3,405 research outputs found
A genome-wide study of Hardy–Weinberg equilibrium with next generation sequence data
Statistical tests for Hardy–Weinberg equilibrium have been an important tool for detecting genotyping errors in the past, and remain important in the quality control of next generation sequence data. In this paper, we analyze complete chromosomes of the 1000 genomes project by using exact test procedures for autosomal and X-chromosomal variants. We find that the rate of disequilibrium largely exceeds what might be expected by chance alone for all chromosomes. Observed disequilibrium is, in about 60% of the cases, due to heterozygote excess. We suggest that most excess disequilibrium can be explained by sequencing problems, and hypothesize mechanisms that can explain exceptional heterozygosities. We report higher rates of disequilibrium for the MHC region on chromosome 6, regions flanking centromeres and p-arms of acrocentric chromosomes. We also detected long-range haplotypes and areas with incidental high disequilibrium. We report disequilibrium to be related to read depth, with variants having extreme read depths being more likely to be out of equilibrium. Disequilibrium rates were found to be 11 times higher in segmental duplications and simple tandem repeat regions. The variants with significant disequilibrium are seen to be concentrated in these areas. For next generation sequence data, Hardy–Weinberg disequilibrium seems to be a major indicator for copy number variation.Peer ReviewedPostprint (published version
Quantum resource estimates for computing elliptic curve discrete logarithms
We give precise quantum resource estimates for Shor's algorithm to compute
discrete logarithms on elliptic curves over prime fields. The estimates are
derived from a simulation of a Toffoli gate network for controlled elliptic
curve point addition, implemented within the framework of the quantum computing
software tool suite LIQ. We determine circuit implementations for
reversible modular arithmetic, including modular addition, multiplication and
inversion, as well as reversible elliptic curve point addition. We conclude
that elliptic curve discrete logarithms on an elliptic curve defined over an
-bit prime field can be computed on a quantum computer with at most qubits using a quantum circuit of at most Toffoli gates. We are able to classically simulate the
Toffoli networks corresponding to the controlled elliptic curve point addition
as the core piece of Shor's algorithm for the NIST standard curves P-192,
P-224, P-256, P-384 and P-521. Our approach allows gate-level comparisons to
recent resource estimates for Shor's factoring algorithm. The results also
support estimates given earlier by Proos and Zalka and indicate that, for
current parameters at comparable classical security levels, the number of
qubits required to tackle elliptic curves is less than for attacking RSA,
suggesting that indeed ECC is an easier target than RSA.Comment: 24 pages, 2 tables, 11 figures. v2: typos fixed and reference added.
ASIACRYPT 201
Conduction velocities in amphibian skeletal muscle fibres exposed to hyperosmotic extracellular solutions
Early quantitative analyses of conduction velocities in unmyelinated nerve studied in a constantly iso-osmotic volume conductor were extended to an analysis of the effects of varying extracellular osmolarities on conduction velocities of surface membrane action potentials in Rana esculenta skeletal muscle fibres. Previous papers had reported that skeletal muscle fibres exposed to a wide range of extracellular sucrose concentrations resemble perfect osmometers with increased extracellular osmolarity proportionally decreasing fibre volume and therefore diminishing fibre radius, a. However, classical electrolyte theory (Robinson and Stokes 1959, Electrolyte solutions 2nd edn. Butterworth & Co. pp 41–42) would then predict that the consequent increases in intracellular ionic strength would correspondingly decrease sarcoplasmic resistivity, Ri. An extension of the original cable analysis then demonstrated that the latter would precisely offset its expected effect of alterations in a on the fibre axial resistance, ri, and leave action potential conduction velocity constant. In contrast, other reports (Hodgkin and Nakajima J Physiol 221:105–120, 1972) had suggested that Riincreased with extracellular osmolarity, owing to alterations in cytosolic viscosity. This led to a prediction of a decreased conduction velocity. These opposing hypotheses were then tested in muscle fibres subject to just-suprathreshold stimulation at a Vaseline seal at one end and measuring action potentials and their first order derivatives, dV/dt, using 5–20 MΩ, 3 M KCl glass microelectrodes at defined distances away from the stimulus sites. Exposures to hyperosmotic, sucrose-containing, Ringer solutions then reversibly reduced both conduction velocity and maximum values of dV/dt. This was compatible with an increase in Ri in the event that conduction depended upon a discharge of membrane capacitance by propagating local circuit currents through initially passive electrical elements. Conduction velocity then showed graded decreases with increasing extracellular osmolarity from 250–750 mOsm. Action potential waveforms through these osmolarity changes remained similar, including both early surface and the late after-depolarisation events reflecting transverse tubular activation. Quantitative comparisons of reduced-χ 2 values derived from a comparison of these results and the differing predictions from the two hypotheses strongly favoured the hypothesis in which Riincreased rather than decreased with hyperosmolarity
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis
Macrophages abundantly found in the tumor microenvironment enhance malignancy(1). At metastatic sites a distinct population of metastasis associated macrophages (MAMs) promote tumor cell extravasation, seeding and persistent growth(2). Our study has defined the origin of these macrophages by showing Gr1+ inflammatory monocytes (IMs) are preferentially recruited to pulmonary metastases but not primary mammary tumors, a process also found for human IMs in pulmonary metastases of human breast cancer cells. The recruitment of these CCR2 (receptor for chemokine CCL2) expressing IMs and subsequently MAMs and their interaction with metastasizing tumor cells is dependent on tumor and stromal synthesized CCL2 (FigS1). Inhibition of CCL2/CCR2 signaling using anti-CCL2 antibodies blocks IM recruitment and inhibits metastasis in vivo and prolongs the survival of tumor-bearing mice. Depletion of tumor cell-derived CCL2 also inhibits metastatic seeding. IMs promote tumor cell extravasation in a process that requires monocyte-derived VEGF. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer (Fig S2)(3-6). Our data provides the mechanistic link between these two clinical associations and indicates new therapeutic targets for treating metastatic breast disease
Improved quantum circuits for elliptic curve discrete logarithms
We present improved quantum circuits for elliptic curve scalar
multiplication, the most costly component in Shor's algorithm to compute
discrete logarithms in elliptic curve groups. We optimize low-level components
such as reversible integer and modular arithmetic through windowing techniques
and more adaptive placement of uncomputing steps, and improve over previous
quantum circuits for modular inversion by reformulating the binary Euclidean
algorithm. Overall, we obtain an affine Weierstrass point addition circuit that
has lower depth and uses fewer gates than previous circuits. While previous
work mostly focuses on minimizing the total number of qubits, we present
various trade-offs between different cost metrics including the number of
qubits, circuit depth and -gate count. Finally, we provide a full
implementation of point addition in the Q# quantum programming language that
allows unit tests and automatic quantum resource estimation for all components.Comment: 22 pages, to appear in: Int'l Conf. on Post-Quantum Cryptography
(PQCrypto 2020
Human skeletal muscle plasmalemma alters its structure to change its Ca2+-handling following heavy-load resistance exercise
High-force eccentric exercise results in sustained increases in cytoplasmic Ca2+ levels ([Ca2+]cyto), which can cause damage to the muscle. Here we report that a heavy-load strength training bout greatly alters the structure of the membrane network inside the fibres, the tubular (t-) system, causing the loss of its predominantly transverse organization and an increase in vacuolation of its longitudinal tubules across adjacent sarcomeres. The transverse tubules and vacuoles displayed distinct Ca2+-handling properties. Both t-system components could take up Ca2+ from the cytoplasm but only transverse tubules supported store-operated Ca2+ entry. The retention of significant amounts of Ca2+ within vacuoles provides an effective mechanism to reduce the total content of Ca2+ within the fibre cytoplasm. We propose this ability can reduce or limit resistance exercise-induced, Ca2+-dependent damage to the fibre by the reduction of [Ca2+]cyto to help maintain fibre viability during the period associated with delayed onset muscle soreness
Contextual Query Using Bell Tests
Tests are essential in Information Retrieval and Data Mining in order to
evaluate the effectiveness of a query. An automatic measure tool intended to
exhibit the meaning of words in context has been developed and linked with
Quantum Theory, particularly entanglement. "Quantum like" experiments were
undertaken on semantic space based on the Hyperspace Analogue Language (HAL)
method. A quantum HAL model was implemented using state vectors issued from the
HAL matrix and query observables, testing a wide range of windows sizes. The
Bell parameter S, associating measures on two words in a document, was derived
showing peaks for specific window sizes. The peaks show maximum quantum
violation of the Bell inequalities and are document dependent. This new
correlation measure inspired by Quantum Theory could be promising for measuring
query relevance.Comment: 12 pages, 3 figure
- …