Beyond homozygosity mapping: family-control analysis based on Hamming distance for prioritizing variants in exome sequencing

A major challenge in current exome sequencing in autosomal recessive (AR) families is the lack of an effective method to prioritize single-nucleotide variants (SNVs). AR families are generally too small for linkage analysis, and length of homozygous regions is unreliable for identification of causative variants. Various common filtering steps usually result in a list of candidate variants that cannot be narrowed down further or ranked. To prioritize shortlisted SNVs we consider each homozygous candidate variant together with a set of SNVs flanking it. We compare the resulting array of genotypes between an affected family member and a number of control individuals and argue that, in a family, differences between family member and controls should be larger for a pathogenic variant and SNVs flanking it than for a random variant. We assess differences between arrays in two individuals by the Hamming distance and develop a suitable test statistic, which is expected to be large for a causative variant and flanking SNVs. We prioritize candidate variants based on this statistic and applied our approach to six patients with known pathogenic variants and found these to be in the top 2 to 10 percentiles of ranks

On the excitation of inertial modes in an experimental spherical Couette flow

Spherical Couette flow (flow between concentric rotating spheres) is one of flows under consideration for the laboratory magnetic dynamos. Recent experiments have shown that such flows may excite Coriolis restored inertial modes. The present work aims to better understand the properties of the observed modes and the nature of their excitation. Using numerical solutions describing forced inertial modes of a uniformly rotating fluid inside a spherical shell, we first identify the observed oscillations of the Couette flow with non-axisymmetric, retrograde, equatorially anti-symmetric inertial modes, confirming first attempts using a full sphere model. Although the model has no differential rotation, identification is possible because a large fraction of the fluid in a spherical Couette flow rotates rigidly. From the observed sequence of the excited modes appearing when the inner sphere is slowed down by step, we identify a critical Rossby number associated with a given mode and below which it is excited. The matching between this critical number and the one derived from the phase velocity of the numerically computed modes shows that these modes are excited by an instability likely driven by the critical layer that develops in the shear layer staying along the tangent cylinder of the inner sphere.Comment: 11 pages, 17 figure

Measurement of angular momentum transport in turbulent flow between independently rotating cylinders

We present measurements of the angular momentum flux (torque) in Taylor-Couette flow of water between independently rotating cylinders for all regions of the \(\Omega_1, \Omega_2\) parameter space at high Reynolds numbers, where $\Omega_1$ \(\Omega_2\) is the inner (outer) cylinder angular velocity. We find that the Rossby number Ro = \(\Omega_1 - \Omega_2\)/\Omega_2 fully determines the state and torque $G$ as compared to G(Ro = \infty) \equiv \Gi. The ratio G/\Gi is a linear function of $Ro^{-1}$ in four sections of the parameter space. For flows with radially-increasing angular momentum, our measured torques greatly exceed those of previous experiments [Ji \textit{et al.}, Nature, \textbf{444}, 343 (2006)], but agree with the analysis of Richard and Zahn [Astron. Astrophys., \textbf{347}, 734 (1999)].Comment: 4 pages, 4 figures, to appear in Physical Review Letter

Boolean Chaos

We observe deterministic chaos in a simple network of electronic logic gates that are not regulated by a clocking signal. The resulting power spectrum is ultra-wide-band, extending from dc to beyond 2 GHz. The observed behavior is reproduced qualitatively using an autonomously updating Boolean model with signal propagation times that depend on the recent history of the gates and filtering of pulses of short duration, whose presence is confirmed experimentally. Electronic Boolean chaos may find application as an ultra-wide-band source of radio wavesComment: 10 pages and 4 figur

Comprehensive User Engagement Sites (CUES) in Philadelphia: A Constructive Proposal

This paper is a study about Philadelphia’s comprehensive user engagement sites (CUESs) as the authors address and examine issues related to the upcoming implementation of a CUES while seeking solutions for its disputed questions and plans. Beginning with the federal drug schedules, the authors visit some of the medical and public health issues vis-à-vis safe injection facilities (SIFs). Insite, a successful Canadian SIF, has been thoroughly researched as it represents a paradigm for which a Philadelphia CUES can expand upon. Also, the existing criticisms against SIFs are revisited while critically unpackaged and responded to in favor of the establishment. In the main section, the authors propose the layout and services of the upcoming CUES, much of which would be in congruent to Vancouver’s Insite. On the other hand, the CUES would be distinct from Insite, as the authors emphasize, in that it will offer an information center run by individuals in recovery and place additional emphasis on early education for young healthcare professionals by providing them a platform to work at the site. The paper will also briefly investigate the implementation of a CUES site under an ethical scope of the Harm Reduction Theory. Lastly, the authors recommend some strategic plans that the Philadelphia City government may consider employing at this crucial stage

Collective patterns arising out of spatio-temporal chaos

We present a simple mathematical model in which a time averaged pattern emerges out of spatio-temporal chaos as a result of the collective action of chaotic fluctuations. Our evolution equation possesses spatial translational symmetry under a periodic boundary condition. Thus the spatial inhomogeneity of the statistical state arises through a spontaneous symmetry breaking. The transition from a state of homogeneous spatio-temporal chaos to one exhibiting spatial order is explained by introducing a collective viscosity which relates the averaged pattern with a correlation of the fluctuations.Comment: 11 pages (Revtex) + 5 figures (postscript