Three-Dimensional GPU-Accelerated Active Contours for Automated Localization of Cells in Large Images

Cell segmentation in microscopy is a challenging problem, since cells are often asymmetric and densely packed. This becomes particularly challenging for extremely large images, since manual intervention and processing time can make segmentation intractable. In this paper, we present an efficient and highly parallel formulation for symmetric three-dimensional (3D) contour evolution that extends previous work on fast two-dimensional active contours. We provide a formulation for optimization on 3D images, as well as a strategy for accelerating computation on consumer graphics hardware. The proposed software takes advantage of Monte-Carlo sampling schemes in order to speed up convergence and reduce thread divergence. Experimental results show that this method provides superior performance for large 2D and 3D cell segmentation tasks when compared to existing methods on large 3D brain images

Airborne particulate matter and mitochondrial damage: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Oxidative stress generation is a primary mechanism mediating the effects of Particulate Matter (PM) on human health. Although mitochondria are both the major intracellular source and target of oxidative stress, the effect of PM on mitochondria has never been evaluated in exposed individuals.</p> <p>Methods</p> <p>In 63 male healthy steel workers from Brescia, Italy, studied between April and May 2006, we evaluated whether exposure to PM was associated with increased mitochondrial DNA copy number (MtDNAcn), an established marker of mitochondria damage and malfunctioning. Relative MtDNAcn (RMtDNAcn) was determined by real-time PCR in blood DNA obtained on the 1^st(time 1) and 4^thday (time 2) of the same work week. Individual exposures to PM₁₀, PM₁, coarse particles (PM₁₀-PM₁) and airborne metal components of PM₁₀(chromium, lead, arsenic, nickel, manganese) were estimated based on measurements in the 11 work areas and time spent by the study subjects in each area.</p> <p>Results</p> <p>RMtDNAcn was higher on the 4^thday (mean = 1.31; 95%CI = 1.22 to 1.40) than on the 1^stday of the work week (mean = 1.09; 95%CI = 1.00 to 1.17). PM exposure was positively associated with RMtDNAcn on either the 4^th(PM₁₀: β = 0.06, 95%CI = -0.06 to 0.17; PM₁: β = 0.08, 95%CI = -0.08 to 0.23; coarse: β = 0.06, 95%CI = -0.06 to 0.17) or the 1^stday (PM₁₀: β = 0.18, 95%CI = 0.09 to 0.26; PM₁: β = 0.23, 95%CI = 0.11 to 0.35; coarse: β = 0.17, 95%CI = 0.09 to 0.26). Metal concentrations were not associated with RMtDNAcn.</p> <p>Conclusions</p> <p>PM exposure is associated with damaged mitochondria, as reflected in increased MtDNAcn. Damaged mitochondria may intensify oxidative-stress production and effects.</p

L. Evidence of spatial variation of the polarized thermal dust spectral energy distribution and implications for CMB B-mode analysis

Planck Collaboration.The characterization of the Galactic foregrounds has been shown to be the main obstacle in thechallenging quest to detect primordial B-modes in the polarized microwave sky. We make use of the Planck-HFI 2015 data release at high frequencies to place new constraints on the properties of the polarized thermal dust emission at high Galactic latitudes. Here, we specifically study the spatial variability of the dust polarized spectral energy distribution (SED), and its potential impact on the determination of the tensor-to-scalar ratio, r. We use the correlation ratio of the angular power spectra between the 217 and 353 GHz channels as a tracer of these potential variations, computed on different high Galactic latitude regions, ranging from 80% to 20% of the sky. The new insight from Planck data is a departure of the correlation ratio from unity that cannot be attributed to a spurious decorrelation due to the cosmic microwave background, instrumental noise, or instrumental systematics. The effect is marginally detected on each region, but the statistical combination of all the regions gives more than 99% confidence for this variation in polarized dust properties. In addition, we show that the decorrelation increases when there is a decrease in the mean column density of the region of the sky being considered, and we propose a simple power-law empirical model for this dependence, which matches what is seen in the Planck data. We explore the effect that this measured decorrelation has on simulations of the BICEP2-Keck Array/Planck analysis and show that the 2015 constraints from these data still allow a decorrelation between the dust at 150 and 353 GHz that is compatible with our measured value. Finally, using simplified models, we show that either spatial variation of the dust SED or of the dust polarization angle are able to produce decorrelations between 217 and 353 GHz data similar to the values we observe in the data.The Planck Collaboration acknowledges the support of: ESA; CNES, and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, J.A., and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); ERC and PRACE (EU). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement No. 267934.Peer Reviewe

Robust Cell Detection for Large-Scale 3D Microscopy Using GPU-Accelerated Iterative Voting

High-throughput imaging techniques, such as Knife-Edge Scanning Microscopy (KESM),are capable of acquiring three-dimensional whole-organ images at sub-micrometer resolution. These images are challenging to segment since they can exceed several terabytes (TB) in size, requiring extremely fast and fully automated algorithms. Staining techniques are limited to contrast agents that can be applied to large samples and imaged in a single pass. This requires maximizing the number of structures labeled in a single channel, resulting in images that are densely packed with spatial features. In this paper, we propose a three-dimensional approach for locating cells based on iterative voting. Due to the computational complexity of this algorithm, a highly efficient GPU implementation is required to make it practical on large data sets. The proposed algorithm has a limited number of input parameters and is highly parallel

Expression of Baculovirus Late and Very Late Genes Depends on LEF-4, a Component of the Viral RNA Polymerase Whose Guanyltransferase Function Is Essential

Baculovirus lef-4 encodes one subunit of the viral RNA polymerase. Here, we demonstrate the essential nature of LEF-4 by RNA interference and bacmid knockout technology. Silencing of LEF-4 in wild-type virus-infected cells suppressed expression of structural genes, while early expression was unaffected, demonstrating its essential role in late gene expression. After transfection of insect cells with lef-4 mutant bacmid, no viral progeny was produced, further defining its central role in infection. Cotransfection with wild-type lef-4 plasmid restored normal replication, but plasmid encoding a guanyltransferase-deficient version failed to rescue. These results emphasize the importance of the mRNA capping function of LEF-4

Presentation_1_Robust Cell Detection for Large-Scale 3D Microscopy Using GPU-Accelerated Iterative Voting.PDF

<p>High-throughput imaging techniques, such as Knife-Edge Scanning Microscopy (KESM),are capable of acquiring three-dimensional whole-organ images at sub-micrometer resolution. These images are challenging to segment since they can exceed several terabytes (TB) in size, requiring extremely fast and fully automated algorithms. Staining techniques are limited to contrast agents that can be applied to large samples and imaged in a single pass. This requires maximizing the number of structures labeled in a single channel, resulting in images that are densely packed with spatial features. In this paper, we propose a three-dimensional approach for locating cells based on iterative voting. Due to the computational complexity of this algorithm, a highly efficient GPU implementation is required to make it practical on large data sets. The proposed algorithm has a limited number of input parameters and is highly parallel.</p

Disrupted Membrane Homeostasis and Accumulation of Ubiquitinated Proteins in a Mouse Model of Infantile Neuroaxonal Dystrophy Caused by PLA2G6 Mutations

Mutations in the PLA2G6 gene, which encodes group VIA calcium-independent phospholipase A2 (iPLA2β), were recently identified in patients with infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation. A pathological hallmark of these childhood neurodegenerative diseases is the presence of distinctive spheroids in distal axons that contain accumulated membranes. We used iPLA2β-KO mice generated by homologous recombination to investigate neurodegenerative consequences of PLA2G6 mutations. iPLA2β-KO mice developed age-dependent neurological impairment that was evident in rotarod, balance, and climbing tests by 13 months of age. The primary abnormality underlying this neurological impairment was the formation of spheroids containing tubulovesicular membranes remarkably similar to human INAD. Spheroids were strongly labeled with anti-ubiquitin antibodies. Accumulation of ubiquitinated protein in spheroids was evident in some brain regions as early as 4 months of age, and the onset of motor impairment correlated with a dramatic increase in ubiquitin-positive spheroids throughout the neuropil in nearly all brain regions. Furthermore accumulating ubiquitinated proteins were observed primarily in insoluble fractions of brain tissue, implicating protein aggregation in this pathogenic process. These results indicate that loss of iPLA2β causes age-dependent impairment of axonal membrane homeostasis and protein degradation pathways, leading to age-dependent neurological impairment. iPLA2β-KO mice will be useful for further studies of pathogenesis and experimental interventions in INAD and neurodegeneration with brain iron accumulation

NAD+-dependent Deacetylase SIRT3 Regulates Mitochondrial Protein Synthesis by Deacetylation of the Ribosomal Protein MRPL10*

A member of the sirtuin family of NAD+-dependent deacetylases, SIRT3, is located in mammalian mitochondria and is important for regulation of mitochondrial metabolism, cell survival, and longevity. In this study, MRPL10 (mitochondrial ribosomal protein L10) was identified as the major acetylated protein in the mitochondrial ribosome. Ribosome-associated SIRT3 was found to be responsible for deacetylation of MRPL10 in an NAD+-dependent manner. We mapped the acetylated Lys residues by tandem mass spectrometry and determined the role of these residues in acetylation of MRPL10 by site-directed mutagenesis. Furthermore, we observed that the increased acetylation of MRPL10 led to an increase in translational activity of mitochondrial ribosomes in Sirt3−/− mice. In a similar manner, ectopic expression and knockdown of SIRT3 in C2C12 cells resulted in the suppression and enhancement of mitochondrial protein synthesis, respectively. Our findings constitute the first evidence for the regulation of mitochondrial protein synthesis by the reversible acetylation of the mitochondrial ribosome and characterize MRPL10 as a novel substrate of the NAD+-dependent deacetylase, SIRT3