Validation of semi-analytical, semi-empirical covariance matrices for two-point correlation function for early DESI data

We present an extended validation of semi-analytical, semi-empirical covariance matrices for the two-point correlation function (2PCF) on simulated catalogs representative of luminous red galaxies (LRGs) data collected during the initial 2 months of operations of the Stage-IV ground-based Dark Energy Spectroscopic Instrument (DESI). We run the pipeline on multiple effective Zel'dovich (EZ) mock galaxy catalogs with the corresponding cuts applied and compare the results with the mock sample covariance to assess the accuracy and its fluctuations. We propose an extension of the previously developed formalism for catalogs processed with standard reconstruction algorithms. We consider methods for comparing covariance matrices in detail, highlighting their interpretation and statistical properties caused by sample variance, in particular, non-trivial expectation values of certain metrics even when the external covariance estimate is perfect. With improved mocks and validation techniques, we confirm a good agreement between our predictions and sample covariance. This allows one to generate covariance matrices for comparable data sets without the need to create numerous mock galaxy catalogs with matching clustering, only requiring 2PCF measurements from the data itself. The code used in this paper is publicly available at https://github.com/oliverphilcox/RascalC

Standardized ultrasound evaluation of carotid stenosis for clinical trials: University of Washington Ultrasound Reading Center

<p>Abstract</p> <p>Introduction</p> <p>Serial monitoring of patients participating in clinical trials of carotid artery therapy requires noninvasive precision methods that are inexpensive, safe and widely available. Noninvasive ultrasonic duplex Doppler velocimetry provides a precision method that can be used for recruitment qualification, pre-treatment classification and post treatment surveillance for remodeling and restenosis. The University of Washington Ultrasound Reading Center (UWURC) provides a uniform examination protocol and interpretation of duplex Doppler velocity measurements.</p> <p>Methods</p> <p>Doppler waveforms from 6 locations along the common carotid and internal carotid artery path to the brain plus the external carotid and vertebral arteries on each side using a Doppler examination angle of 60 degrees are evaluated. The UWURC verifies all measurements against the images and waveforms for the database, which includes pre-procedure, post-procedure and annual follow-up examinations. Doppler angle alignment errors greater than 3 degrees and Doppler velocity measurement errors greater than 0.05 m/s are corrected.</p> <p>Results</p> <p>Angle adjusted Doppler velocity measurements produce higher values when higher Doppler examination angles are used. The definition of peak systolic velocity varies between examiners when spectral broadening due to turbulence is present. Examples of measurements are shown.</p> <p>Discussion</p> <p>Although ultrasonic duplex Doppler methods are widely used in carotid artery diagnosis, there is disagreement about how the examinations should be performed and how the results should be validated. In clinical trails, a centralized reading center can unify the methods. Because the goals of research examinations are different from those of clinical examinations, screening and diagnostic clinical examinations may require fewer velocity measurements.</p

Uncovering Genes with Divergent mRNA-Protein Dynamics in Streptomyces coelicolor

Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in many studies, examples of divergent trends are frequently observed. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in microbiology as they pertain to the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides (iTRAQ™) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes exhibit mRNA-protein discordance in a similar fashion. Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures

Development of the vertebrate forebrain and craniofacial structures are intimately linked processes, the coordinated growth of these tissues being required to ensure normal head formation. In this study, we identify five small subsets of progenitors expressing the transcription factor dbx1 in the cephalic region of developing mouse embryos at E8.5. Using genetic tracing we show that dbx1-expressing cells and their progeny have a modest contribution to the forebrain and face tissues. However, their genetic ablation triggers extensive and non cell-autonomous apoptosis as well as a decrease in proliferation in surrounding tissues, resulting in the progressive loss of most of the forebrain and frontonasal structures. Targeted ablation of the different subsets reveals that the very first dbx1-expressing progenitors are critically required for the survival of anterior neural tissues, the production and/or migration of cephalic neural crest cells and, ultimately, forebrain formation. In addition, we find that the other subsets, generated at slightly later stages, each play a specific function during head development and that their coordinated activity is required for accurate craniofacial morphogenesis. Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner

Astrometric Calibration and Performance of the Dark Energy Spectroscopic Instrument Focal Plane

The Dark Energy Spectroscopic Instrument, consisting of 5020 robotic fiber positioners and associated systems on the Mayall telescope at Kitt Peak, Arizona, is carrying out a survey to measure the spectra of 40 million galaxies and quasars and produce the largest 3D map of the universe to date. The primary science goal is to use baryon acoustic oscillations to measure the expansion history of the universe and the time evolution of dark energy. A key function of the online control system is to position each fiber on a particular target in the focal plane with an accuracy of 11 μm rms 2D. This paper describes the set of software programs used to perform this function along with the methods used to validate their performance

Comparative genetic, proteomic and phosphoproteomic analysis of C. <i>elegans </i>embryos with a focus on <i>ham</i>-1/STOX and <i>pig</i>-1/MELK in dopaminergic neuron development

Asymmetric cell divisions are required for cellular diversity and defects can lead to altered daughter cell fates and numbers. In a genetic screen for C. elegans mutants with defects in dopaminergic head neuron specification or differentiation, we isolated a new allele of the transcription factor HAM-1 [HSN (Hermaphrodite-Specific Neurons) Abnormal Migration]. Loss of both HAM-1 and its target, the kinase PIG-1 [PAR-1(I)-like Gene], leads to abnormal dopaminergic head neuron numbers. We identified discrete genetic relationships between ham-1, pig-1 and apoptosis pathway genes in dopaminergic head neurons. We used an unbiased, quantitative mass spectrometry-based proteomics approach to characterise direct and indirect protein targets and pathways that mediate the effects of PIG-1 kinase loss in C. elegans embryos. Proteins showing changes in either abundance, or phosphorylation levels, between wild-type and pig-1 mutant embryos are predominantly connected with processes including cell cycle, asymmetric cell division, apoptosis and actomyosin-regulation. Several of these proteins play important roles in C. elegans development. Our data provide an in-depth characterisation of the C. elegans wild-type embryo proteome and phosphoproteome and can be explored via the Encyclopedia of Proteome Dynamics (EPD) - an open access, searchable online database

SIRT2 Ablation Has No Effect on Tubulin Acetylation in Brain, Cholesterol Biosynthesis or the Progression of Huntington's Disease Phenotypes In Vivo

Huntington's disease (HD) is a devastating neurodegenerative disorder for which there are no disease-modifying treatments. The molecular pathogenesis of HD is complex and many mechanisms and cellular processes have been proposed as potential sites of therapeutic intervention. However, prior to embarking on drug development initiatives, it is essential that therapeutic targets can be validated in mammalian models of HD. Previous studies in invertebrate and cell culture HD models have suggested that inhibition of SIRT2 could have beneficial consequences on disease progression. SIRT2 is a NAD[superscript +]-dependent deacetylase that has been proposed to deacetylate α-tubulin, histone H4 K16 and to regulate cholesterol biogenesis – a pathway which is dysregulated in HD patients and HD mouse models. We have utilized mice in which SIRT2 has been reduced or ablated to further explore the function of SIRT2 and to assess whether SIRT2 loss has a beneficial impact on disease progression in the R6/2 mouse model of HD. Surprisingly we found that reduction or loss of SIRT2 had no effect on the acetylation of α-tubulin or H4K16 or on cholesterol biosynthesis in the brains of wild type mice. Equally, genetic reduction or ablation of SIRT2 had no effect on HD progression as assessed by a battery of physiological and behavioural tests. Furthermore, we observed no change in aggregate load or levels of soluble mutant huntingtin transprotein. Intriguingly, neither the constitutive genetic loss nor acute pharmacological inhibition of SIRT2 affected the expression of cholesterol biosynthesis enzymes in the context of HD. Therefore, we conclude that SIRT2 inhibition does not modify disease progression in the R6/2 mouse model of HD and SIRT2 inhibition should not be prioritised as a therapeutic option for HD.American Parkinson Disease Association, Inc. (Fellowship)Johnson & Johnson. Pharmaceutical Research & Development (Fellowship

Target Selection and Validation of DESI Quasars

The Dark Energy Spectroscopic Instrument (DESI) survey will measure large-scale structures using quasars as direct tracers of dark matter in the redshift range 0.9 2.1. We present several methods to select candidate quasars for DESI, using input photometric imaging in three optical bands (g, r, z) from the DESI Legacy Imaging Surveys and two infrared bands (W1, W2) from the Wide-field Infrared Survey Explorer. These methods were extensively tested during the Survey Validation of DESI. In this paper, we report on the results obtained with the different methods and present the selection we optimized for the DESI main survey. The final quasar target selection is based on a random forest algorithm and selects quasars in the magnitude range of 16.5 2.1), exceeding the project requirements by 20%. The redshift distribution of the selected quasars is in excellent agreement with quasar luminosity function predictions

Protective Effect of Tetrahydroxystilbene Glucoside on 6-OHDA-Induced Apoptosis in PC12 Cells through the ROS-NO Pathway

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease. The molecule, 2,3,5,4′-tetrahydr- oxystilbene-2-O-β-D-glucoside (TSG), is a potent antioxidant derived from the Chinese herb, Polygonum multiflorum Thunb. In this study, we investigated the protective effect of TSG against 6-hydroxydopamine-induced apoptosis in rat adrenal pheochromocytoma PC12 cells and the possible mechanisms. Our data demonstrated that TSG significantly reversed the 6-hydroxydopamine-induced decrease in cell viability, prevented 6-hydroxydopamine-induced changes in condensed nuclei and decreased the percentage of apoptotic cells in a dose-dependent manner. In addition, TSG slowed the accumulation of intracellular reactive oxygen species and nitric oxide, counteracted the overexpression of inducible nitric oxide syntheses as well as neuronal nitric oxide syntheses, and also reduced the level of protein-bound 3-nitrotyrosine. These results demonstrate that the protective effects of TSG on rat adrenal pheochromocytoma PC12 cells are mediated, at least in part, by the ROS-NO pathway. Our results indicate that TSG may be effective in providing protection against neurodegenerative diseases associated with oxidative stress