High-Throughput SNP Genotyping by SBE/SBH

Despite much progress over the past decade, current Single Nucleotide Polymorphism (SNP) genotyping technologies still offer an insufficient degree of multiplexing when required to handle user-selected sets of SNPs. In this paper we propose a new genotyping assay architecture combining multiplexed solution-phase single-base extension (SBE) reactions with sequencing by hybridization (SBH) using universal DNA arrays such as all $k$-mer arrays. In addition to PCR amplification of genomic DNA, SNP genotyping using SBE/SBH assays involves the following steps: (1) Synthesizing primers complementing the genomic sequence immediately preceding SNPs of interest; (2) Hybridizing these primers with the genomic DNA; (3) Extending each primer by a single base using polymerase enzyme and dideoxynucleotides labeled with 4 different fluorescent dyes; and finally (4) Hybridizing extended primers to a universal DNA array and determining the identity of the bases that extend each primer by hybridization pattern analysis. Our contributions include a study of multiplexing algorithms for SBE/SBH genotyping assays and preliminary experimental results showing the achievable tradeoffs between the number of array probes and primer length on one hand and the number of SNPs that can be assayed simultaneously on the other. Simulation results on datasets both randomly generated and extracted from the NCBI dbSNP database suggest that the SBE/SBH architecture provides a flexible and cost-effective alternative to genotyping assays currently used in the industry, enabling genotyping of up to hundreds of thousands of user-specified SNPs per assay.Comment: 19 page

COrE (Cosmic Origins Explorer) A White Paper

COrE (Cosmic Origins Explorer) is a fourth-generation full-sky, microwave-band satellite recently proposed to ESA within Cosmic Vision 2015-2025. COrE will provide maps of the microwave sky in polarization and temperature in 15 frequency bands, ranging from 45 GHz to 795 GHz, with an angular resolution ranging from 23 arcmin (45 GHz) and 1.3 arcmin (795 GHz) and sensitivities roughly 10 to 30 times better than PLANCK (depending on the frequency channel). The COrE mission will lead to breakthrough science in a wide range of areas, ranging from primordial cosmology to galactic and extragalactic science. COrE is designed to detect the primordial gravitational waves generated during the epoch of cosmic inflation at more than $3\sigma$ for $r=(T/S)>=10^{-3}$. It will also measure the CMB gravitational lensing deflection power spectrum to the cosmic variance limit on all linear scales, allowing us to probe absolute neutrino masses better than laboratory experiments and down to plausible values suggested by the neutrino oscillation data. COrE will also search for primordial non-Gaussianity with significant improvements over Planck in its ability to constrain the shape (and amplitude) of non-Gaussianity. In the areas of galactic and extragalactic science, in its highest frequency channels COrE will provide maps of the galactic polarized dust emission allowing us to map the galactic magnetic field in areas of diffuse emission not otherwise accessible to probe the initial conditions for star formation. COrE will also map the galactic synchrotron emission thirty times better than PLANCK. This White Paper reviews the COrE science program, our simulations on foreground subtraction, and the proposed instrumental configuration.Comment: 90 pages Latex 15 figures (revised 28 April 2011, references added, minor errors corrected

Combinatorics and Geometry of Transportation Polytopes: An Update

A transportation polytope consists of all multidimensional arrays or tables of non-negative real numbers that satisfy certain sum conditions on subsets of the entries. They arise naturally in optimization and statistics, and also have interest for discrete mathematics because permutation matrices, latin squares, and magic squares appear naturally as lattice points of these polytopes. In this paper we survey advances on the understanding of the combinatorics and geometry of these polyhedra and include some recent unpublished results on the diameter of graphs of these polytopes. In particular, this is a thirty-year update on the status of a list of open questions last visited in the 1984 book by Yemelichev, Kovalev and Kravtsov and the 1986 survey paper of Vlach.Comment: 35 pages, 13 figure

Inflation and the Scale Dependent Spectral Index: Prospects and Strategies

We consider the running of the spectral index as a probe of both inflation itself, and of the overall evolution of the very early universe. Surveying a collection of simple single field inflationary models, we confirm that the magnitude of the running is relatively consistent, unlike the tensor amplitude, which varies by orders of magnitude. Given this target, we confirm that the running is potentially detectable by future large scale structure or 21 cm observations, but that only the most futuristic measurements can distinguish between these models on the basis of their running. For any specified inflationary scenario, the combination of the running index and unknown post-inflationary expansion history induces a theoretical uncertainty in the predicted value of the spectral index. This effect can easily dominate the statistical uncertainty with which Planck and its successors are expected to measure the spectral index. More positively, upcoming cosmological experiments thus provide an intriguing probe of physics between TeV and GUT scales by constraining the reheating history associated with any specified inflationary model, opening a window into the "primordial dark age" that follows the end of inflation.Comment: 32 pages. v2 and v3 Minor reference updates /clarification

Delay Differential Analysis of Seizures in Multichannel Electrocorticography Data

High-density electrocorticogram (ECoG) electrodes are capable of recording neurophysiological data with high temporal resolution with wide spatial coverage. These recordings are a window to understanding how the human brain processes information and subsequently behaves in healthy and pathologic states. Here, we describe and implement delay differential analysis (DDA) for the characterization of ECoG data obtained from human patients with intractable epilepsy. DDA is a time-domain analysis framework based on embedding theory in nonlinear dynamics that reveals the nonlinear invariant properties of an unknown dynamical system. The DDA embedding serves as a low-dimensional nonlinear dynamical basis onto which the data are mapped. This greatly reduces the risk of overfitting and improves the method's ability to fit classes of data. Since the basis is built on the dynamical structure of the data, preprocessing of the data (e.g., filtering) is not necessary. We performed a large-scale search for a DDA model that best fit ECoG recordings using a genetic algorithm to qualitatively discriminate between different cortical states and epileptic events for a set of 13 patients. A single DDA model with only three polynomial terms was identified. Singular value decomposition across the feature space of the model revealed both global and local dynamics that could differentiate electrographic and electroclinical seizures and provided insights into highly localized seizure onsets and diffuse seizure terminations. Other common ECoG features such as interictal periods, artifacts, and exogenous stimuli were also analyzed with DDA. This novel framework for signal processing of seizure information demonstrates an ability to reveal unique characteristics of the underlying dynamics of the seizure and may be useful in better understanding, detecting, and maybe even predicting seizures

Supersymmetry at the Tevatron ?

These lectures contain an introduction to the search for supersymmetry at hadron colliders. The Tevatron is one of high-energy physics most sophisticated tools. The high center-of-mass energy of its proton-antiproton collisions makes it an ideal place to search for physics beyond the Standard Model, such as supersymmetry. Two experiments, CDF and D\O, completed a long data taking period in summer of 1995, yielding over $100 p b^{-1}$ of proton-- antiproton interactions. The data recorded by the experiments are still being analysed. The lectures outline the strategies in the search for supersymmetry at the Tevatron and examine the major analyses in detail. Results obtained by the two experiments are included where available.Comment: 40 pages, 13 figure

CMB-S4 Science Book, First Edition

This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales

Parton theory of magnetic polarons: Mesonic resonances and signatures in dynamics

When a mobile hole is moving in an anti-ferromagnet it distorts the surrounding Neel order and forms a magnetic polaron. Such interplay between hole motion and anti-ferromagnetism is believed to be at the heart of high-Tc superconductivity in cuprates. We study a single hole described by the t-Jz model with Ising interactions between the spins in 2D. This situation can be experimentally realized in quantum gas microscopes. When the hole hopping is much larger than couplings between the spins, we find strong evidence that magnetic polarons can be understood as bound states of two partons, a spinon and a holon carrying spin and charge quantum numbers respectively. We introduce a microscopic parton description which is benchmarked by comparison with results from advanced numerical simulations. Using this parton theory, we predict a series of excited states that are invisible in the spectral function and correspond to rotational excitations of the spinon-holon pair. This is reminiscent of mesonic resonances observed in high-energy physics, which can be understood as rotating quark antiquark pairs. We also apply the strong coupling parton theory to study far-from equilibrium dynamics of magnetic polarons observable in current experiments with ultracold atoms. Our work supports earlier ideas that partons in a confining phase of matter represent a useful paradigm in condensed-matter physics and in the context of high-Tc superconductivity. While direct observations of spinons and holons in real space are impossible in traditional solid-state experiments, quantum gas microscopes provide a new experimental toolbox. We show that, using this platform, direct observations of partons in and out-of equilibrium are possible. Extensions of our approach to the t-J model are also discussed. Our predictions in this case are relevant to current experiments with quantum gas microscopes for ultracold atoms.Comment: 30 pages, 4 appendices, 26 figure