finite, and we find the expected poles and cuts in the complex momentum plane.Comment: 10pp, /UCLA/93/TEP/

Dispersion Relations in String Theory

We analyze the analytic continuation of the formally divergent one-loop amplitude for scattering of the graviton multiplet in the Type II Superstring. In particular we obtain explicit double and single dispersion relations, formulas for all the successive branch cuts extending out to plus infinity, as well as for the decay rate of a massive string state of arbitrary mass 2N into two string states of lower mass. We compare our results with the box diagram in a superposition of $\phi^3$-like field theories. The stringy effects are traced to a convergence problem in this superposition.Comment: 17 pages, COLUMBIA-YITP-UCLA/93/TEP/45 (figures fixed up

A common variant associated with dyslexia reduces expression of the KIAA0319 gene

This work was supported by the Wellcome Trust (MYD, SP, TSS, JCK, RWM, PC, SB, and APM), the Intramural Research Programs of the National Human Genome Research Institute (MYD and EDG) and National Cancer Institute (MPO), and the NIH/Ox-Cam Graduate Partnership Program (MYD).Numerous genetic association studies have implicated the KIAA0319 gene on human chromosome 6p22 in dyslexia susceptibility. The causative variant(s) remains unknown but may modulate gene expression, given that (1) a dyslexia-associated haplotype has been implicated in the reduced expression of KIAA0319, and (2) the strongest association has been found for the region spanning exon 1 of KIAA0319. Here, we test the hypothesis that variant(s) responsible for reduced KIAA0319 expression resides on the risk haplotype close to the gene's transcription start site. We identified seven single-nucleotide polymorphisms on the risk haplotype immediately upstream of KIAA0319 and determined that three of these are strongly associated with multiple reading-related traits. Using luciferase-expressing constructs containing the KIAA0319 upstream region, we characterized the minimal promoter and additional putative transcriptional regulator regions. This revealed that the minor allele of rs9461045, which shows the strongest association with dyslexia in our sample (max p-value = 0.0001), confers reduced luciferase expression in both neuronal and non-neuronal cell lines. Additionally, we found that the presence of this rs9461045 dyslexia-associated allele creates a nuclear protein-binding site, likely for the transcriptional silencer OCT-1. Knocking down OCT-1 expression in the neuronal cell line SHSY5Y using an siRNA restores KIAA0319 expression from the risk haplotype to nearly that seen from the non-risk haplotype. Our study thus pinpoints a common variant as altering the function of a dyslexia candidate gene and provides an illustrative example of the strategic approach needed to dissect the molecular basis of complex genetic traits.PostprintPeer reviewe

Metaphase and Interphase Cytogenetics with Alu-PCR-amplified Yeast Artificial Chromosome Clones Containing the BCR Gene and the Protooncogenes c-raf-1, c-fms, and c-erbB-21

A human yeast artificial chromosome (YAC) library was screened by polymerase chain reaction with oligonucleotide primers defined for DNA sequences of the BCR gene and the protooncogenes c-raf-1, c-fms, and c-erB-2. Alu-PCR-generated human DNA sequences were obtained from the respective YAC clones and used for fluorescence in situ hybridization experiments under suppression conditions. After chromosomal in situ suppression hybridization to GTG-banded human prometaphase chromosomes, seven of nine initially isolated YAC clones yielded strong signals exclusively in the chromosome bands containing the respective genes. Two clones yielded additional signals on other chromosomes and were excluded from further tests. The band-specific YACs were successfully applied to visualize specific structural chromosome aberrations in peripheral blood cells from patients with myelodysplasia exhibiting del(5)(q13q34), chronic myeloid leukemia and acute lymphocytic leukemia with t(9;22)(q34;q11), acute promyelocytic leukemia (M3) with t(15;17)(q22;q21), and in a cell line established from a proband with the constitutional translocation t(3;8)(p14.2;q24). In addition to the analysis of metaphase spreads, we demonstrate the particular usefulness of these YAC clones in combination with whole chromosome painting to analyze specific chromosome aberrations directly in the interphase nucleus

A point process framework for modeling electrical stimulation of the auditory nerve

Model-based studies of auditory nerve responses to electrical stimulation can provide insight into the functioning of cochlear implants. Ideally, these studies can identify limitations in sound processing strategies and lead to improved methods for providing sound information to cochlear implant users. To accomplish this, models must accurately describe auditory nerve spiking while avoiding excessive complexity that would preclude large-scale simulations of populations of auditory nerve fibers and obscure insight into the mechanisms that influence neural encoding of sound information. In this spirit, we develop a point process model of the auditory nerve that provides a compact and accurate description of neural responses to electric stimulation. Inspired by the framework of generalized linear models, the proposed model consists of a cascade of linear and nonlinear stages. We show how each of these stages can be associated with biophysical mechanisms and related to models of neuronal dynamics. Moreover, we derive a semi-analytical procedure that uniquely determines each parameter in the model on the basis of fundamental statistics from recordings of single fiber responses to electric stimulation, including threshold, relative spread, jitter, and chronaxie. The model also accounts for refractory and summation effects that influence the responses of auditory nerve fibers to high pulse rate stimulation. Throughout, we compare model predictions to published physiological data and explain differences in auditory nerve responses to high and low pulse rate stimulation. We close by performing an ideal observer analysis of simulated spike trains in response to sinusoidally amplitude modulated stimuli and find that carrier pulse rate does not affect modulation detection thresholds.Comment: 1 title page, 27 manuscript pages, 14 figures, 1 table, 1 appendi

System Modeling of Lunar Oxygen Production: Mass and Power Requirements

A systems analysis tool for estimating the mass and power requirements for a lunar oxygen production facility is introduced. The individual modeling components involve the chemical processing and cryogenic storage subsystems needed to process a beneficiated regolith stream into liquid oxygen via ilmenite reduction. The power can be supplied from one of six different fission reactor-converter systems. A baseline system analysis, capable of producing 15 metric tons of oxygen per annum, is presented. The influence of reactor-converter choice was seen to have a small but measurable impact on the system configuration and performance. Finally, the mission concept of operations can have a substantial impact upon individual component size and power requirements

Consistency Conditions for Orientifolds and D-Manifolds

We study superstrings with orientifold projections and with generalized open string boundary conditions (D-branes). We find two types of consistency condition, one related to the algebra of Chan-Paton factors and the other to cancellation of divergences. One consequence is that the Dirichlet 5-branes of the Type I theory carry a symplectic gauge group, as required by string duality. As another application we study the Type I theory on a $K3$ $Z_2$ orbifold, finding a family of consistent theories with various unitary and symplectic subgroups of $U(16) \times U(16)$. We argue that the $K3$ orbifold with spin connection embedded in gauge connection corresponds to an interacting conformal field theory in the Type I theory.Comment: Reference added. 27 pages LaTeX, 2 epsf figures. To appear in Phys.Rev.D (15Jly96