k-d Darts: Sampling by k-Dimensional Flat Searches

We formalize the notion of sampling a function using k-d darts. A k-d dart is a set of independent, mutually orthogonal, k-dimensional subspaces called k-d flats. Each dart has d choose k flats, aligned with the coordinate axes for efficiency. We show that k-d darts are useful for exploring a function's properties, such as estimating its integral, or finding an exemplar above a threshold. We describe a recipe for converting an algorithm from point sampling to k-d dart sampling, assuming the function can be evaluated along a k-d flat. We demonstrate that k-d darts are more efficient than point-wise samples in high dimensions, depending on the characteristics of the sampling domain: e.g. the subregion of interest has small volume and evaluating the function along a flat is not too expensive. We present three concrete applications using line darts (1-d darts): relaxed maximal Poisson-disk sampling, high-quality rasterization of depth-of-field blur, and estimation of the probability of failure from a response surface for uncertainty quantification. In these applications, line darts achieve the same fidelity output as point darts in less time. We also demonstrate the accuracy of higher dimensional darts for a volume estimation problem. For Poisson-disk sampling, we use significantly less memory, enabling the generation of larger point clouds in higher dimensions.Comment: 19 pages 16 figure

Green Fluorescent Protein in the sea urchin: new experimental approaches to transcriptional regulatory analysis in embryos and larvae

The use of Green Fluorescent Protein (GFP) as a reporter for expression transgenes opens the way to several new experimental strategies for the study of gene regulation in sea urchin development. A GFP coding sequence was associated with three different previously studied cis-regulatory systems, viz those of the SM50 gene, expressed in skeletogenic mesenchyme, the CyIIa gene, expressed in archenteron, skeletogenic and secondary mesenchyme, and the Endo16 gene, expressed in vegetal plate, archenteron and midgut. We demonstrate that the sensitivity with which expression can be detected is equal to or greater than that of whole-mount in situ hybridization applied to detection of CAT mRNA synthesized under the control of the same cis-regulatory systems. However, in addition to the important feature that it can be visualized nondestructively in living embryos, GFP has other advantages. First, it freely diffuses even within fine cytoplasmic cables, and thus reveals connections between cells, which in sea urchin embryos is particularly useful for observations on regulatory systems that operate in the syncytial skeletogenic mesenchyme. Second, GFP expression can be dramatically visualized in postembryonic larval tissues. This brings postembryonic larval developmental processes for the first time within the easy range of gene transfer analyses. Third, GFP permits identification and segregation of embryos in which the clonal incorporation of injected DNA has occurred in any particular desired region of the embryo. Thus, we show explicitly that, as expected, GFP transgenes are incorporated in the same nuclei together with other transgenes with which they are co-injected

Gunrock: GPU Graph Analytics

For large-scale graph analytics on the GPU, the irregularity of data access and control flow, and the complexity of programming GPUs, have presented two significant challenges to developing a programmable high-performance graph library. "Gunrock", our graph-processing system designed specifically for the GPU, uses a high-level, bulk-synchronous, data-centric abstraction focused on operations on a vertex or edge frontier. Gunrock achieves a balance between performance and expressiveness by coupling high performance GPU computing primitives and optimization strategies with a high-level programming model that allows programmers to quickly develop new graph primitives with small code size and minimal GPU programming knowledge. We characterize the performance of various optimization strategies and evaluate Gunrock's overall performance on different GPU architectures on a wide range of graph primitives that span from traversal-based algorithms and ranking algorithms, to triangle counting and bipartite-graph-based algorithms. The results show that on a single GPU, Gunrock has on average at least an order of magnitude speedup over Boost and PowerGraph, comparable performance to the fastest GPU hardwired primitives and CPU shared-memory graph libraries such as Ligra and Galois, and better performance than any other GPU high-level graph library.Comment: 52 pages, invited paper to ACM Transactions on Parallel Computing (TOPC), an extended version of PPoPP'16 paper "Gunrock: A High-Performance Graph Processing Library on the GPU

Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis

Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in protecting against such chronic disorders have been examined previously. Sulforaphane is a naturally occurring antioxidant. Herein, we explore whether SFX-01®, a stable synthetic form of sulforaphane, modifies gait, bone architecture and slows/reverses articular cartilage destruction in a spontaneous OA model in STR/Ort mice. Sixteen mice (n = 8/group) were orally treated for 3 months with either 100 mg/kg SFX-01® or vehicle. Gait was recorded, tibiae were microCT scanned and analysed. OA lesion severity was graded histologically. The effect of SFX-01® on bone turnover markers in vivo was complemented by in vitro bone formation and resorption assays. Analysis revealed development of OA-related gait asymmetry in vehicle-treated STR/Ort mice, which did not emerge in SFX-01®-treated mice. We found significant improvements in trabecular and cortical bone. Despite these marked improvements, we found that histologically-graded OA severity in articular cartilage was unmodified in treated mice. These changes are also reflected in anabolic and anti-catabolic actions of SFX-01® treatment as reflected by alteration in serum markers as well as changes in primary osteoblast and osteoclast-like cells in vitro. We report that SFX-01® improves bone microarchitecture in vivo, produces corresponding changes in bone cell behaviour in vitro and leads to greater symmetry in gait, without marked effects on cartilage lesion severity in STR/Ort osteoarthritic mice. Our findings support both osteotrophic roles and novel beneficial gait effects for SFX-01® in this model of spontaneous OA

The XMM Cluster Survey: Evidence for energy injection at high redshift from evolution of the X-ray luminosity-temperature relation

We measure the evolution of the X-ray luminosity-temperature (L_X-T) relation since z~1.5 using a sample of 211 serendipitously detected galaxy clusters with spectroscopic redshifts drawn from the XMM Cluster Survey first data release (XCS-DR1). This is the first study spanning this redshift range using a single, large, homogeneous cluster sample. Using an orthogonal regression technique, we find no evidence for evolution in the slope or intrinsic scatter of the relation since z~1.5, finding both to be consistent with previous measurements at z~0.1. However, the normalisation is seen to evolve negatively with respect to the self-similar expectation: we find E(z)^{-1} L_X = 10^{44.67 +/- 0.09} (T/5)^{3.04 +/- 0.16} (1+z)^{-1.5 +/- 0.5}, which is within 2 sigma of the zero evolution case. We see milder, but still negative, evolution with respect to self-similar when using a bisector regression technique. We compare our results to numerical simulations, where we fit simulated cluster samples using the same methods used on the XCS data. Our data favour models in which the majority of the excess entropy required to explain the slope of the L_X-T relation is injected at high redshift. Simulations in which AGN feedback is implemented using prescriptions from current semi-analytic galaxy formation models predict positive evolution of the normalisation, and differ from our data at more than 5 sigma. This suggests that more efficient feedback at high redshift may be needed in these models.Comment: Accepted for publication in MNRAS; 12 pages, 6 figures; added references to match published versio

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCβ3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCβ3 and the TRPV1 channel; 2) serotonin, or a selective agonist, α-methyl-serotonin (α-Me-5-HT), requires the presence of PLCβ3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCβ3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD^+ neurons that represent ≈90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1+ nociceptors led to a significant behavioral deficit for pruritogens, including α-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways

Non-Singular Solutions for S-branes

Exact, non-singular, time-dependent solutions of Maxwell-Einstein gravity with and without dilatons are constructed by double Wick rotating a variety of static, axisymmetric solutions. This procedure transforms arrays of charged or neutral black holes into s-brane (spacelike brane) solutions, i.e. extended, short-lived spacelike defects. Along the way, new static solutions corresponding to arrays of alternating-charge Reissner-Nordstrom black holes, as well as their dilatonic generalizations, are found. Their double Wick rotation yields s-brane solutions which are periodic in imaginary time and potential large-N duals for the creation/decay of unstable D-branes in string theory.Comment: 21 pages, 3 figure

Physical restraint in residential child care : the experiences of young people and residential workers

There have long been concerns about the use of physical restraint in residential care. This paper presents the findings of a qualitative study which explores the experiences of children, young people and residential workers about physical restraint. The research identifies the dilemmas and ambiguities for both staff and young people, and participants discuss the situations where they feel physical restraint is appropriate as well as their concerns about unjustified or painful restraints. They describe the negative emotions involved in restraint but also those situations where, through positive relationships and trust, restraint can help young people through unsafe situations