Raw ODEC Bathy2000 CHIRP subbottom profiler - CHIRP high-resolution Seismic Profile data for the U.S. Arctic Continental Margin.

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — ODEC Bathy2000 CHIRP subbottom profiler - CHIRP high-resolution Seismic Profile data were collected in Raw ODEC Bathy2000 CHIRP dat Datagram Format.

Raw ODEC Bathy2000 CHIRP subbottom profiler - CHIRP high-resolution Seismic Profile data for the Chukchi Cap and Arctic Ocean.

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — ODEC Bathy2000 CHIRP subbottom profiler - CHIRP high-resolution Seismic Profile data were collected in Raw ODEC Bathy2000 CHIRP dat Datagram Format.

Development of temperature profile sensor at high temporal and spatial resolution

International Nuclear Information System (INIS)

Takiguchi, Hiroki; Furuya, Masahiro; Arai, Takahiro

2017-01-01

In order to quantify thermo-physical flow field for the industrial applications such as nuclear and chemical reactors, high temporal and spatial measurements for temperature, pressure, phase velocity, viscosity and so on are required to validate computational fluid dynamics (CFD) and subchannel analyses. The paper proposes a novel temperature profile sensor, which can acquire temperature distribution in water at high temporal (a millisecond) and spatial (millimeter) resolutions. The devised sensor acquires electric conductance between transmitter and receiver wires, which is a function of temperature. The sensor comprise wire mesh structure for multipoint and simultaneous temperature measurement in water, which indicated that three-dimensional temperature distribution can be detected in flexible resolutions. For the demonstration of the principle, temperature profile in water was estimated according to pre-determined temperature calibration line against time-averaged impedance. The 16×16 grid sensor visualized fast and multi-dimensional mixing process of a hot water jet into a cold water pool. (author)

Using DNase Hi-C techniques to map global and local three-dimensional genome architecture at high resolution.

Science.gov (United States)

Ma, Wenxiu; Ay, Ferhat; Lee, Choli; Gulsoy, Gunhan; Deng, Xinxian; Cook, Savannah; Hesson, Jennifer; Cavanaugh, Christopher; Ware, Carol B; Krumm, Anton; Shendure, Jay; Blau, C Anthony; Disteche, Christine M; Noble, William S; Duan, ZhiJun

2018-06-01

The folding and three-dimensional (3D) organization of chromatin in the nucleus critically impacts genome function. The past decade has witnessed rapid advances in genomic tools for delineating 3D genome architecture. Among them, chromosome conformation capture (3C)-based methods such as Hi-C are the most widely used techniques for mapping chromatin interactions. However, traditional Hi-C protocols rely on restriction enzymes (REs) to fragment chromatin and are therefore limited in resolution. We recently developed DNase Hi-C for mapping 3D genome organization, which uses DNase I for chromatin fragmentation. DNase Hi-C overcomes RE-related limitations associated with traditional Hi-C methods, leading to improved methodological resolution. Furthermore, combining this method with DNA capture technology provides a high-throughput approach (targeted DNase Hi-C) that allows for mapping fine-scale chromatin architecture at exceptionally high resolution. Hence, targeted DNase Hi-C will be valuable for delineating the physical landscapes of cis-regulatory networks that control gene expression and for characterizing phenotype-associated chromatin 3D signatures. Here, we provide a detailed description of method design and step-by-step working protocols for these two methods. Copyright © 2018 Elsevier Inc. All rights reserved.

High-Resolution Microbiome Profiling for Detection and Tracking of Salmonella enterica

Directory of Open Access Journals (Sweden)

Christopher J. Grim

2017-08-01

Full Text Available 16S rRNA community profiling continues to be a useful tool to study microbiome composition and dynamics, in part due to advances in next generation sequencing technology that translate into reductions in cost. Reliable taxonomic identification to the species-level, however, remains difficult, especially for short-read sequencing platforms, due to incomplete coverage of the 16S rRNA gene. This is especially true for Salmonella enterica, which is often found as a low abundant member of the microbial community, and is often found in combination with several other closely related enteric species. Here, we report on the evaluation and application of Resphera Insight, an ultra-high resolution taxonomic assignment algorithm for 16S rRNA sequences to the species level. The analytical pipeline achieved 99.7% sensitivity to correctly identify S. enterica from WGS datasets extracted from the FDA GenomeTrakr Bioproject, while demonstrating 99.9% specificity over other Enterobacteriaceae members. From low-diversity and low-complexity samples, namely ice cream, the algorithm achieved 100% specificity and sensitivity for Salmonella detection. As demonstrated using cilantro and chili powder, for highly complex and diverse samples, especially those that contain closely related species, the detection threshold will likely have to be adjusted higher to account for misidentifications. We also demonstrate the utility of this approach to detect Salmonella in the clinical setting, in this case, bloodborne infections.

High-resolution genetic maps of Eucalyptus improve Eucalyptus grandis genome assembly.

Science.gov (United States)

Bartholomé, Jérôme; Mandrou, Eric; Mabiala, André; Jenkins, Jerry; Nabihoudine, Ibouniyamine; Klopp, Christophe; Schmutz, Jeremy; Plomion, Christophe; Gion, Jean-Marc

2015-06-01

Genetic maps are key tools in genetic research as they constitute the framework for many applications, such as quantitative trait locus analysis, and support the assembly of genome sequences. The resequencing of the two parents of a cross between Eucalyptus urophylla and Eucalyptus grandis was used to design a single nucleotide polymorphism (SNP) array of 6000 markers evenly distributed along the E. grandis genome. The genotyping of 1025 offspring enabled the construction of two high-resolution genetic maps containing 1832 and 1773 markers with an average marker interval of 0.45 and 0.5 cM for E. grandis and E. urophylla, respectively. The comparison between genetic maps and the reference genome highlighted 85% of collinear regions. A total of 43 noncollinear regions and 13 nonsynthetic regions were detected and corrected in the new genome assembly. This improved version contains 4943 scaffolds totalling 691.3 Mb of which 88.6% were captured by the 11 chromosomes. The mapping data were also used to investigate the effect of population size and number of markers on linkage mapping accuracy. This study provides the most reliable linkage maps for Eucalyptus and version 2.0 of the E. grandis genome. © 2014 CIRAD. New Phytologist © 2014 New Phytologist Trust.

Development of a high-resolution electron-beam profile monitor using Fresnel zone plates

International Nuclear Information System (INIS)

Nakamura, Norio; Sakai, Hiroshi; Muto, Toshiya; Hayano, Hitoshi

2004-01-01

We present a high-resolution and real-time beam profile monitor using Fresnel zone plates (FZPs) developed in the KEK-ATF damping ring. The monitor system has an X-ray imaging optics with two FZPs. In this monitor, the synchrotron radiation from the electron beam at the bending magnet is monochromatized by a crystal monochromator and the transverse electron beam image is twenty-times magnified by the two FZPs and detected on an X-ray CCD camera. The expected spatial resolution for the selected photon energy of 3.235 keV is less than 1 μm. With the beam profile monitor, we succeeded in obtaining a clear electron-beam image and measuring the extremely small beam size less than 10 μm. It is greatly expected that the beam profile monitor will be used in high-brilliance light sources and low-emittance accelerators. (author)

A multi-sample based method for identifying common CNVs in normal human genomic structure using high-resolution aCGH data.

Directory of Open Access Journals (Sweden)

Chihyun Park

Full Text Available BACKGROUND: It is difficult to identify copy number variations (CNV in normal human genomic data due to noise and non-linear relationships between different genomic regions and signal intensity. A high-resolution array comparative genomic hybridization (aCGH containing 42 million probes, which is very large compared to previous arrays, was recently published. Most existing CNV detection algorithms do not work well because of noise associated with the large amount of input data and because most of the current methods were not designed to analyze normal human samples. Normal human genome analysis often requires a joint approach across multiple samples. However, the majority of existing methods can only identify CNVs from a single sample. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a multi-sample-based genomic variations detector (MGVD that uses segmentation to identify common breakpoints across multiple samples and a k-means-based clustering strategy. Unlike previous methods, MGVD simultaneously considers multiple samples with different genomic intensities and identifies CNVs and CNV zones (CNVZs; CNVZ is a more precise measure of the location of a genomic variant than the CNV region (CNVR. CONCLUSIONS AND SIGNIFICANCE: We designed a specialized algorithm to detect common CNVs from extremely high-resolution multi-sample aCGH data. MGVD showed high sensitivity and a low false discovery rate for a simulated data set, and outperformed most current methods when real, high-resolution HapMap datasets were analyzed. MGVD also had the fastest runtime compared to the other algorithms evaluated when actual, high-resolution aCGH data were analyzed. The CNVZs identified by MGVD can be used in association studies for revealing relationships between phenotypes and genomic aberrations. Our algorithm was developed with standard C++ and is available in Linux and MS Windows format in the STL library. It is freely available at: http://embio.yonsei.ac.kr/~Park/mgvd.php.

Plastid: nucleotide-resolution analysis of next-generation sequencing and genomics data.

Science.gov (United States)

Dunn, Joshua G; Weissman, Jonathan S

2016-11-22

Next-generation sequencing (NGS) informs many biological questions with unprecedented depth and nucleotide resolution. These assays have created a need for analytical tools that enable users to manipulate data nucleotide-by-nucleotide robustly and easily. Furthermore, because many NGS assays encode information jointly within multiple properties of read alignments - for example, in ribosome profiling, the locations of ribosomes are jointly encoded in alignment coordinates and length - analytical tools are often required to extract the biological meaning from the alignments before analysis. Many assay-specific pipelines exist for this purpose, but there remains a need for user-friendly, generalized, nucleotide-resolution tools that are not limited to specific experimental regimes or analytical workflows. Plastid is a Python library designed specifically for nucleotide-resolution analysis of genomics and NGS data. As such, Plastid is designed to extract assay-specific information from read alignments while retaining generality and extensibility to novel NGS assays. Plastid represents NGS and other biological data as arrays of values associated with genomic or transcriptomic positions, and contains configurable tools to convert data from a variety of sources to such arrays. Plastid also includes numerous tools to manipulate even discontinuous genomic features, such as spliced transcripts, with nucleotide precision. Plastid automatically handles conversion between genomic and feature-centric coordinates, accounting for splicing and strand, freeing users of burdensome accounting. Finally, Plastid's data models use consistent and familiar biological idioms, enabling even beginners to develop sophisticated analytical workflows with minimal effort. Plastid is a versatile toolkit that has been used to analyze data from multiple NGS assays, including RNA-seq, ribosome profiling, and DMS-seq. It forms the genomic engine of our ORF annotation tool, ORF-RATER, and is readily

High-resolution geophysical profiling using a stepped-frequency ground penetrating radar

Energy Technology Data Exchange (ETDEWEB)

Noon, D; Longstaff, D [The University of Queensland, (Australia)

1996-05-01

This paper describes the results of a ground penetrating radar (GPR) system which uses stepped-frequency waveforms to obtain high-resolution geophysical profiles. The main application for this system is the high-resolution mapping of thin coal seam structures, in order to assist surface mining operations in open-cut coal mines. The required depth of penetration is one meter which represents the maximum thickness of coal seams that are designated `thin`. A resolution of five centimeters is required to resolve the minimum thickness of coal (or shale partings) which can be economically recovered in an open-cut coal mine. For this application, a stepped-frequency GPR system has been developed, because of its ultrawide bandwidth (1 to 2 GHz) and high external loop sensitivity (155 dB). The field test results of the stepped-frequency GPR system on a concrete pavement and at two Australian open-cut coal mines are also presented. 7 refs., 5 figs.

High resolution measurement of the velocity profiles of channel flows using the particle image velocimetry technique

International Nuclear Information System (INIS)

Nor Azizi Mohamed

2000-01-01

The high resolution velocity profiles of a uniform steady channel flow and a flow beneath waves were obtained using the particle image velocimetry (PIV) technique. The velocity profiles for each flow were calculated for both components. It is shown that the profiles obtained are very precise, displaying the point velocities from a few millimeters from the bottom of the channel up to the water surface across the water depth. In the case of the wave-induced flow, the profiles are shown under the respective wave phases and given in a plane representation. High resolution measurement of point velocities in a flow is achievable using PIV and invaluable when applied to a complex flow. (Author)

High-resolution mutational profiling suggests the genetic validity of glioblastoma patient-derived pre-clinical models.

Directory of Open Access Journals (Sweden)

Shawn E Yost

Full Text Available Recent advances in the ability to efficiently characterize tumor genomes is enabling targeted drug development, which requires rigorous biomarker-based patient selection to increase effectiveness. Consequently, representative DNA biomarkers become equally important in pre-clinical studies. However, it is still unclear how well these markers are maintained between the primary tumor and the patient-derived tumor models. Here, we report the comprehensive identification of somatic coding mutations and copy number aberrations in four glioblastoma (GBM primary tumors and their matched pre-clinical models: serum-free neurospheres, adherent cell cultures, and mouse xenografts. We developed innovative methods to improve the data quality and allow a strict comparison of matched tumor samples. Our analysis identifies known GBM mutations altering PTEN and TP53 genes, and new actionable mutations such as the loss of PIK3R1, and reveals clear patient-to-patient differences. In contrast, for each patient, we do not observe any significant remodeling of the mutational profile between primary to model tumors and the few discrepancies can be attributed to stochastic errors or differences in sample purity. Similarly, we observe ∼96% primary-to-model concordance in copy number calls in the high-cellularity samples. In contrast to previous reports based on gene expression profiles, we do not observe significant differences at the DNA level between in vitro compared to in vivo models. This study suggests, at a remarkable resolution, the genome-wide conservation of a patient's tumor genetics in various pre-clinical models, and therefore supports their use for the development and testing of personalized targeted therapies.

High-resolution humidity profiles retrieved from wind profiler radar measurements

Science.gov (United States)

Saïd, Frédérique; Campistron, Bernard; Di Girolamo, Paolo

2018-03-01

The retrieval of humidity profiles from wind profiler radars has already been documented in the past 30 years and is known to be neither as straightforward and nor as robust as the retrieval of the wind velocity. The main constraint to retrieve the humidity profile is the necessity to combine measurements from the wind profiler and additional measurements (such as observations from radiosoundings at a coarser time resolution). Furthermore, the method relies on some assumptions and simplifications that restrict the scope of its application. The first objective of this paper is to identify the obstacles and limitations and solve them, or at least define the field of applicability. To improve the method, we propose using the radar capacity to detect transition levels, such as the top level of the boundary layer, marked by a maximum in the radar reflectivity. This forces the humidity profile from the free troposphere and from the boundary layer to coincide at this level, after an optimization of the calibration coefficients, and reduces the error. The resulting mean bias affecting the specific humidity profile never exceeds 0.25 g kg-1. The second objective is to explore the capability of the algorithm to retrieve the humidity vertical profiles for an operational purpose by comparing the results with observations from a Raman lidar.

A high resolution beam profile monitor using Bremsstrahlung

International Nuclear Information System (INIS)

Norem, J.

1988-01-01

The development of efficient high energy linear colliders in the 1 TeV range requires final focus systems capable of producing beam spot sizes on the order of 1--20 nm, about three orders of magnitude smaller than those produced at the SLC. Although beam line designs exist which can, in principle, produce the required optics, the construction of quadrupoles with the size and precision required will be challenging. Field errors in these quads must be small and should be verified experimentally, which is difficult with existing technology. This paper describes a proposal to use bremsstrahlung from heavy targets to measure high energy beam profiles and positions with a resolution approaching a few nm. The method is also applicable to tests of other final focus systems (flat beams, plasma lenses) at lower energies. 6 refs., 3 figs., 1 tab

SIGMA: A System for Integrative Genomic Microarray Analysis of Cancer Genomes

Directory of Open Access Journals (Sweden)

Davies Jonathan J

2006-12-01

Full Text Available Abstract Background The prevalence of high resolution profiling of genomes has created a need for the integrative analysis of information generated from multiple methodologies and platforms. Although the majority of data in the public domain are gene expression profiles, and expression analysis software are available, the increase of array CGH studies has enabled integration of high throughput genomic and gene expression datasets. However, tools for direct mining and analysis of array CGH data are limited. Hence, there is a great need for analytical and display software tailored to cross platform integrative analysis of cancer genomes. Results We have created a user-friendly java application to facilitate sophisticated visualization and analysis such as cross-tumor and cross-platform comparisons. To demonstrate the utility of this software, we assembled array CGH data representing Affymetrix SNP chip, Stanford cDNA arrays and whole genome tiling path array platforms for cross comparison. This cancer genome database contains 267 profiles from commonly used cancer cell lines representing 14 different tissue types. Conclusion In this study we have developed an application for the visualization and analysis of data from high resolution array CGH platforms that can be adapted for analysis of multiple types of high throughput genomic datasets. Furthermore, we invite researchers using array CGH technology to deposit both their raw and processed data, as this will be a continually expanding database of cancer genomes. This publicly available resource, the System for Integrative Genomic Microarray Analysis (SIGMA of cancer genomes, can be accessed at http://sigma.bccrc.ca.

Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

International Nuclear Information System (INIS)

Carneiro, Ana; Isinger, Anna; Karlsson, Anna; Johansson, Jan; Jönsson, Göran; Bendahl, Pär-Ola; Falkenback, Dan; Halvarsson, Britta; Nilbert, Mef

2008-01-01

Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC

Genome-wide SNP discovery in tetraploid alfalfa using 454 sequencing and high resolution melting analysis

Directory of Open Access Journals (Sweden)

Zhao Patrick X

2011-07-01

Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most common type of sequence variation among plants and are often functionally important. We describe the use of 454 technology and high resolution melting analysis (HRM for high throughput SNP discovery in tetraploid alfalfa (Medicago sativa L., a species with high economic value but limited genomic resources. Results The alfalfa genotypes selected from M. sativa subsp. sativa var. 'Chilean' and M. sativa subsp. falcata var. 'Wisfal', which differ in water stress sensitivity, were used to prepare cDNA from tissue of clonally-propagated plants grown under either well-watered or water-stressed conditions, and then pooled for 454 sequencing. Based on 125.2 Mb of raw sequence, a total of 54,216 unique sequences were obtained including 24,144 tentative consensus (TCs sequences and 30,072 singletons, ranging from 100 bp to 6,662 bp in length, with an average length of 541 bp. We identified 40,661 candidate SNPs distributed throughout the genome. A sample of candidate SNPs were evaluated and validated using high resolution melting (HRM analysis. A total of 3,491 TCs harboring 20,270 candidate SNPs were located on the M. truncatula (MT 3.5.1 chromosomes. Gene Ontology assignments indicate that sequences obtained cover a broad range of GO categories. Conclusions We describe an efficient method to identify thousands of SNPs distributed throughout the alfalfa genome covering a broad range of GO categories. Validated SNPs represent valuable molecular marker resources that can be used to enhance marker density in linkage maps, identify potential factors involved in heterosis and genetic variation, and as tools for association mapping and genomic selection in alfalfa.

Genetic profiles of gastroesophageal cancer: combined analysis using expression array and tiling array--comparative genomic hybridization

DEFF Research Database (Denmark)

Isinger-Ekstrand, Anna; Johansson, Jan; Ohlsson, Mattias

2010-01-01

15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction, with upregulation in one quarter of the tumors. Gains......We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high......-resolution array-based comparative genomic hybridization and 27k oligo gene expression arrays, and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-23, 5p...

A High Resolution Genetic Map Anchoring Scaffolds of the Sequenced Watermelon Genome

Science.gov (United States)

Kou, Qinghe; Jiang, Jiao; Guo, Shaogui; Zhang, Haiying; Hou, Wenju; Zou, Xiaohua; Sun, Honghe; Gong, Guoyi; Levi, Amnon; Xu, Yong

2012-01-01

As part of our ongoing efforts to sequence and map the watermelon (Citrullus spp.) genome, we have constructed a high density genetic linkage map. The map positioned 234 watermelon genome sequence scaffolds (an average size of 1.41 Mb) that cover about 330 Mb and account for 93.5% of the 353 Mb of the assembled genomic sequences of the elite Chinese watermelon line 97103 (Citrullus lanatus var. lanatus). The genetic map was constructed using an F8 population of 103 recombinant inbred lines (RILs). The RILs are derived from a cross between the line 97103 and the United States Plant Introduction (PI) 296341-FR (C. lanatus var. citroides) that contains resistance to fusarium wilt (races 0, 1, and 2). The genetic map consists of eleven linkage groups that include 698 simple sequence repeat (SSR), 219 insertion-deletion (InDel) and 36 structure variation (SV) markers and spans ∼800 cM with a mean marker interval of 0.8 cM. Using fluorescent in situ hybridization (FISH) with 11 BACs that produced chromosome-specifc signals, we have depicted watermelon chromosomes that correspond to the eleven linkage groups constructed in this study. The high resolution genetic map developed here should be a useful platform for the assembly of the watermelon genome, for the development of sequence-based markers used in breeding programs, and for the identification of genes associated with important agricultural traits. PMID:22247776

High-resolution altitude profiles of the atmospheric turbulence with PML at the Sutherland Observatory

Science.gov (United States)

Catala, L.; Ziad, A.; Fanteï-Caujolle, Y.; Crawford, S. M.; Buckley, D. A. H.; Borgnino, J.; Blary, F.; Nickola, M.; Pickering, T.

2017-05-01

With the prospect of the next generation of ground-based telescopes, the extremely large telescopes, increasingly complex and demanding adaptive optics systems are needed. This is to compensate for image distortion caused by atmospheric turbulence and fully take advantage of mirrors with diameters of 30-40 m. This requires a more precise characterization of the turbulence. The Profiler of Moon Limb (PML) was developed within this context. The PML aims to provide high-resolution altitude profiles of the turbulence using differential measurements of the Moon limb position to calculate the transverse spatio-angular covariance of the angle of arrival fluctuations. The covariance of differential image motion for different separation angles is sensitive to the altitude distribution of the seeing. The use of the continuous Moon limb provides a large number of separation angles allowing for the high-resolution altitude of the profiles. The method is presented and tested with simulated data. Moreover, a PML instrument was deployed at the Sutherland Observatory in South Africa in 2011 August. We present here the results of this measurement campaign.

Triple aldose reductase/α-glucosidase/radical scavenging high-resolution profiling combined with high-performance liquid chromatography – high-resolution mass spectrometry – solid-phase extraction – nuclear magnetic resonance spectroscopy for identification of antidiabetic constituents in crude, extract of Radix Scutellariae

DEFF Research Database (Denmark)

Tahtah, Yousof; Kongstad, Kenneth Thermann; Wubshet, Sileshi Gizachew

2015-01-01

high-performance liquid chromatography – high-resolution mass spectrometry – solid-phase extraction – nuclear magnetic resonance spectroscopy. The only α-glucosidase inhibitor was baicalein, whereas main aldose reductase inhibitors in the crude extract were baicalein and skullcapflavone II, and main....../α-glucosidase/radical scavenging high-resolution inhibition profile - allowing proof of concept with Radix Scutellariae crude extract as a polypharmacological herbal drug. The triple bioactivity high-resolution profiles were used to pinpoint bioactive compounds, and subsequent structure elucidation was performed with hyphenated...

Development of a procedure to model high-resolution wind profiles from smoothed or low-frequency data

Science.gov (United States)

Camp, D. W.

1977-01-01

The derivation of simulated Jimsphere wind profiles from low-frequency rawinsonde data and a generated set of white noise data are presented. A computer program is developed to model high-resolution wind profiles based on the statistical properties of data from the Kennedy Space Center, Florida. Comparison of the measured Jimsphere data, rawinsonde data, and the simulated profiles shows excellent agreement.

High-resolution velocimetry in energetic tidal currents using a convergent-beam acoustic Doppler profiler

Science.gov (United States)

Sellar, Brian; Harding, Samuel; Richmond, Marshall

2015-08-01

An array of single-beam acoustic Doppler profilers has been developed for the high resolution measurement of three-dimensional tidal flow velocities and subsequently tested in an energetic tidal site. This configuration has been developed to increase spatial resolution of velocity measurements in comparison to conventional acoustic Doppler profilers (ADPs) which characteristically use divergent acoustic beams emanating from a single instrument. This is achieved using geometrically convergent acoustic beams creating a sample volume at the focal point of 0.03 m3. Away from the focal point, the array is also able to simultaneously reconstruct three-dimensional velocity components in a profile throughout the water column, and is referred to herein as a convergent-beam acoustic Doppler profiler (C-ADP). Mid-depth profiling is achieved through integration of the sensor platform with the operational commercial-scale Alstom 1 MW DeepGen-IV Tidal Turbine deployed at the European Marine Energy Center, Orkney Isles, UK. This proof-of-concept paper outlines the C-ADP system configuration and comparison to measurements provided by co-installed reference instrumentation. Comparison of C-ADP to standard divergent ADP (D-ADP) velocity measurements reveals a mean difference of 8 mm s-1, standard deviation of 18 mm s-1, and an order of magnitude reduction in realisable length scale. C-ADP focal point measurements compared to a proximal single-beam reference show peak cross-correlation coefficient of 0.96 over 4.0 s averaging period and a 47% reduction in Doppler noise. The dual functionality of the C-ADP as a profiling instrument with a high resolution focal point make this configuration a unique and valuable advancement in underwater velocimetry enabling improved quantification of flow turbulence. Since waves are simultaneously measured via profiled velocities, pressure measurements and surface detection, it is expected that derivatives of this system will be a powerful tool in

Genomic characterization of recurrent high-grade astroblastoma.

Science.gov (United States)

Bale, Tejus A; Abedalthagafi, Malak; Bi, Wenya Linda; Kang, Yun Jee; Merrill, Parker; Dunn, Ian F; Dubuc, Adrian; Charbonneau, Sarah K; Brown, Loreal; Ligon, Azra H; Ramkissoon, Shakti H; Ligon, Keith L

2016-01-01

Astroblastomas are rare primary brain tumors, diagnosed based on histologic features. Not currently assigned a WHO grade, they typically display indolent behavior, with occasional variants taking a more aggressive course. We characterized the immunohistochemical characteristics, copy number (high-resolution array comparative genomic hybridization, OncoCopy) and mutational profile (targeted next-generation exome sequencing, OncoPanel) of a cohort of seven biopsies from four patients to identify recurrent genomic events that may help distinguish astroblastomas from other more common high-grade gliomas. We found that tumor histology was variable across patients and between primary and recurrent tumor samples. No common molecular features were identified among the four tumors. Mutations commonly observed in astrocytic tumors (IDH1/2, TP53, ATRX, and PTEN) or ependymoma were not identified. However one case with rapid clinical progression displayed mutations more commonly associated with GBM (NF1(N1054H/K63)*, PIK3CA(R38H) and ERG(A403T)). Conversely, another case, originally classified as glioblastoma with nine-year survival before recurrence, lacked a GBM mutational profile. Other mutations frequently seen in lower grade gliomas (BCOR, BCORL1, ERBB3, MYB, ATM) were also present in several tumors. Copy number changes were variable across tumors. Our findings indicate that astroblastomas have variable growth patterns and morphologic features, posing significant challenges to accurate classification in the absence of diagnostically specific copy number alterations and molecular features. Their histopathologic overlap with glioblastoma will likely confound the observation of long-term GBM "survivors". Further genomic profiling is needed to determine whether these tumors represent a distinct entity and to guide management strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Longitudinal profile diagnostic scheme with subfemtosecond resolution for high-brightness electron beams

Directory of Open Access Journals (Sweden)

G. Andonian

2011-07-01

Full Text Available High-resolution measurement of the longitudinal profile of a relativistic electron beam is of utmost importance for linac based free-electron lasers and other advanced accelerator facilities that employ ultrashort bunches. In this paper, we investigate a novel scheme to measure ultrashort bunches (subpicosecond with exceptional temporal resolution (hundreds of attoseconds and dynamic range. The scheme employs two orthogonally oriented deflecting sections. The first imparts a short-wavelength (fast temporal resolution horizontal angular modulation on the beam, while the second imparts a long-wavelength (slow angular kick in the vertical dimension. Both modulations are observable on a standard downstream screen in the form of a streaked sinusoidal beam structure. We demonstrate, using scaled variables in a quasi-1D approximation, an expression for the temporal resolution of the scheme and apply it to a proof-of-concept experiment at the UCLA Neptune high-brightness injector facility. The scheme is also investigated for application at the SLAC NLCTA facility, where we show that the subfemtosecond resolution is sufficient to resolve the temporal structure of the beam used in the echo-enabled free-electron laser. We employ beam simulations to verify the effect for typical Neptune and NLCTA parameter sets and demonstrate the feasibility of the concept.

Development of a High Resolution Virulence Allelic Profiling (HReVAP) Approach Based on the Accessory Genome of Escherichia coli to Characterize Shiga-Toxin Producing E. coli (STEC)

Science.gov (United States)

Michelacci, Valeria; Orsini, Massimiliano; Knijn, Arnold; Delannoy, Sabine; Fach, Patrick; Caprioli, Alfredo; Morabito, Stefano

2016-01-01

Shiga-toxin producing Escherichia coli (STEC) strains possess a large accessory genome composed of virulence genes existing in multiple allelic variants, which sometimes segregate with specific STEC subpopulations. We analyzed the allelic variability of 91 virulence genes of STEC by Real Time PCR followed by melting curves analysis in 713 E. coli strains including 358 STEC. The 91 genes investigated were located on the locus of enterocyte effacement (LEE), OI-57, and OI-122 pathogenicity islands and displayed a total of 476 alleles in the study population. The combinations of the 91 alleles of each strain were termed allelic signatures and used to perform cluster analyses. We termed such an approach High Resolution Virulence Allelic Profiling (HReVAP) and used it to investigate the phylogeny of STEC of multiple serogroups. The dendrograms obtained identified groups of STEC segregating approximately with the serogroups and allowed the identification of subpopulations within the single groups. The study of the allelic signatures provided further evidence of the coevolution of the LEE and OI-122, reflecting the occurrence of their acquisition through a single event. The HReVAP analysis represents a sensitive tool for studying the evolution of LEE-positive STEC. PMID:26941726

Combined Atmospheric and Ocean Profiling from an Airborne High Spectral Resolution Lidar

Directory of Open Access Journals (Sweden)

Hair Johnathan

2016-01-01

Full Text Available First of its kind combined atmospheric and ocean profile data were collected by the recently upgraded NASA Langley Research Center’s (LaRC High Spectral Resolution Lidar (HSRL-1 during the 17 July – 7 August 2014 Ship-Aircraft Bio-Optical Research Experiment (SABOR. This mission sampled over a region that covered the Gulf of Maine, open-ocean near Bermuda, and coastal waters from Virginia to Rhode Island. The HSRL-1 and the Research Scanning Polarimeter from NASA Goddard Institute for Space Studies collected data onboard the NASA LaRC King Air aircraft and flight operations were closely coordinated with the Research Vessel Endeavor that made in situ ocean optical measurements. The lidar measurements provided profiles of atmospheric backscatter and particulate depolarization at 532nm, 1064nm, and extinction (532nm from approximately 9km altitude. In addition, for the first time HSRL seawater backscatter, depolarization, and diffuse attenuation data at 532nm were collected and compared to both the ship measurements and the Moderate Resolution Imaging Spectrometer (NASA MODIS-Aqua satellite ocean retrievals.

Genome-wide dynamic transcriptional profiling in clostridium beijerinckii NCIMB 8052 using single-nucleotide resolution RNA-Seq

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Wang Yi

2012-03-01

Full Text Available Abstract Background Clostridium beijerinckii is a prominent solvent-producing microbe that has great potential for biofuel and chemical industries. Although transcriptional analysis is essential to understand gene functions and regulation and thus elucidate proper strategies for further strain improvement, limited information is available on the genome-wide transcriptional analysis for C. beijerinckii. Results The genome-wide transcriptional dynamics of C. beijerinckii NCIMB 8052 over a batch fermentation process was investigated using high-throughput RNA-Seq technology. The gene expression profiles indicated that the glycolysis genes were highly expressed throughout the fermentation, with comparatively more active expression during acidogenesis phase. The expression of acid formation genes was down-regulated at the onset of solvent formation, in accordance with the metabolic pathway shift from acidogenesis to solventogenesis. The acetone formation gene (adc, as a part of the sol operon, exhibited highly-coordinated expression with the other sol genes. Out of the > 20 genes encoding alcohol dehydrogenase in C. beijerinckii, Cbei_1722 and Cbei_2181 were highly up-regulated at the onset of solventogenesis, corresponding to their key roles in primary alcohol production. Most sporulation genes in C. beijerinckii 8052 demonstrated similar temporal expression patterns to those observed in B. subtilis and C. acetobutylicum, while sporulation sigma factor genes sigE and sigG exhibited accelerated and stronger expression in C. beijerinckii 8052, which is consistent with the more rapid forespore and endspore development in this strain. Global expression patterns for specific gene functional classes were examined using self-organizing map analysis. The genes associated with specific functional classes demonstrated global expression profiles corresponding to the cell physiological variation and metabolic pathway switch. Conclusions The results from this

Comparative Proteomic Profile of the Human Umbilical Cord Blood Exosomes between Normal and Preeclampsia Pregnancies with High-Resolution Mass Spectrometry

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Ruizhe Jia

2015-07-01

Full Text Available Background/Aims: Exosomes are extracellular vesicles that are involved in several biological processes. The roles of proteins from human umbilical cord blood exosomes in the pathogenesis of preeclampsia remains poorly understood. Methods: In this study, we used high-resolution LC-MS/MS technologies to construct a comparative proteomic profiling of human umbilical cord blood exosomes between normal and preeclamptic pregnancies. Results: A total of 221 proteins were detected in human umbilical cord blood exosomes, with 14 upregulated and 15 downregulated proteins were definitively identified between preeclamptic and control pregnancies. Further bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these differentially expressed proteins correlate with enzyme regulator activity, binding, extracellular region, cell part, biological regulation, cellular process and complement and coagulation cascades occurring during pathological changes of preeclampsia. Conclusion: Our results show significantly altered expression profiles of proteins in human umbilical cord blood exosomes between normal and preeclampsia pregnancies. These proteins may be involved in the etiology of preeclampsia.

High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling.

Science.gov (United States)

Irigoyen, Nerea; Firth, Andrew E; Jones, Joshua D; Chung, Betty Y-W; Siddell, Stuart G; Brierley, Ian

2016-02-01

Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global "snap-shot" of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal

High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling.

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Nerea Irigoyen

2016-02-01

Full Text Available Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV, are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global "snap-shot" of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59, a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the

Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma.

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David Lindgren

Full Text Available Similar to other malignancies, urothelial carcinoma (UC is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21, and BCL2L1 (20q11. We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development.

Heat Transport upon River-Water Infiltration investigated by Fiber-Optic High-Resolution Temperature Profiling

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Vogt, T.; Schirmer, M.; Cirpka, O. A.

2010-12-01

Infiltrating river water is of high relevance for drinking water supply by river bank filtration as well as for riparian groundwater ecology. Quantifying flow patterns and velocities, however, is hampered by temporal and spatial variations of exchange fluxes. In recent years, heat has become a popular natural tracer to estimate exchange rates between rivers and groundwater. Nevertheless, field investigations are often limited by insufficient sensors spacing or simplifying assumptions such as one-dimensional flow. Our interest lies in a detailed local survey of river water infiltration at a restored river section at the losing river Thur in northeast Switzerland. Here, we measured three high-resolution temperature profiles along an assumed flow path by means of distributed temperature sensing (DTS) using fiber optic cables wrapped around poles. Moreover, piezometers were equipped with standard temperature sensors for a comparison to the DTS data. Diurnal temperature oscillations were tracked in the river bed and the riparian groundwater and analyzed by means of dynamic harmonic regression and subsequent modeling of heat transport with sinusoidal boundary conditions to quantify seepage velocities and thermal diffusivities. Compared to the standard temperature sensors, the DTS data give a higher vertical resolution, facilitating the detection of process- and structure-dependent patterns of the spatiotemporal temperature field. This advantage overcompensates the scatter in the data due to instrument noise. In particular, we could demonstrate the impact of heat conduction through the unsaturated zone on the riparian groundwater by the high resolution temperature profiles.

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

OpenAIRE

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

2012-01-01

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it possible to map SCEs at orders-of-magnitude greater resolution than was previously possible. On average, murine embryonic stem (mES) cells exhibit eight SCEs, which are detected at a resolution of up...

Targeting high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance analysis with high-resolution radical scavenging profiles - bioactive secondary metabolites from the endophytic fungus Penicillium namyslowskii

DEFF Research Database (Denmark)

Wubshet, Sileshi Gizachew; Nyberg, Nils; Tejesvi, Mysore V.

2013-01-01

The high-resolution radical scavenging profile of an extract of the endophytic fungus Penicillium namyslowskii was used to target analysis by high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HPLC...... NMR probe designed for 1.7-mm NMR tubes. To further explore the potential of the above HPLC-HRMS-SPE-NMR platform for analysis of endophytic extracts, six peaks displaying no radical scavenging activity were also analyzed. This allowed unambiguous identification of six metabolites, i...... and griseofulvin, directly from crude extract via HPLC-HRMS-SPE-NMR. Dechlorodehydrogriseofulvin was reported for the first time from nature....

Ground-based lidar and microwave radiometry synergy for high vertical resolution absolute humidity profiling

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Barrera-Verdejo, María; Crewell, Susanne; Löhnert, Ulrich; Orlandi, Emiliano; Di Girolamo, Paolo

2016-08-01

Continuous monitoring of atmospheric humidity profiles is important for many applications, e.g., assessment of atmospheric stability and cloud formation. Nowadays there are a wide variety of ground-based sensors for atmospheric humidity profiling. Unfortunately there is no single instrument able to provide a measurement with complete vertical coverage, high vertical and temporal resolution and good performance under all weather conditions, simultaneously. For example, Raman lidar (RL) measurements can provide water vapor with a high vertical resolution, albeit with limited vertical coverage, due to sunlight contamination and the presence of clouds. Microwave radiometers (MWRs) receive water vapor information throughout the troposphere, though their vertical resolution is poor. In this work, we present an MWR and RL system synergy, which aims to overcome the specific sensor limitations. The retrieval algorithm combining these two instruments is an optimal estimation method (OEM), which allows for an uncertainty analysis of the retrieved profiles. The OEM combines measurements and a priori information, taking the uncertainty of both into account. The measurement vector consists of a set of MWR brightness temperatures and RL water vapor profiles. The method is applied to a 2-month field campaign around Jülich (Germany), focusing on clear sky periods. Different experiments are performed to analyze the improvements achieved via the synergy compared to the individual retrievals. When applying the combined retrieval, on average the theoretically determined absolute humidity uncertainty is reduced above the last usable lidar range by a factor of ˜ 2 with respect to the case where only RL measurements are used. The analysis in terms of degrees of freedom per signal reveal that most information is gained above the usable lidar range, especially important during daytime when the lidar vertical coverage is limited. The retrieved profiles are further evaluated using

Analysis of Chinese women with primary ovarian insufficiency by high resolution array-comparative genomic hybridization.

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Liao, Can; Fu, Fang; Yang, Xin; Sun, Yi-Min; Li, Dong-Zhi

2011-06-01

Primary ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 years. The etiology of primary ovarian insufficiency in human female patients is still unclear. The purpose of this study is to investigate the potential genetic causes in primary amenorrhea patients by high resolution array based comparative genomic hybridization (array-CGH) analysis. Following the standard karyotyping analysis, genomic DNA from whole blood of 15 primary amenorrhea patients and 15 normal control women was hybridized with Affymetrix cytogenetic 2.7M arrays following the standard protocol. Copy number variations identified by array-CGH were confirmed by real time polymerase chain reaction. All the 30 samples were negative by conventional karyotyping analysis. Microdeletions on chromosome 17q21.31-q21.32 with approximately 1.3 Mb were identified in four patients by high resolution array-CGH analysis. This included the female reproductive secretory pathway related factor N-ethylmaleimide-sensitive factor (NSF) gene. The results of the present study suggest that there may be critical regions regulating primary ovarian insufficiency in women with a 17q21.31-q21.32 microdeletion. This effect might be due to the loss of function of the NSF gene/genes within the deleted region or to effects on contiguous genes.

Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures.

Science.gov (United States)

Johnson, Adrienne; Severson, Eric; Gay, Laurie; Vergilio, Jo-Anne; Elvin, Julia; Suh, James; Daniel, Sugganth; Covert, Mandy; Frampton, Garrett M; Hsu, Sigmund; Lesser, Glenn J; Stogner-Underwood, Kimberly; Mott, Ryan T; Rush, Sarah Z; Stanke, Jennifer J; Dahiya, Sonika; Sun, James; Reddy, Prasanth; Chalmers, Zachary R; Erlich, Rachel; Chudnovsky, Yakov; Fabrizio, David; Schrock, Alexa B; Ali, Siraj; Miller, Vincent; Stephens, Philip J; Ross, Jeffrey; Crawford, John R; Ramkissoon, Shakti H

2017-12-01

Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb]). In pLGGs, we detected genomic alterations (GA) in 95.2% (119/125) of tumors. BRAF was most frequently altered (48%; 60/125), and FGFR1 missense (17.6%; 22/125), NF1 loss of function (8.8%; 11/125), and TP53 (5.6%; 7/125) mutations were also detected. Rearrangements were identified in 35% of pLGGs, including KIAA1549-BRAF , QKI-RAF1 , FGFR3-TACC3 , CEP85L-ROS1 , and GOPC-ROS1 fusions. Among pHGGs, GA were identified in 96.8% (152/157). The genes most frequently mutated were TP53 (49%; 77/157), H3F3A (37.6%; 59/157), ATRX (24.2%; 38/157), NF1 (22.2%; 35/157), and PDGFRA (21.7%; 34/157). Interestingly, most H3F3A mutations (81.4%; 35/43) were the variant K28M. Midline tumor analysis revealed H3F3A mutations (40%; 40/100) consisted solely of the K28M variant. Pediatric high-grade gliomas harbored oncogenic EML4-ALK , DGKB-ETV1 , ATG7-RAF1 , and EWSR1-PATZ1 fusions. Six percent (9/157) of pHGGs were hypermutated (TMB >20 mutations per Mb; range 43-581 mutations per Mb), harboring mutations deleterious for DNA repair in MSH6, MSH2, MLH1, PMS2, POLE , and POLD1 genes (78% of cases). Comprehensive genomic profiling of pediatric gliomas provides objective data that promote diagnostic accuracy and enhance clinical decision-making. Additionally, TMB could be a biomarker to identify pediatric glioblastoma (GBM) patients who may benefit from immunotherapy. By providing objective data to support diagnostic, prognostic, and therapeutic decision-making, comprehensive genomic profiling is necessary for

Genome-wide high-resolution mapping of UV-induced mitotic recombination events in Saccharomyces cerevisiae.

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Yi Yin

2013-10-01

Full Text Available In the yeast Saccharomyces cerevisiae and most other eukaryotes, mitotic recombination is important for the repair of double-stranded DNA breaks (DSBs. Mitotic recombination between homologous chromosomes can result in loss of heterozygosity (LOH. In this study, LOH events induced by ultraviolet (UV light are mapped throughout the genome to a resolution of about 1 kb using single-nucleotide polymorphism (SNP microarrays. UV doses that have little effect on the viability of diploid cells stimulate crossovers more than 1000-fold in wild-type cells. In addition, UV stimulates recombination in G1-synchronized cells about 10-fold more efficiently than in G2-synchronized cells. Importantly, at high doses of UV, most conversion events reflect the repair of two sister chromatids that are broken at approximately the same position whereas at low doses, most conversion events reflect the repair of a single broken chromatid. Genome-wide mapping of about 380 unselected crossovers, break-induced replication (BIR events, and gene conversions shows that UV-induced recombination events occur throughout the genome without pronounced hotspots, although the ribosomal RNA gene cluster has a significantly lower frequency of crossovers.

Three gangliogliomas: results of GTG-banding, SKY, genome-wide high resolution SNP-array, gene expression and review of the literature.

Science.gov (United States)

Xu, Li-Xin; Holland, Heidrun; Kirsten, Holger; Ahnert, Peter; Krupp, Wolfgang; Bauer, Manfred; Schober, Ralf; Mueller, Wolf; Fritzsch, Dominik; Meixensberger, Jürgen; Koschny, Ronald

2015-04-01

According to the World Health Organization gangliogliomas are classified as well-differentiated and slowly growing neuroepithelial tumors, composed of neoplastic mature ganglion and glial cells. It is the most frequent tumor entity observed in patients with long-term epilepsy. Comprehensive cytogenetic and molecular cytogenetic data including high-resolution genomic profiling (single nucleotide polymorphism (SNP)-array) of gangliogliomas are scarce but necessary for a better oncological understanding of this tumor entity. For a detailed characterization at the single cell and cell population levels, we analyzed genomic alterations of three gangliogliomas using trypsin-Giemsa banding (GTG-banding) and by spectral karyotyping (SKY) in combination with SNP-array and gene expression array experiments. By GTG and SKY, we could confirm frequently detected chromosomal aberrations (losses within chromosomes 10, 13 and 22; gains within chromosomes 5, 7, 8 and 12), and identify so far unknown genetic aberrations like the unbalanced non-reciprocal translocation t(1;18)(q21;q21). Interestingly, we report on the second so far detected ganglioglioma with ring chromosome 1. Analyses of SNP-array data from two of the tumors and respective germline DNA (peripheral blood) identified few small gains and losses and a number of copy-neutral regions with loss of heterozygosity (LOH) in germline and in tumor tissue. In comparison to germline DNA, tumor tissues did not show substantial regions with significant loss or gain or with newly developed LOH. Gene expression analyses of tumor-specific genes revealed similarities in the profile of the analyzed samples regarding different relevant pathways. Taken together, we describe overlapping but also distinct and novel genetic aberrations of three gangliogliomas. © 2014 Japanese Society of Neuropathology.

Application of high-resolution domestic electricity load profiles in network modelling

DEFF Research Database (Denmark)

Marszal, Anna Joanna; Mendaza, Iker Diaz de Cerio; Heiselberg, Per Kvols

2016-01-01

the generated profiles are inputted in a low-voltage network model created in DIgSILENT PowerFactory. By means of employing 1 hour based demand and generation profiles in during dynamic studies, the representation of the local power system performance might sometimes not be as accurate as needed. In the test...... with modeling when 1-minute domestic electricity demand and generation profiles are used as inputs. The analysis is done with a case study of low-voltage network located in Northern Denmark. The analysis includes two parts. The first part focuses on modeling the domestic demands and on-site generation in 1......-minute resolution. The load profiles of the household appliances are created using a bottom-up model, which uses the 1-minute cycle power use characteristics of a single appliance as the main building block. The profiles of heavy electric appliances, such as heat pump, are not included in the above...

A high resolution atlas of Mg II profiles

Science.gov (United States)

Ewald, R.; Nichols-Bohlin, Joy Y.; Kondo, Yoji

1990-01-01

An atlas of high dispersion Mg II profiles for standard stars of spectral types B0 through G9 is presented. The atlas contains plots of the Mg II profiles for approximately 65 stars and associated equivalent width measurements for both absorption and emission components, and the subordinate lines. The atlas is used to investigate systematic behavior of the Mg II profiles and correlation of the behavior with spectral classification.

Salmonella enterica Prophage Sequence Profiles Reflect Genome Diversity and Can Be Used for High Discrimination Subtyping

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Walid Mottawea

2018-05-01

Full Text Available Non-typhoidal Salmonella is a leading cause of foodborne illness worldwide. Prompt and accurate identification of the sources of Salmonella responsible for disease outbreaks is crucial to minimize infections and eliminate ongoing sources of contamination. Current subtyping tools including single nucleotide polymorphism (SNP typing may be inadequate, in some instances, to provide the required discrimination among epidemiologically unrelated Salmonella strains. Prophage genes represent the majority of the accessory genes in bacteria genomes and have potential to be used as high discrimination markers in Salmonella. In this study, the prophage sequence diversity in different Salmonella serovars and genetically related strains was investigated. Using whole genome sequences of 1,760 isolates of S. enterica representing 151 Salmonella serovars and 66 closely related bacteria, prophage sequences were identified from assembled contigs using PHASTER. We detected 154 different prophages in S. enterica genomes. Prophage sequences were highly variable among S. enterica serovars with a median ± interquartile range (IQR of 5 ± 3 prophage regions per genome. While some prophage sequences were highly conserved among the strains of specific serovars, few regions were lineage specific. Therefore, strains belonging to each serovar could be clustered separately based on their prophage content. Analysis of S. Enteritidis isolates from seven outbreaks generated distinct prophage profiles for each outbreak. Taken altogether, the diversity of the prophage sequences correlates with genome diversity. Prophage repertoires provide an additional marker for differentiating S. enterica subtypes during foodborne outbreaks.

High-Resolution Genome-Wide Linkage Mapping Identifies Susceptibility Loci for BMI in the Chinese Population

DEFF Research Database (Denmark)

Zhang, Dong Feng; Pang, Zengchang; Li, Shuxia

2012-01-01

The genetic loci affecting the commonly used BMI have been intensively investigated using linkage approaches in multiple populations. This study aims at performing the first genome-wide linkage scan on BMI in the Chinese population in mainland China with hypothesis that heterogeneity in genetic...... linkage could exist in different ethnic populations. BMI was measured from 126 dizygotic twins in Qingdao municipality who were genotyped using high-resolution Affymetrix Genome-Wide Human SNP arrays containing about 1 million single-nucleotide polymorphisms (SNPs). Nonparametric linkage analysis...... in western countries. Multiple loci showing suggestive linkage were found on chromosome 1 (lod score 2.38 at 242 cM), chromosome 8 (2.48 at 95 cM), and chromosome 14 (2.2 at 89.4 cM). The strong linkage identified in the Chinese subjects that is consistent with that found in populations of European origin...

Targeted metabolite profile of food bioactive compounds by Orbitrap high resolution mass spectrometry: The 'FancyTiles' approach

NARCIS (Netherlands)

Troise, A.D.; Ferracane, R.; Palermo, M.; Fogliano, V.

2014-01-01

In this paper a new targeted metabolic profile approach using Orbitrap high resolution mass spectrometry was described. For each foodmatrix various classes of bioactive compounds and some specificmetabolites of interest were selected on the basis of the existing knowledge creating an easy-to-read

Hi-C 2.0: An optimized Hi-C procedure for high-resolution genome-wide mapping of chromosome conformation.

Science.gov (United States)

Belaghzal, Houda; Dekker, Job; Gibcus, Johan H

2017-07-01

Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (kb) resolution. It also includes steps to reduce random ligation and the generation of uninformative molecules, such as unligated ends, to improve the amount of valid intra-chromosomal read pairs. This protocol allows for obtaining information on conformational structures such as compartment and topologically associating domains, as well as high-resolution conformational features such as DNA loops. Copyright © 2017 Elsevier Inc. All rights reserved.

Quadruplex MAPH: improvement of throughput in high-resolution copy number screening.

Science.gov (United States)

Tyson, Jess; Majerus, Tamsin Mo; Walker, Susan; Armour, John Al

2009-09-28

Copy number variation (CNV) in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way. Multiplex Amplifiable Probe Hybridisation (MAPH) is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH") that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) samples. QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms.

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

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Chiao-Ling Lo

2016-08-01

Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

Science.gov (United States)

Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

2016-08-01

Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

Comprehensive evaluation of genome-wide 5-hydroxymethylcytosine profiling approaches in human DNA.

Science.gov (United States)

Skvortsova, Ksenia; Zotenko, Elena; Luu, Phuc-Loi; Gould, Cathryn M; Nair, Shalima S; Clark, Susan J; Stirzaker, Clare

2017-01-01

The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping the mammalian DNA methylation landscape. The gold-standard bisulphite conversion technologies to study DNA methylation do not distinguish between 5mC and 5hmC. However, new approaches to mapping 5hmC genome-wide have advanced rapidly, although it is unclear how the different methods compare in accurately calling 5hmC. In this study, we provide a comparative analysis on brain DNA using three 5hmC genome-wide approaches, namely whole-genome bisulphite/oxidative bisulphite sequencing (WG Bis/OxBis-seq), Infinium HumanMethylation450 BeadChip arrays coupled with oxidative bisulphite (HM450K Bis/OxBis) and antibody-based immunoprecipitation and sequencing of hydroxymethylated DNA (hMeDIP-seq). We also perform loci-specific TET-assisted bisulphite sequencing (TAB-seq) for validation of candidate regions. We show that whole-genome single-base resolution approaches are advantaged in providing precise 5hmC values but require high sequencing depth to accurately measure 5hmC, as this modification is commonly in low abundance in mammalian cells. HM450K arrays coupled with oxidative bisulphite provide a cost-effective representation of 5hmC distribution, at CpG sites with 5hmC levels >~10%. However, 5hmC analysis is restricted to the genomic location of the probes, which is an important consideration as 5hmC modification is commonly enriched at enhancer elements. Finally, we show that the widely used hMeDIP-seq method provides an efficient genome-wide profile of 5hmC and shows high correlation with WG Bis/OxBis-seq 5hmC distribution in brain DNA. However, in cell line DNA with low levels of 5hmC, hMeDIP-seq-enriched regions are not detected by WG Bis/OxBis or HM450K, either suggesting misinterpretation of 5hmC calls by hMeDIP or lack of sensitivity of the latter methods. We

Quadruplex MAPH: improvement of throughput in high-resolution copy number screening

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Walker Susan

2009-09-01

Full Text Available Abstract Background Copy number variation (CNV in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way. Results Multiplex Amplifiable Probe Hybridisation (MAPH is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH" that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC samples. Conclusion QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms.

Genomic profiling of CHEK2*1100delC-mutated breast carcinomas

International Nuclear Information System (INIS)

Massink, Maarten P. G.; Kooi, Irsan E.; Martens, John W. M.; Waisfisz, Quinten; Meijers-Heijboer, Hanne

2015-01-01

CHEK2*1100delC is a moderate-risk breast cancer susceptibility allele with a high prevalence in the Netherlands. We performed copy number and gene expression profiling to investigate whether CHEK2*1100delC breast cancers harbor characteristic genomic aberrations, as seen for BRCA1 mutated breast cancers. We performed high-resolution SNP array and gene expression profiling of 120 familial breast carcinomas selected from a larger cohort of 155 familial breast tumors, including BRCA1, BRCA2, and CHEK2 mutant tumors. Gene expression analyses based on a mRNA immune signature was used to identify samples with relative low amounts of tumor infiltrating lymphocytes (TILs), which were previously found to disturb tumor copy number and LOH (loss of heterozygosity) profiling. We specifically compared the genomic and gene expression profiles of CHEK2*1100delC breast cancers (n = 14) with BRCAX (familial non-BRCA1/BRCA2/CHEK2*1100delC mutated) breast cancers (n = 34) of the luminal intrinsic subtypes for which both SNP-array and gene expression data is available. High amounts of TILs were found in a relatively small number of luminal breast cancers as compared to breast cancers of the basal-like subtype. As expected, these samples mostly have very few copy number aberrations and no detectable regions of LOH. By unsupervised hierarchical clustering of copy number data we observed a great degree of heterogeneity amongst the CHEK2*1100delC breast cancers, comparable to the BRCAX breast cancers. Furthermore, copy number aberrations were mostly seen at low frequencies in both the CHEK2*1100delC and BRCAX group of breast cancers. However, supervised class comparison identified copy number loss of chromosomal arm 1p to be associated with CHEK2*1100delC status. In conclusion, in contrast to basal-like BRCA1 mutated breast cancers, no apparent specific somatic copy number aberration (CNA) profile for CHEK2*1100delC breast cancers was found. With the possible exception of copy number loss

A high-resolution whole-genome map of key chromatin modifications in the adult Drosophila melanogaster.

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Yin, Hang; Sweeney, Sarah; Raha, Debasish; Snyder, Michael; Lin, Haifan

2011-12-01

Epigenetic research has been focused on cell-type-specific regulation; less is known about common features of epigenetic programming shared by diverse cell types within an organism. Here, we report a modified method for chromatin immunoprecipitation and deep sequencing (ChIP-Seq) and its use to construct a high-resolution map of the Drosophila melanogaster key histone marks, heterochromatin protein 1a (HP1a) and RNA polymerase II (polII). These factors are mapped at 50-bp resolution genome-wide and at 5-bp resolution for regulatory sequences of genes, which reveals fundamental features of chromatin modification landscape shared by major adult Drosophila cell types: the enrichment of both heterochromatic and euchromatic marks in transposons and repetitive sequences, the accumulation of HP1a at transcription start sites with stalled polII, the signatures of histone code and polII level/position around the transcriptional start sites that predict both the mRNA level and functionality of genes, and the enrichment of elongating polII within exons at splicing junctions. These features, likely conserved among diverse epigenomes, reveal general strategies for chromatin modifications.

Using Airborne High Spectral Resolution Lidar Data to Evaluate Combined Active Plus Passive Retrievals of Aerosol Extinction Profiles

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Burton, S. P.; Ferrare, R. A.; Hostetler, C. A.; Hair, J. W.; Kittaka, C.; Vaughn, M. A.; Remer, L. A.

2010-01-01

We derive aerosol extinction profiles from airborne and space-based lidar backscatter signals by constraining the retrieval with column aerosol optical thickness (AOT), with no need to rely on assumptions about aerosol type or lidar ratio. The backscatter data were acquired by the NASA Langley Research Center airborne High Spectral Resolution Lidar (HSRL) and by the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) instrument on the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellite. The HSRL also simultaneously measures aerosol extinction coefficients independently using the high spectral resolution lidar technique, thereby providing an ideal data set for evaluating the retrieval. We retrieve aerosol extinction profiles from both HSRL and CALIOP attenuated backscatter data constrained with HSRL, Moderate-Resolution Imaging Spectroradiometer (MODIS), and Multiangle Imaging Spectroradiometer column AOT. The resulting profiles are compared with the aerosol extinction measured by HSRL. Retrievals are limited to cases where the column aerosol thickness is greater than 0.2 over land and 0.15 over water. In the case of large AOT, the results using the Aqua MODIS constraint over water are poorer than Aqua MODIS over land or Terra MODIS. The poorer results relate to an apparent bias in Aqua MODIS AOT over water observed in August 2007. This apparent bias is still under investigation. Finally, aerosol extinction coefficients are derived from CALIPSO backscatter data using AOT from Aqua MODIS for 28 profiles over land and 9 over water. They agree with coincident measurements by the airborne HSRL to within +/-0.016/km +/- 20% for at least two-thirds of land points and within +/-0.028/km +/- 20% for at least two-thirds of ocean points.

Using elastic peak electron spectroscopy for enhanced depth resolution in sputter profiling

International Nuclear Information System (INIS)

Hofmann, S.; Kesler, V.

2002-01-01

Elastic peak electron spectroscopy (EPES) is an alternative to AES in sputter depth profiling of thin film structures. In contrast to AES, EPES depth profiling is not influenced by chemical effects. The high count rate ensures a good signal to noise ratio, that is lower measurement times and/or higher precision. In addition, because of the elastically scattered electrons travel twice through the sample, the effective escape depth is reduced, an important factor for the depth resolution function. Thus, the depth resolution is increased. EPES depth profiling was successfully applied to a Ge/Si multilayer structure. For an elastic peak energy of 1.0 keV the information depth is considerably lower (0.8 nm) as compared to the Ge (LMM, 1147 eV) peak (1.6 nm) used in AES depth profiling, resulting in a respectively improved depth resolution for EPES profiling under otherwise similar profiling conditions. EPES depth profiling is successfully applied to measure small diffusion lengths at Ge/Si interfaces of the order of 1 nm. (Authors)

A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni.

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Anna V Protasio

2012-01-01

Full Text Available Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org and SchistoDB (www.schistodb.net databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research.

Genome-wide DNA Methylation Profiling of Cell-Free Serum DNA in Esophageal Adenocarcinoma and Barrett Esophagus

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Rihong Zhai

2012-01-01

Full Text Available Aberrant DNA methylation (DNAm is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on tumor tissue DNA samples. However, the invasive procedure limits the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNAm (cfDNAm profiles reflect DNAm status in corresponding tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA and Barrett esophagus (BE, EA precursor. We performed genome-wide DNAm profiling in EA tissue DNA (n = 8 and matched serum DNA (n = 8, in serum DNA of BE (n = 10, and in healthy controls (n = 10 using the Infinium HumanMethylation27 BeadChip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNA (r = 0.92 in patients with EA. We selected the most differentially methylated loci to perform hierarchical clustering analysis. We found that 911 loci can discriminate perfectly between EA and control samples, 554 loci can separate EA from BE samples, and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the noninvasive screening of EA and EA premalignant lesions.

Expedient data mining for nontargeted high-resolution LC-MS profiles of biological samples.

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Hnatyshyn, Serhiy; Shipkova, Petia; Sanders, Mark

2013-05-01

The application of high-resolution LC-MS metabolomics for drug candidate toxicity screening reflects phenotypic changes of an organism caused by induced chemical interferences. Its success depends not only on the ability to translate the acquired analytical information into biological knowledge, but also on the timely delivery of the results to aid the decision making process in drug discovery and development. Recent improvements in analytical instrumentation have resulted in the ability to acquire extremely information-rich datasets. These new data collection abilities have shifted the bottleneck in the timeline of metabolomic studies to the data analysis step. This paper describes our approach to expedient data analysis of nontargeted high-resolution LC-MS profiles of biological samples. The workflow is illustrated with the example of metabolomics study of time-dependent fasting in male rats. The results from measurement of 220 endogenous metabolites in urine samples illustrate significant biochemical changes induced by fasting. The developed software enables the reporting of relative quantities of annotated components while maintaining practical turnaround times. Each component annotation in the report is validated using both calculated isotopic peaks patterns and experimentally determined retention time data on standards.

Global assessment of genomic variation in cattle by genome resequencing and high-throughput genotyping

DEFF Research Database (Denmark)

Zhan, Bujie; Fadista, João; Thomsen, Bo

2011-01-01

Background Integration of genomic variation with phenotypic information is an effective approach for uncovering genotype-phenotype associations. This requires an accurate identification of the different types of variation in individual genomes. Results We report the integration of the whole genome...... of split-read and read-pair approaches proved to be complementary in finding different signatures. CNVs were identified on the basis of the depth of sequenced reads, and by using SNP and CGH arrays. Conclusions Our results provide high resolution mapping of diverse classes of genomic variation...

Analysis of genomic imbalances and gene expression changes in transformed follicular lymphoma (FL)

DEFF Research Database (Denmark)

Obel, G.; Farinha, P.; Lam, W.

2005-01-01

American patients with transformed FL. Methods: High-resolution BAC-array comparative genomic hybridisation (CGH) was used to detect genomic imbalances. Gene expression profiling was performed using cDNA microarrays (Affymetrix). Results: Of 9 biopsy pairs identified so far, analysis results of the first 4...

A new method for high-resolution characterization of hydraulic conductivity

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Liu, Gaisheng; Butler, J.J.; Bohling, Geoffrey C.; Reboulet, Ed; Knobbe, Steve; Hyndman, D.W.

2009-01-01

A new probe has been developed for high-resolution characterization of hydraulic conductivity (K) in shallow unconsolidated formations. The probe was recently applied at the Macrodispersion Experiment (MADE) site in Mississippi where K was rapidly characterized at a resolution as fine as 0.015 m, which has not previously been possible. Eleven profiles were obtained with K varying up to 7 orders of magnitude in individual profiles. Currently, high-resolution (0.015-m) profiling has an upper K limit of 10 m/d; lower-resolution (???0.4-m) mode is used in more permeable zones pending modifications. The probe presents a new means to help address unresolved issues of solute transport in heterogeneous systems. Copyright 2009 by the American Geophysical Union.

Genomic profiling of oral squamous cell carcinoma by array-based comparative genomic hybridization.

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Shunichi Yoshioka

Full Text Available We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC and their lymph node metastases, and to identify genomic copy number aberrations (CNAs related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs with their paired lymph node metastases (LNMs, and also those of LNMs with non-metastatic primary tumors (NMPTs. Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.

High Temporal Resolution Tropospheric Wind Profile Observations at NASA Kennedy Space Center During Hurricane Irma

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Decker, Ryan K.; Barbre, Robert E., Jr.; Huddleston, Lisa; Brauer, Thomas; Wilfong, Timothy

2018-01-01

The NASA Kennedy Space Center (KSC) operates a 48-MHz Tropospheric/Stratospheric Doppler Radar Wind Profiler (TDRWP) on a continual basis generating wind profiles between 2-19 km in the support of space launch vehicle operations. A benefit of the continual operability of the system is the ability to provide unique observations of severe weather events such as hurricanes. Over the past two Atlantic Hurricane seasons the TDRWP has made high temporal resolution wind profile observations of Hurricane Irma in 2017 and Hurricane Matthew in 2016. Hurricane Irma was responsible for power outages to approximately 2/3 of Florida's population during its movement over the state(Stein,2017). An overview of the TDRWP system configuration, brief summary of Hurricanes Irma and Matthew storm track in proximity to KSC, characteristics of the tropospheric wind observations from the TDRWP during both events, and discussion of the dissemination of TDRWP data during the event will be presented.

Glacio-tectonic thrust and deformation structures in the Vejle Fjord, Denmark revealed by high-resolution subbottom-profile data

DEFF Research Database (Denmark)

Andresen, Katrine Juul; Boldreel, Lars Ole; Wahlgreen, Katrine Bak

Surface geomorphological features and partial cliff exposures up till now represent the predominant source of information of glaciation related deformation in Denmark. In this study we apply high-resolution marine reflection seismic data from the Vejle Fjord area, supported by gravity and Rumohr...... coring, to document intense glacio-tectonic deformation in the shallow subsurface of Denmark. The subbottom profiler seismic data have a peak frequency around 13 kHz and a vertical resolution in the order of 10-20 cm. The data reveal several variations of glacio-tectonic deformation structures, primarily...... movements from outcrops and shallow cores. The subbottom profiler data provides larger (longer and deeper) sectional views on for instance deformation and deposition complexes related to ice progressions and retreats and thus represents a very good supplement and valuable input to field mapping and outcrops...

Development of cleaved amplified polymorphic sequence (CAPS) and high-resolution melting (HRM) markers from the chloroplast genome of Glycyrrhiza species.

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Jo, Ick-Hyun; Sung, Jwakyung; Hong, Chi-Eun; Raveendar, Sebastin; Bang, Kyong-Hwan; Chung, Jong-Wook

2018-05-01

Licorice ( Glycyrrhiza glabra ) is an important medicinal crop often used as health foods or medicine worldwide. The molecular genetics of licorice is under scarce owing to lack of molecular markers. Here, we have developed cleaved amplified polymorphic sequence (CAPS) and high-resolution melting (HRM) markers based on single nucleotide polymorphisms (SNP) by comparing the chloroplast genomes of two Glycyrrhiza species ( G. glabra and G. lepidota ). The CAPS and HRM markers were tested for diversity analysis with 24 Glycyrrhiza accessions. The restriction profiles generated with CAPS markers classified the accessions (2-4 genotypes) and melting curves (2-3) were obtained from the HRM markers. The number of alleles and major allele frequency were 2-6 and 0.31-0.92, respectively. The genetic distance and polymorphism information content values were 0.16-0.76 and 0.15-0.72, respectively. The phylogenetic relationships among the 24 accessions were estimated using a dendrogram, which classified them into four clades. Except clade III, the remaining three clades included the same species, confirming interspecies genetic correlation. These 18 CAPS and HRM markers might be helpful for genetic diversity assessment and rapid identification of licorice species.

High resolution optical DNA mapping

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Baday, Murat

Many types of diseases including cancer and autism are associated with copy-number variations in the genome. Most of these variations could not be identified with existing sequencing and optical DNA mapping methods. We have developed Multi-color Super-resolution technique, with potential for high throughput and low cost, which can allow us to recognize more of these variations. Our technique has made 10--fold improvement in the resolution of optical DNA mapping. Using a 180 kb BAC clone as a model system, we resolved dense patterns from 108 fluorescent labels of two different colors representing two different sequence-motifs. Overall, a detailed DNA map with 100 bp resolution was achieved, which has the potential to reveal detailed information about genetic variance and to facilitate medical diagnosis of genetic disease.

High Resolution Melt (HRM) analysis is an efficient tool to genotype EMS mutants in complex crop genomes.

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Lochlainn, Seosamh Ó; Amoah, Stephen; Graham, Neil S; Alamer, Khalid; Rios, Juan J; Kurup, Smita; Stoute, Andrew; Hammond, John P; Østergaard, Lars; King, Graham J; White, Phillip J; Broadley, Martin R

2011-12-08

Targeted Induced Loci Lesions IN Genomes (TILLING) is increasingly being used to generate and identify mutations in target genes of crop genomes. TILLING populations of several thousand lines have been generated in a number of crop species including Brassica rapa. Genetic analysis of mutants identified by TILLING requires an efficient, high-throughput and cost effective genotyping method to track the mutations through numerous generations. High resolution melt (HRM) analysis has been used in a number of systems to identify single nucleotide polymorphisms (SNPs) and insertion/deletions (IN/DELs) enabling the genotyping of different types of samples. HRM is ideally suited to high-throughput genotyping of multiple TILLING mutants in complex crop genomes. To date it has been used to identify mutants and genotype single mutations. The aim of this study was to determine if HRM can facilitate downstream analysis of multiple mutant lines identified by TILLING in order to characterise allelic series of EMS induced mutations in target genes across a number of generations in complex crop genomes. We demonstrate that HRM can be used to genotype allelic series of mutations in two genes, BraA.CAX1a and BraA.MET1.a in Brassica rapa. We analysed 12 mutations in BraA.CAX1.a and five in BraA.MET1.a over two generations including a back-cross to the wild-type. Using a commercially available HRM kit and the Lightscanner™ system we were able to detect mutations in heterozygous and homozygous states for both genes. Using HRM genotyping on TILLING derived mutants, it is possible to generate an allelic series of mutations within multiple target genes rapidly. Lines suitable for phenotypic analysis can be isolated approximately 8-9 months (3 generations) from receiving M3 seed of Brassica rapa from the RevGenUK TILLING service.

High Resolution Melt (HRM analysis is an efficient tool to genotype EMS mutants in complex crop genomes

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Lochlainn Seosamh Ó

2011-12-01

Full Text Available Abstract Background Targeted Induced Loci Lesions IN Genomes (TILLING is increasingly being used to generate and identify mutations in target genes of crop genomes. TILLING populations of several thousand lines have been generated in a number of crop species including Brassica rapa. Genetic analysis of mutants identified by TILLING requires an efficient, high-throughput and cost effective genotyping method to track the mutations through numerous generations. High resolution melt (HRM analysis has been used in a number of systems to identify single nucleotide polymorphisms (SNPs and insertion/deletions (IN/DELs enabling the genotyping of different types of samples. HRM is ideally suited to high-throughput genotyping of multiple TILLING mutants in complex crop genomes. To date it has been used to identify mutants and genotype single mutations. The aim of this study was to determine if HRM can facilitate downstream analysis of multiple mutant lines identified by TILLING in order to characterise allelic series of EMS induced mutations in target genes across a number of generations in complex crop genomes. Results We demonstrate that HRM can be used to genotype allelic series of mutations in two genes, BraA.CAX1a and BraA.MET1.a in Brassica rapa. We analysed 12 mutations in BraA.CAX1.a and five in BraA.MET1.a over two generations including a back-cross to the wild-type. Using a commercially available HRM kit and the Lightscanner™ system we were able to detect mutations in heterozygous and homozygous states for both genes. Conclusions Using HRM genotyping on TILLING derived mutants, it is possible to generate an allelic series of mutations within multiple target genes rapidly. Lines suitable for phenotypic analysis can be isolated approximately 8-9 months (3 generations from receiving M3 seed of Brassica rapa from the RevGenUK TILLING service.

UFO: a web server for ultra-fast functional profiling of whole genome protein sequences.

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Meinicke, Peter

2009-09-02

Functional profiling is a key technique to characterize and compare the functional potential of entire genomes. The estimation of profiles according to an assignment of sequences to functional categories is a computationally expensive task because it requires the comparison of all protein sequences from a genome with a usually large database of annotated sequences or sequence families. Based on machine learning techniques for Pfam domain detection, the UFO web server for ultra-fast functional profiling allows researchers to process large protein sequence collections instantaneously. Besides the frequencies of Pfam and GO categories, the user also obtains the sequence specific assignments to Pfam domain families. In addition, a comparison with existing genomes provides dissimilarity scores with respect to 821 reference proteomes. Considering the underlying UFO domain detection, the results on 206 test genomes indicate a high sensitivity of the approach. In comparison with current state-of-the-art HMMs, the runtime measurements show a considerable speed up in the range of four orders of magnitude. For an average size prokaryotic genome, the computation of a functional profile together with its comparison typically requires about 10 seconds of processing time. For the first time the UFO web server makes it possible to get a quick overview on the functional inventory of newly sequenced organisms. The genome scale comparison with a large number of precomputed profiles allows a first guess about functionally related organisms. The service is freely available and does not require user registration or specification of a valid email address.

UFO: a web server for ultra-fast functional profiling of whole genome protein sequences

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Meinicke Peter

2009-09-01

Full Text Available Abstract Background Functional profiling is a key technique to characterize and compare the functional potential of entire genomes. The estimation of profiles according to an assignment of sequences to functional categories is a computationally expensive task because it requires the comparison of all protein sequences from a genome with a usually large database of annotated sequences or sequence families. Description Based on machine learning techniques for Pfam domain detection, the UFO web server for ultra-fast functional profiling allows researchers to process large protein sequence collections instantaneously. Besides the frequencies of Pfam and GO categories, the user also obtains the sequence specific assignments to Pfam domain families. In addition, a comparison with existing genomes provides dissimilarity scores with respect to 821 reference proteomes. Considering the underlying UFO domain detection, the results on 206 test genomes indicate a high sensitivity of the approach. In comparison with current state-of-the-art HMMs, the runtime measurements show a considerable speed up in the range of four orders of magnitude. For an average size prokaryotic genome, the computation of a functional profile together with its comparison typically requires about 10 seconds of processing time. Conclusion For the first time the UFO web server makes it possible to get a quick overview on the functional inventory of newly sequenced organisms. The genome scale comparison with a large number of precomputed profiles allows a first guess about functionally related organisms. The service is freely available and does not require user registration or specification of a valid email address.

High Resolution Typing by Whole Genome Mapping Enables Discrimination of LA-MRSA (CC398) Strains and Identification of Transmission Events

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Bosch, Thijs; Verkade, Erwin; van Luit, Martijn; Pot, Bruno; Vauterin, Paul; Burggrave, Ronald; Savelkoul, Paul; Kluytmans, Jan; Schouls, Leo

2013-01-01

After its emergence in 2003, a livestock-associated (LA-)MRSA clade (CC398) has caused an impressive increase in the number of isolates submitted for the Dutch national MRSA surveillance and now comprises 40% of all isolates. The currently used molecular typing techniques have limited discriminatory power for this MRSA clade, which hampers studies on the origin and transmission routes. Recently, a new molecular analysis technique named whole genome mapping was introduced. This method creates high-resolution, ordered whole genome restriction maps that may have potential for strain typing. In this study, we assessed and validated the capability of whole genome mapping to differentiate LA-MRSA isolates. Multiple validation experiments showed that whole genome mapping produced highly reproducible results. Assessment of the technique on two well-documented MRSA outbreaks showed that whole genome mapping was able to confirm one outbreak, but revealed major differences between the maps of a second, indicating that not all isolates belonged to this outbreak. Whole genome mapping of LA-MRSA isolates that were epidemiologically unlinked provided a much higher discriminatory power than spa-typing or MLVA. In contrast, maps created from LA-MRSA isolates obtained during a proven LA-MRSA outbreak were nearly indistinguishable showing that transmission of LA-MRSA can be detected by whole genome mapping. Finally, whole genome maps of LA-MRSA isolates originating from two unrelated veterinarians and their household members showed that veterinarians may carry and transmit different LA-MRSA strains at the same time. No such conclusions could be drawn based spa-typing and MLVA. Although PFGE seems to be suitable for molecular typing of LA-MRSA, WGM provides a much higher discriminatory power. Furthermore, whole genome mapping can provide a comparison with other maps within 2 days after the bacterial culture is received, making it suitable to investigate transmission events and

Quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy for identification of antidiabetic constituents in crude root bark of Morus alba L.

Science.gov (United States)

Zhao, Yong; Kongstad, Kenneth Thermann; Jäger, Anna Katharina; Nielsen, John; Staerk, Dan

2018-06-29

In this paper, quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling combined with HPLC-HRMS-SPE-NMR were used for studying the polypharmacological properties of crude root bark extract of Morus alba L. This species is used as an anti-diabetic principle in many traditional treatment systems around the world, and the crude ethyl acetate extract of M. alba root bark was found to inhibit α-glucosidase, α-amylase and protein-tyrosine phosphatase 1B (PTP1B) with IC 50 values of 1.70 ± 0.72, 5.16 ± 0.69, and 5.07 ± 0.68 μg/mL as well as showing radical scavenging activity equaling a TEAC value of (3.82 ± 0.14) × 10 4  mM per gram extract. Subsequent investigation of the crude extract using quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling provided a quadruple biochromatogram that allowed direct correlation of the HPLC peaks with one or more of the tested bioactivities. This was used to target subsequent HPLC-HRMS-SPE-NMR analysis towards peaks representing bioactive analytes, and led to identification of a new Diels-Alder adduct named Moracenin E as well as a series of Diels-Alder adducts and isoprenylated flavonoids as potent α-glucosidase and α-amylase inhibitors with IC 50 values in the range of 0.60-27.15 μM and 1.22-69.38 μM, respectively. In addition, these compounds and two 2-arylbenzofurans were found to be potent PTP1B inhibitors with IC 50 values ranging from 4.04 to 21.67 μM. The high-resolution radical scavenging profile also revealed that almost all of the compounds possess radical scavenging activity. In conclusion the quadruple high-resolution profiling method presented here allowed a detailed profiling of individual constituents in crude root bark extract of M. alba, and the method provides a general tool for detailed mapping of bioactive constituents in polypharmacological herbal remedies. Copyright © 2018 Elsevier B.V. All rights reserved.

High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli.

Science.gov (United States)

van Koningsbruggen, Silvana; Gierlinski, Marek; Schofield, Pietá; Martin, David; Barton, Geoffey J; Ariyurek, Yavuz; den Dunnen, Johan T; Lamond, Angus I

2010-11-01

The nuclear space is mostly occupied by chromosome territories and nuclear bodies. Although this organization of chromosomes affects gene function, relatively little is known about the role of nuclear bodies in the organization of chromosomal regions. The nucleolus is the best-studied subnuclear structure and forms around the rRNA repeat gene clusters on the acrocentric chromosomes. In addition to rDNA, other chromatin sequences also surround the nucleolar surface and may even loop into the nucleolus. These additional nucleolar-associated domains (NADs) have not been well characterized. We present here a whole-genome, high-resolution analysis of chromatin endogenously associated with nucleoli. We have used a combination of three complementary approaches, namely fluorescence comparative genome hybridization, high-throughput deep DNA sequencing and photoactivation combined with time-lapse fluorescence microscopy. The data show that specific sequences from most human chromosomes, in addition to the rDNA repeat units, associate with nucleoli in a reproducible and heritable manner. NADs have in common a high density of AT-rich sequence elements, low gene density and a statistically significant enrichment in transcriptionally repressed genes. Unexpectedly, both the direct DNA sequencing and fluorescence photoactivation data show that certain chromatin loci can specifically associate with either the nucleolus, or the nuclear envelope.

High-resolution comparative mapping among man, cattle and mouse suggests a role for repeat sequences in mammalian genome evolution

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Rodolphe François

2006-08-01

Full Text Available Abstract Background Comparative mapping provides new insights into the evolutionary history of genomes. In particular, recent studies in mammals have suggested a role for segmental duplication in genome evolution. In some species such as Drosophila or maize, transposable elements (TEs have been shown to be involved in chromosomal rearrangements. In this work, we have explored the presence of interspersed repeats in regions of chromosomal rearrangements, using an updated high-resolution integrated comparative map among cattle, man and mouse. Results The bovine, human and mouse comparative autosomal map has been constructed using data from bovine genetic and physical maps and from FISH-mapping studies. We confirm most previous results but also reveal some discrepancies. A total of 211 conserved segments have been identified between cattle and man, of which 33 are new segments and 72 correspond to extended, previously known segments. The resulting map covers 91% and 90% of the human and bovine genomes, respectively. Analysis of breakpoint regions revealed a high density of species-specific interspersed repeats in the human and mouse genomes. Conclusion Analysis of the breakpoint regions has revealed specific repeat density patterns, suggesting that TEs may have played a significant role in chromosome evolution and genome plasticity. However, we cannot rule out that repeats and breakpoints accumulate independently in the few same regions where modifications are better tolerated. Likewise, we cannot ascertain whether increased TE density is the cause or the consequence of chromosome rearrangements. Nevertheless, the identification of high density repeat clusters combined with a well-documented repeat phylogeny should highlight probable breakpoints, and permit their precise dating. Combining new statistical models taking the present information into account should help reconstruct ancestral karyotypes.

Effects of high hydrostatic pressure on genomic expression profiling of porcine parthenogenetic activated and cloned embryos

DEFF Research Database (Denmark)

Lin, Lin; Luo, Yonglun; Sørensen, Peter

2014-01-01

derived by PA or HMC. Hierarchical clustering depicted stage-specific genomic expression profiling. At the 4-cell and blastocyst stages, 103 and 163 transcripts were differentially expressed between the HMC and PA embryos, respectively (P

Rapid high resolution genotyping of Francisella tularensis by whole genome sequence comparison of annotated genes ("MLST+".

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Markus H Antwerpen

Full Text Available The zoonotic disease tularemia is caused by the bacterium Francisella tularensis. This pathogen is considered as a category A select agent with potential to be misused in bioterrorism. Molecular typing based on DNA-sequence like canSNP-typing or MLVA has become the accepted standard for this organism. Due to the organism's highly clonal nature, the current typing methods have reached their limit of discrimination for classifying closely related subpopulations within the subspecies F. tularensis ssp. holarctica. We introduce a new gene-by-gene approach, MLST+, based on whole genome data of 15 sequenced F. tularensis ssp. holarctica strains and apply this approach to investigate an epidemic of lethal tularemia among non-human primates in two animal facilities in Germany. Due to the high resolution of MLST+ we are able to demonstrate that three independent clones of this highly infectious pathogen were responsible for these spatially and temporally restricted outbreaks.

An object model for genome information at all levels of resolution

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Honda, S.; Parrott, N.W.; Smith, R.; Lawrence, C.

1993-12-31

An object model for genome data at all levels of resolution is described. The model was derived by considering the requirements for representing genome related objects in three application domains: genome maps, large-scale DNA sequencing, and exploring functional information in gene and protein sequences. The methodology used for the object-oriented analysis is also described.

A high-density Diversity Arrays Technology (DArT microarray for genome-wide genotyping in Eucalyptus

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Myburg Alexander A

2010-06-01

Full Text Available Abstract Background A number of molecular marker technologies have allowed important advances in the understanding of the genetics and evolution of Eucalyptus, a genus that includes over 700 species, some of which are used worldwide in plantation forestry. Nevertheless, the average marker density achieved with current technologies remains at the level of a few hundred markers per population. Furthermore, the transferability of markers produced with most existing technology across species and pedigrees is usually very limited. High throughput, combined with wide genome coverage and high transferability are necessary to increase the resolution, speed and utility of molecular marker technology in eucalypts. We report the development of a high-density DArT genome profiling resource and demonstrate its potential for genome-wide diversity analysis and linkage mapping in several species of Eucalyptus. Findings After testing several genome complexity reduction methods we identified the PstI/TaqI method as the most effective for Eucalyptus and developed 18 genomic libraries from PstI/TaqI representations of 64 different Eucalyptus species. A total of 23,808 cloned DNA fragments were screened and 13,300 (56% were found to be polymorphic among 284 individuals. After a redundancy analysis, 6,528 markers were selected for the operational array and these were supplemented with 1,152 additional clones taken from a library made from the E. grandis tree whose genome has been sequenced. Performance validation for diversity studies revealed 4,752 polymorphic markers among 174 individuals. Additionally, 5,013 markers showed segregation when screened using six inter-specific mapping pedigrees, with an average of 2,211 polymorphic markers per pedigree and a minimum of 859 polymorphic markers that were shared between any two pedigrees. Conclusions This operational DArT array will deliver 1,000-2,000 polymorphic markers for linkage mapping in most eucalypt pedigrees

High-resolution genetic map for understanding the effect of genome-wide recombination rate on nucleotide diversity in watermelon.

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Reddy, Umesh K; Nimmakayala, Padma; Levi, Amnon; Abburi, Venkata Lakshmi; Saminathan, Thangasamy; Tomason, Yan R; Vajja, Gopinath; Reddy, Rishi; Abburi, Lavanya; Wehner, Todd C; Ronin, Yefim; Karol, Abraham

2014-09-15

We used genotyping by sequencing to identify a set of 10,480 single nucleotide polymorphism (SNP) markers for constructing a high-resolution genetic map of 1096 cM for watermelon. We assessed the genome-wide variation in recombination rate (GWRR) across the map and found an association between GWRR and genome-wide nucleotide diversity. Collinearity between the map and the genome-wide reference sequence for watermelon was studied to identify inconsistency and chromosome rearrangements. We assessed genome-wide nucleotide diversity, linkage disequilibrium (LD), and selective sweep for wild, semi-wild, and domesticated accessions of Citrullus lanatus var. lanatus to track signals of domestication. Principal component analysis combined with chromosome-wide phylogenetic study based on 1563 SNPs obtained after LD pruning with minor allele frequency of 0.05 resolved the differences between semi-wild and wild accessions as well as relationships among worldwide sweet watermelon. Population structure analysis revealed predominant ancestries for wild, semi-wild, and domesticated watermelons as well as admixture of various ancestries that were important for domestication. Sliding window analysis of Tajima's D across various chromosomes was used to resolve selective sweep. LD decay was estimated for various chromosomes. We identified a strong selective sweep on chromosome 3 consisting of important genes that might have had a role in sweet watermelon domestication. Copyright © 2014 Reddy et al.

Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia

DEFF Research Database (Denmark)

Gunnarsson, Rebeqa; Mansouri, Larry; Isaksson, Anders

2011-01-01

High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic...... profiles from sequential patients' samples allows detection of clonal evolution....

High-resolution moisture profiles from full-waveform probabilistic inversion of TDR signals

Science.gov (United States)

Laloy, Eric; Huisman, Johan Alexander; Jacques, Diederik

2014-11-01

This study presents an novel Bayesian inversion scheme for high-dimensional undetermined TDR waveform inversion. The methodology quantifies uncertainty in the moisture content distribution, using a Gaussian Markov random field (GMRF) prior as regularization operator. A spatial resolution of 1 cm along a 70-cm long TDR probe is considered for the inferred moisture content. Numerical testing shows that the proposed inversion approach works very well in case of a perfect model and Gaussian measurement errors. Real-world application results are generally satisfying. For a series of TDR measurements made during imbibition and evaporation from a laboratory soil column, the average root-mean-square error (RMSE) between maximum a posteriori (MAP) moisture distribution and reference TDR measurements is 0.04 cm3 cm-3. This RMSE value reduces to less than 0.02 cm3 cm-3 for a field application in a podzol soil. The observed model-data discrepancies are primarily due to model inadequacy, such as our simplified modeling of the bulk soil electrical conductivity profile. Among the important issues that should be addressed in future work are the explicit inference of the soil electrical conductivity profile along with the other sampled variables, the modeling of the temperature-dependence of the coaxial cable properties and the definition of an appropriate statistical model of the residual errors.

Non-Cooperative Target Recognition by Means of Singular Value Decomposition Applied to Radar High Resolution Range Profiles

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Patricia López-Rodríguez

2014-12-01

Full Text Available Radar high resolution range profiles are widely used among the target recognition community for the detection and identification of flying targets. In this paper, singular value decomposition is applied to extract the relevant information and to model each aircraft as a subspace. The identification algorithm is based on angle between subspaces and takes place in a transformed domain. In order to have a wide database of radar signatures and evaluate the performance, simulated range profiles are used as the recognition database while the test samples comprise data of actual range profiles collected in a measurement campaign. Thanks to the modeling of aircraft as subspaces only the valuable information of each target is used in the recognition process. Thus, one of the main advantages of using singular value decomposition, is that it helps to overcome the notable dissimilarities found in the shape and signal-to-noise ratio between actual and simulated profiles due to their difference in nature. Despite these differences, the recognition rates obtained with the algorithm are quite promising.

Radiation hybrid mapping as one of the main methods of the creation of high resolution maps of human and animal genomes

International Nuclear Information System (INIS)

Sulimova, G.E.; Kompanijtsev, A.A.; Mojsyak, E.V.; Rakhmanaliev, Eh.R.; Klimov, E.A.; Udina, I.G.; Zakharov, I.A.

2000-01-01

Radiation hybrid mapping (RH mapping) is considered as one of the main method of constructing physical maps of mammalian genomes. In introduction, theoretical prerequisites of developing of the RH mapping and statistical methods of data analysis are discussed. Comparative characteristics of universal commercial panels of the radiation hybrid somatic cells (RH panels) are shown. In experimental part of the work, RH mapping is used to localize nucleotide sequences adjacent to Not I sites of human chromosome 3 with the aim to integrate contig map of Nor I clones to comprehensive maps of human genome. Five nucleotide sequences adjacent to the sites of integration of papilloma virus in human genome and expressed in the cells of cervical cancer involved localized. It is demonstrated that the region 13q14.3-q21.1 was enriched with nucleotide sequences involved in the processes of carcinogenesis. RH mapping can be considered as one of the most perspective applications of modern radiation biology in the field of molecular genetics, that is, in constructing physical maps of mammalian genomes with high resolution level [ru

A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

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Graciana Diez-Roux

Full Text Available Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org, consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

Cerebrospinal fluid metabolic profiles in multiple sclerosis and degenerative dementias obtained by high resolution proton magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Vion-Dury, J.; Confort-Gouny, S.; Maillet, S.; Cozzone, P.J.; Nicoli, F.; Gastaut, J.L.

1996-01-01

We have analyzed the cerebrospinal fluid (CSF) of 19 patients with multiple sclerosis (MS), 12 patients with degenerative dementia and 17 control patients using in vitro high resolution proton magnetic resonance spectroscopy (MRS) at 400 MHz. The CSF metabolic profile is slightly modified in MS patients (increased lactate and fructose concentrations, decreased creatinine and phenylalanine concentrations) and is not correlated with the intensity of the intrathecal inflammation. Proton MRS of CSF does not differentiate relapsing-remitting MS and primary progressive MS. We have not detected any specific abnormal resonance in native or lyophilized CSF. The CSF metabolic profile of demented patients is much more altered (increased concentration of lactate, pyruvate, alanine, lysine, valine, leucine-isoleucine, tyrosine, glutamine) and is in agreement with a brain oxidative metabolism impairment as already described in Alzheimer's disease. Unassigned abnormal but non specific or constant resonances have been detected on MR spectra of demented patients. CSF inositol concentration is also increased in the CSF of patients with Alzheimer's disease. In vitro high resolution proton MRS of the CSF constitutes a new and original way to explore CSF for the differential and/or early diagnosis of dementias, as a complement to in vivo proton cerebral MRS. (authors). 22 refs., 4 figs., 2 tabs

Cerebrospinal fluid metabolic profiles in multiple sclerosis and degenerative dementias obtained by high resolution proton magnetic resonance spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Vion-Dury, J.; Confort-Gouny, S.; Maillet, S.; Cozzone, P.J. [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France); Nicoli, F. [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France)]|[Hopital Sainte-Marguerite, 13 - Marseille (France); Gastaut, J.L. [Hopital Sainte-Marguerite, 13 - Marseille (France)

1996-07-01

We have analyzed the cerebrospinal fluid (CSF) of 19 patients with multiple sclerosis (MS), 12 patients with degenerative dementia and 17 control patients using in vitro high resolution proton magnetic resonance spectroscopy (MRS) at 400 MHz. The CSF metabolic profile is slightly modified in MS patients (increased lactate and fructose concentrations, decreased creatinine and phenylalanine concentrations) and is not correlated with the intensity of the intrathecal inflammation. Proton MRS of CSF does not differentiate relapsing-remitting MS and primary progressive MS. We have not detected any specific abnormal resonance in native or lyophilized CSF. The CSF metabolic profile of demented patients is much more altered (increased concentration of lactate, pyruvate, alanine, lysine, valine, leucine-isoleucine, tyrosine, glutamine) and is in agreement with a brain oxidative metabolism impairment as already described in Alzheimer`s disease. Unassigned abnormal but non specific or constant resonances have been detected on MR spectra of demented patients. CSF inositol concentration is also increased in the CSF of patients with Alzheimer`s disease. In vitro high resolution proton MRS of the CSF constitutes a new and original way to explore CSF for the differential and/or early diagnosis of dementias, as a complement to in vivo proton cerebral MRS. (authors). 22 refs., 4 figs., 2 tabs.

High-resolution genomic fingerprinting of Campylobacter jejuni and Campylobacter coli by analysis of amplified fragment length polymorphisms

DEFF Research Database (Denmark)

Kokotovic, Branko; On, Stephen L.W.

1999-01-01

A method for high-resolution genomic fingerprinting of the enteric pathogens Campylobacter jejuni and Campylobacter coli, based on the determination of amplified fragment length polymorphism, is described. The potential of this method for molecular epidemiological studies of these species...... is evaluated with 50 type, reference, and well-characterised field strains. Amplified fragment length polymorphism fingerprints comprised over 60 bands detected in the size range 35-500 bp. Groups of outbreak strains, replicate subcultures, and 'genetically identical' strains from humans, poultry and cattle......, proved indistinguishable by amplified fragment length polymorphism fingerprinting, but were differentiated fi-om unrelated isolates. Previously unknown relationships between three hippurate-negative C. jejuni strains, and two C. coil var, hyoilei strains, were identified. These relationships corresponded...

Microarray-based ultra-high resolution discovery of genomic deletion mutations

Science.gov (United States)

2014-01-01

Background Oligonucleotide microarray-based comparative genomic hybridization (CGH) offers an attractive possible route for the rapid and cost-effective genome-wide discovery of deletion mutations. CGH typically involves comparison of the hybridization intensities of genomic DNA samples with microarray chip representations of entire genomes, and has widespread potential application in experimental research and medical diagnostics. However, the power to detect small deletions is low. Results Here we use a graduated series of Arabidopsis thaliana genomic deletion mutations (of sizes ranging from 4 bp to ~5 kb) to optimize CGH-based genomic deletion detection. We show that the power to detect smaller deletions (4, 28 and 104 bp) depends upon oligonucleotide density (essentially the number of genome-representative oligonucleotides on the microarray chip), and determine the oligonucleotide spacings necessary to guarantee detection of deletions of specified size. Conclusions Our findings will enhance a wide range of research and clinical applications, and in particular will aid in the discovery of genomic deletions in the absence of a priori knowledge of their existence. PMID:24655320

Genome-wide deficiency screen for the genomic regions responsible for heat resistance in Drosophila melanogaster

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Teramura Kouhei

2011-06-01

Full Text Available Abstract Background Temperature adaptation is one of the most important determinants of distribution and population size of organisms in nature. Recently, quantitative trait loci (QTL mapping and gene expression profiling approaches have been used for detecting candidate genes for heat resistance. However, the resolution of QTL mapping is not high enough to examine the individual effects of various genes in each QTL. Heat stress-responsive genes, characterized by gene expression profiling studies, are not necessarily responsible for heat resistance. Some of these genes may be regulated in association with the heat stress response of other genes. Results To evaluate which heat-responsive genes are potential candidates for heat resistance with higher resolution than previous QTL mapping studies, we performed genome-wide deficiency screen for QTL for heat resistance. We screened 439 isogenic deficiency strains from the DrosDel project, covering 65.6% of the Drosophila melanogaster genome in order to map QTL for thermal resistance. As a result, we found 19 QTL for heat resistance, including 3 novel QTL outside the QTL found in previous studies. Conclusion The QTL found in this study encompassed 19 heat-responsive genes found in the previous gene expression profiling studies, suggesting that they were strong candidates for heat resistance. This result provides new insights into the genetic architecture of heat resistance. It also emphasizes the advantages of genome-wide deficiency screen using isogenic deficiency libraries.

Massively parallel digital high resolution melt for rapid and absolutely quantitative sequence profiling

Science.gov (United States)

Velez, Daniel Ortiz; Mack, Hannah; Jupe, Julietta; Hawker, Sinead; Kulkarni, Ninad; Hedayatnia, Behnam; Zhang, Yang; Lawrence, Shelley; Fraley, Stephanie I.

2017-02-01

In clinical diagnostics and pathogen detection, profiling of complex samples for low-level genotypes represents a significant challenge. Advances in speed, sensitivity, and extent of multiplexing of molecular pathogen detection assays are needed to improve patient care. We report the development of an integrated platform enabling the identification of bacterial pathogen DNA sequences in complex samples in less than four hours. The system incorporates a microfluidic chip and instrumentation to accomplish universal PCR amplification, High Resolution Melting (HRM), and machine learning within 20,000 picoliter scale reactions, simultaneously. Clinically relevant concentrations of bacterial DNA molecules are separated by digitization across 20,000 reactions and amplified with universal primers targeting the bacterial 16S gene. Amplification is followed by HRM sequence fingerprinting in all reactions, simultaneously. The resulting bacteria-specific melt curves are identified by Support Vector Machine learning, and individual pathogen loads are quantified. The platform reduces reaction volumes by 99.995% and achieves a greater than 200-fold increase in dynamic range of detection compared to traditional PCR HRM approaches. Type I and II error rates are reduced by 99% and 100% respectively, compared to intercalating dye-based digital PCR (dPCR) methods. This technology could impact a number of quantitative profiling applications, especially infectious disease diagnostics.

High-Resolution Profiling of Drosophila Replication Start Sites Reveals a DNA Shape and Chromatin Signature of Metazoan Origins

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Federico Comoglio

2015-05-01

Full Text Available At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, the genetic and chromatin features defining metazoan replication start sites remain largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and suggest that they transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites. DNA shape and chromatin configurations, not strict sequence motifs, mark and predict origins in higher eukaryotes. We further examine the link between transcription and origin firing and reveal that modulation of origin activity across cell types is intimately linked to cell-type-specific transcriptional programs. Our study unravels conserved origin features and provides unique insights into the relationship among DNA topology, chromatin, transcription, and replication initiation across metazoa.

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.

Science.gov (United States)

Gay, Laurie M; Kim, Sungeun; Fedorchak, Kyle; Kundranda, Madappa; Odia, Yazmin; Nangia, Chaitali; Battiste, James; Colon-Otero, Gerardo; Powell, Steven; Russell, Jeffery; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Ali, Siraj M; Stephens, Philip J; Miller, Vincent A; Ross, Jeffrey S

2017-07-01

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X. The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA , NF1 , CDKN2A , and CDKN2C occurring in 7% of samples. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB. Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered

High-resolution bacterial growth inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of antibacterial constituents in Chinese plants used to treat snakebites

DEFF Research Database (Denmark)

Liu, Yueqiu; Nielsen, Mia; Stærk, Dan

2014-01-01

Bacillus subtilis, Staphylococcus aureus, Escherichia coli or Pseudomonas aeruginosa. The biochromatograms demonstrated that tannins play a main role for the bacterial growth inhibition observed for all above-mentioned plants except for Polygonum cuspidatum. Furthermore, the high-resolution bacterial...... growth inhibition profiling combined with HPLC–HRMS–SPE–NMR allowed fast identification of three non-tannin active compounds, i.e., piceid, resveratrol and emodin from ethanol extract of Polygonum cuspidatum. Conclusion The high-resolution bacterial growth inhibition profiling allowed fast pinpointing...... of constituents responsible for the bioactivity, e.g., either showing tannins being the main bacterial growth inhibitors as observed for the majority of the active plants, or combined with HPLC–HRMS–SPE–NMR for fast structural identification of non-tannin constituents correlated with antibacterial activity....

Genomic and Expression Profiling of Benign and Malignant Nerve Sheath Profiling of Benign and Malignant Nerve Sheath

Science.gov (United States)

2007-05-01

Benign and Malignant Nerve Sheath Tumors in Neurofibromatosis Patients PRINCIPAL INVESTIGATOR: Matt van de Rijn, M.D., Ph.D. Torsten...Annual 3. DATES COVERED 1 May 2006 –30 Apr 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Genomic and Expression Profiling of Benign and Malignant Nerve...Award Number: DAMD17-03-1-0297 Title: Genomic and Expression Profiling of Benign and Malignant Nerve Sheath Tumors in Neurofibromatosis

Genome U-Plot: a whole genome visualization.

Science.gov (United States)

Gaitatzes, Athanasios; Johnson, Sarah H; Smadbeck, James B; Vasmatzis, George

2018-05-15

The ability to produce and analyze whole genome sequencing (WGS) data from samples with structural variations (SV) generated the need to visualize such abnormalities in simplified plots. Conventional two-dimensional representations of WGS data frequently use either circular or linear layouts. There are several diverse advantages regarding both these representations, but their major disadvantage is that they do not use the two-dimensional space very efficiently. We propose a layout, termed the Genome U-Plot, which spreads the chromosomes on a two-dimensional surface and essentially quadruples the spatial resolution. We present the Genome U-Plot for producing clear and intuitive graphs that allows researchers to generate novel insights and hypotheses by visualizing SVs such as deletions, amplifications, and chromoanagenesis events. The main features of the Genome U-Plot are its layered layout, its high spatial resolution and its improved aesthetic qualities. We compare conventional visualization schemas with the Genome U-Plot using visualization metrics such as number of line crossings and crossing angle resolution measures. Based on our metrics, we improve the readability of the resulting graph by at least 2-fold, making apparent important features and making it easy to identify important genomic changes. A whole genome visualization tool with high spatial resolution and improved aesthetic qualities. An implementation and documentation of the Genome U-Plot is publicly available at https://github.com/gaitat/GenomeUPlot. vasmatzis.george@mayo.edu. Supplementary data are available at Bioinformatics online.

PanCoreGen - Profiling, detecting, annotating protein-coding genes in microbial genomes.

Science.gov (United States)

Paul, Sandip; Bhardwaj, Archana; Bag, Sumit K; Sokurenko, Evgeni V; Chattopadhyay, Sujay

2015-12-01

A large amount of genomic data, especially from multiple isolates of a single species, has opened new vistas for microbial genomics analysis. Analyzing the pan-genome (i.e. the sum of genetic repertoire) of microbial species is crucial in understanding the dynamics of molecular evolution, where virulence evolution is of major interest. Here we present PanCoreGen - a standalone application for pan- and core-genomic profiling of microbial protein-coding genes. PanCoreGen overcomes key limitations of the existing pan-genomic analysis tools, and develops an integrated annotation-structure for a species-specific pan-genomic profile. It provides important new features for annotating draft genomes/contigs and detecting unidentified genes in annotated genomes. It also generates user-defined group-specific datasets within the pan-genome. Interestingly, analyzing an example-set of Salmonella genomes, we detect potential footprints of adaptive convergence of horizontally transferred genes in two human-restricted pathogenic serovars - Typhi and Paratyphi A. Overall, PanCoreGen represents a state-of-the-art tool for microbial phylogenomics and pathogenomics study. Copyright © 2015 Elsevier Inc. All rights reserved.

Dislocation density and Burgers vector population in fiber-textured Ni thin films determined by high-resolution X-ray line profile analysis

DEFF Research Database (Denmark)

Csiszár, Gábor; Pantleon, Karen; Alimadadi, Hossein

2012-01-01

distribution are determined by high-resolution X-ray diffraction line profile analysis. The substructure parameters are correlated with the strength of the films by using the combined Taylor and Hall-Petch relations. The convolutional multiple whole profile method is used to obtain the substructure parameters......Nanocrystalline Ni thin films have been produced by direct current electrodeposition with different additives and current density in order to obtain 〈100〉, 〈111〉 and 〈211〉 major fiber textures. The dislocation density, the Burgers vector population and the coherently scattering domain size...

Functional profiling of cyanobacterial genomes and its role in ecological adaptations

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Ratna Prabha

2016-09-01

Full Text Available With the availability of complete genome sequences of many cyanobacterial species, it is becoming feasible to study the broad prospective of the environmental adaptation and the overall changes at transcriptional and translational level in these organisms. In the evolutionary phase, niche-specific competitive forces have resulted in specific features of the cyanobacterial genomes. In this study, functional composition of the 84 different cyanobacterial genomes and their adaptations to different environments was examined by identifying the genomic composition for specific cellular processes, which reflect their genomic functional profile and ecological adaptation. It was identified that among cyanobacterial genomes, metabolic genes have major share over other categories and differentiation of genomic functional profile was observed for the species inhabiting different habitats. The cyanobacteria of freshwater and other habitats accumulate large number of poorly characterized genes. Strain specific functions were also reported in many cyanobacterial members, of which an important feature was the occurrence of phage-related sequences. From this study, it can be speculated that habitat is one of the major factors in giving the shape of functional composition of cyanobacterial genomes towards their ecological adaptations.

High-resolution hydrogen profiling in AlGaN/GaN heterostructures grown by different epitaxial methods

Energy Technology Data Exchange (ETDEWEB)

Gonzalez-Posada Flores, F; Redondo-Cubero, A; Bengoechea, A; Brana, A F; Munoz, E [Instituto de Sistemas Optoelectronicos y Microtecnologia (ISOM) and Dpto. IngenierIa Electronica (DIE), ETSI de Telecomunicacion, Universidad Politecnica de Madrid, E-28040 Madrid (Spain); Gago, R [Centro de Micro-Analisis de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Jimenez, A [Dpto. Electronica, Escuela Politecnica Superior, Universidad de Alcala, E-28805 Alcala de Henares, Madrid (Spain); Grambole, D, E-mail: fposada@die.upm.e [Institute of Ion Beam Physics and Materials Research, Forschungszentrum Dresden-Rossendorf, PF 51019, D-01314 Dresden (Germany)

2009-03-07

Hydrogen (H) incorporation into AlGaN/GaN heterostructures used in high electron mobility transistors, grown by different methods, is studied by high-resolution depth profiling. Samples grown on sapphire and Si(1 1 1) substrates by molecular-beam epitaxy and metal-organic vapour phase epitaxy; involving H-free and H-containing precursors, were analysed to evaluate the eventual incorporation of H into the wafer. The amount of H was measured by means of nuclear reaction analysis (NRA) using the {sup 1}H({sup 15}N,{alpha}{gamma}){sup 12}C reaction up to a depth of {approx}110 nm into the heterostructures. Interestingly, the H profiles are similar in all the samples analysed, with an increasing H content towards the surface and a negligible H incorporation into the GaN layer (0.24 {+-} 0.08 at%) or at the AlGaN/GaN interface. Therefore, NRA shows that H uptake is not related to the growth process or technique employed and that H contamination may be due to external sources after growth. The eventual correlation between topographical defects on the AlGaN surface and the H concentration are also discussed.

Application of high resolution SNP arrays in patients with congenital ...

Indian Academy of Sciences (India)

clinical experience in implementing whole-genome high-resolution SNP arrays to investigate 33 patients with syndromic and .... Online Mendelian Inheritance in Man database (OMIM, ..... of damaged mitochondria through either autophagy or mito- ..... malformations: associations with maternal and infant character- istics in a ...

High resolution resistivity measurements at the Down Ampney research site

International Nuclear Information System (INIS)

Hallam, J.R.; Jackson, P.D.; Rainsbury, M.; Raines, M.

1991-01-01

A new high resolution resistivity surveying method is described for fault detection and characterisation. The resolution is shown to be significantly higher than conventional apparent resistivity profiling when applied to geological discontinuities such as faults. Nominal fault locations have been determined to an accuracy of 0.5 m, as proven by drilling. Two dimensional profiling and image enhancement of the resulting 2-D data set indicated the possibility of subsidiary fractures and/or lateral changes within the clay to clay' fault zone. The increased resolution allows greater confidence to be placed on both the fault detection and lateral perturbations derived from processed resistance and resistivity images. (Author)

High-throughput sequencing of core STR loci for forensic genetic investigations using the Roche Genome Sequencer FLX platform

DEFF Research Database (Denmark)

Fordyce, Sarah Louise; Avila Arcos, Maria del Carmen; Rockenbauer, Eszter

2011-01-01

repeat units. These methods do not allow for the full resolution of STR base composition that sequencing approaches could provide. Here we present an STR profiling method based on the use of the Roche Genome Sequencer (GS) FLX to simultaneously sequence multiple core STR loci. Using this method...

High-resolution bioactivity profiling combined with HPLC-HRMS-SPE-NMR: α-glucosidase inhibitors and acetylated ellagic acid rhamnosides from Myrcia palustris DC. (Myrtaceae)

DEFF Research Database (Denmark)

Wubshet, Sileshi Gizachew; Moresco, Henrique H.; Tahtah, Yousof

2015-01-01

, and therefore improved drug leads or functional foods containing α-glucosidase inhibitors are needed for management of blood glucose. In this study, leaves of Myrcia palustris were investigated by high-resolution α-glucosidase inhibition profiling combined with HPLC–HRMS–SPE–NMR. This led to identification...

Super-resolution imaging of a 2.5 kb non-repetitive DNA in situ in the nuclear genome using molecular beacon probes

Science.gov (United States)

Ni, Yanxiang; Cao, Bo; Ma, Tszshan; Niu, Gang; Huo, Yingdong; Huang, Jiandong; Chen, Danni; Liu, Yi; Yu, Bin; Zhang, Michael Q; Niu, Hanben

2017-01-01

High-resolution visualization of short non-repetitive DNA in situ in the nuclear genome is essential for studying looping interactions and chromatin organization in single cells. Recent advances in fluorescence in situ hybridization (FISH) using Oligopaint probes have enabled super-resolution imaging of genomic domains with a resolution limit of 4.9 kb. To target shorter elements, we developed a simple FISH method that uses molecular beacon (MB) probes to facilitate the probe-target binding, while minimizing non-specific fluorescence. We used three-dimensional stochastic optical reconstruction microscopy (3D-STORM) with optimized imaging conditions to efficiently distinguish sparsely distributed Alexa-647 from background cellular autofluorescence. Utilizing 3D-STORM and only 29–34 individual MB probes, we observed 3D fine-scale nanostructures of 2.5 kb integrated or endogenous unique DNA in situ in human or mouse genome, respectively. We demonstrated our MB-based FISH method was capable of visualizing the so far shortest non-repetitive genomic sequence in 3D at super-resolution. DOI: http://dx.doi.org/10.7554/eLife.21660.001 PMID:28485713

Genome-wide profiling of DNA-binding proteins using barcode-based multiplex Solexa sequencing.

Science.gov (United States)

Raghav, Sunil Kumar; Deplancke, Bart

2012-01-01

Chromatin immunoprecipitation (ChIP) is a commonly used technique to detect the in vivo binding of proteins to DNA. ChIP is now routinely paired to microarray analysis (ChIP-chip) or next-generation sequencing (ChIP-Seq) to profile the DNA occupancy of proteins of interest on a genome-wide level. Because ChIP-chip introduces several biases, most notably due to the use of a fixed number of probes, ChIP-Seq has quickly become the method of choice as, depending on the sequencing depth, it is more sensitive, quantitative, and provides a greater binding site location resolution. With the ever increasing number of reads that can be generated per sequencing run, it has now become possible to analyze several samples simultaneously while maintaining sufficient sequence coverage, thus significantly reducing the cost per ChIP-Seq experiment. In this chapter, we provide a step-by-step guide on how to perform multiplexed ChIP-Seq analyses. As a proof-of-concept, we focus on the genome-wide profiling of RNA Polymerase II as measuring its DNA occupancy at different stages of any biological process can provide insights into the gene regulatory mechanisms involved. However, the protocol can also be used to perform multiplexed ChIP-Seq analyses of other DNA-binding proteins such as chromatin modifiers and transcription factors.

Aircraft micro-doppler feature extraction from high range resolution profiles

CSIR Research Space (South Africa)

Berndt, RJ

2015-10-01

Full Text Available The use of high range resolution measurements and the micro-Doppler effect produced by rotating or vibrating parts of a target has been well documented. This paper presents a technique for extracting features related to helicopter rotors...

Early experience with formalin-fixed paraffin-embedded (FFPE) based commercial clinical genomic profiling of gliomas-robust and informative with caveats.

Science.gov (United States)

Movassaghi, Masoud; Shabihkhani, Maryam; Hojat, Seyed A; Williams, Ryan R; Chung, Lawrance K; Im, Kyuseok; Lucey, Gregory M; Wei, Bowen; Mareninov, Sergey; Wang, Michael W; Ng, Denise W; Tashjian, Randy S; Magaki, Shino; Perez-Rosendahl, Mari; Yang, Isaac; Khanlou, Negar; Vinters, Harry V; Liau, Linda M; Nghiemphu, Phioanh L; Lai, Albert; Cloughesy, Timothy F; Yong, William H

2017-08-01

Commercial targeted genomic profiling with next generation sequencing using formalin-fixed paraffin embedded (FFPE) tissue has recently entered into clinical use for diagnosis and for the guiding of therapy. However, there is limited independent data regarding the accuracy or robustness of commercial genomic profiling in gliomas. As part of patient care, FFPE samples of gliomas from 71 patients were submitted for targeted genomic profiling to one commonly used commercial vendor, Foundation Medicine. Genomic alterations were determined for the following grades or groups of gliomas; Grade I/II, Grade III, primary glioblastomas (GBMs), recurrent primary GBMs, and secondary GBMs. In addition, FFPE samples from the same patients were independently assessed with conventional methods such as immunohistochemistry (IHC), Quantitative real-time PCR (qRT-PCR), or Fluorescence in situ hybridization (FISH) for three genetic alterations: IDH1 mutations, EGFR amplification, and EGFRvIII expression. A total of 100 altered genes were detected by the aforementioned targeted genomic profiling assay. The number of different genomic alterations was significantly different between the five groups of gliomas and consistent with the literature. CDKN2A/B, TP53, and TERT were the most common genomic alterations seen in primary GBMs, whereas IDH1, TP53, and PIK3CA were the most common in secondary GBMs. Targeted genomic profiling demonstrated 92.3%-100% concordance with conventional methods. The targeted genomic profiling report provided an average of 5.5 drugs, and listed an average of 8.4 clinical trials for the 71 glioma patients studied but only a third of the trials were appropriate for glioma patients. In this limited comparison study, this commercial next generation sequencing based-targeted genomic profiling showed a high concordance rate with conventional methods for the 3 genetic alterations and identified mutations expected for the type of glioma. While it may not be feasible to

A high-resolution view of genome-wide pneumococcal transformation.

Directory of Open Access Journals (Sweden)

Nicholas J Croucher

Full Text Available Transformation is an important mechanism of microbial evolution through which bacteria have been observed to rapidly adapt in response to clinical interventions; examples include facilitating vaccine evasion and the development of penicillin resistance in the major respiratory pathogen Streptococcus pneumoniae. To characterise the process in detail, the genomes of 124 S. pneumoniae isolates produced through in vitro transformation were sequenced and recombination events detected. Those recombinations importing the selected marker were independent of unselected events elsewhere in the genome, the positions of which were not significantly affected by local sequence similarity between donor and recipient or mismatch repair processes. However, both types of recombinations were sometimes mosaic, with multiple non-contiguous segments originating from the same molecule of donor DNA. The lengths of the unselected events were exponentially distributed with a mean of 2.3 kb, implying that recombinations are stochastically resolved with a fixed per base probability of 4.4×10(-4 bp(-1. This distribution of recombination sizes, coupled with an observed under representation of large insertions within transferred sequence, suggests transformation has the potential to reduce the size of bacterial genomes, and is unlikely to act as an efficient mechanism for the uptake of accessory genomic loci.

Eocene Antarctic seasonality inferred from high-resolution stable isotope profiles of fossil bivalves and driftwood

Science.gov (United States)

Judd, E. J.; Ivany, L. C.; Miklus, N. M.; Uveges, B. T.; Junium, C. K.

2017-12-01

The Eocene Epoch was a time of large-scale global climate change, experiencing both the warmest temperatures of the Cenozoic and the onset of southern hemisphere glaciation. The record of average global temperatures throughout this transition is reasonably well constrained, however considerably less is known about the accompanying changes in seasonality. Seasonally resolved temperature data provide a wealth of information not readily available from mean annual temperature data alone. These data are particularly important in the climatically sensitive high latitudes, as they can elucidate the means by which climate changes and the conditions necessary for the growth of ice sheets. Several recent studies, however, have suggested the potential for monsoonal precipitation regimes in the early-middle Eocene high latitudes, which complicates interpretation of seasonally resolved oxygen isotope records in shallow nearshore marine settings. Seasonal precipitation and runoff could create a brackish, isotopically depleted lens in these environments, depleting summertime δ18Ocarb and thereby inflating the inferred mean and range of isotope-derived temperatures. Here, we assess intra-annual variations in temperature in shallow nearshore Antarctic waters during the middle and late Eocene, inferred from high-resolution oxygen isotope profiles from accretionary bivalves of the La Meseta Formation, Seymour Island, Antarctica. To address concerns related to precipitation and runoff, we also subsample exceptionally preserved fossil driftwood from within the formation and use seasonal differences in δ13Corg values to estimate the ratio of summertime to wintertime precipitation. Late Eocene oxygen isotope profiles exhibit strongly attenuated seasonal amplitudes and more enriched mean annual values in comparison with data from the middle Eocene. Preliminary fossil wood data are not indicative of a strongly seasonal precipitation regime, implying that intra-annual variation in oxygen

Effects of DTM resolution on slope steepness and soil loss prediction on hillslope profiles

Science.gov (United States)

Eder Paulo Moreira; William J. Elliot; Andrew T. Hudak

2011-01-01

Topographic attributes play a critical role in predicting erosion in models such as the Water Erosion Prediction Project (WEPP). The effects of four different high resolution hillslope profiles were studied using four different DTM resolutions: 1-m, 3-m, 5-m and 10-m. The WEPP model used a common scenario encountered in the forest environment and the selected hillslope...

PanCoreGen – profiling, detecting, annotating protein-coding genes in microbial genomes

Science.gov (United States)

Bhardwaj, Archana; Bag, Sumit K; Sokurenko, Evgeni V.

2015-01-01

A large amount of genomic data, especially from multiple isolates of a single species, has opened new vistas for microbial genomics analysis. Analyzing pan-genome (i.e. the sum of genetic repertoire) of microbial species is crucial in understanding the dynamics of molecular evolution, where virulence evolution is of major interest. Here we present PanCoreGen – a standalone application for pan- and core-genomic profiling of microbial protein-coding genes. PanCoreGen overcomes key limitations of the existing pan-genomic analysis tools, and develops an integrated annotation-structure for species-specific pan-genomic profile. It provides important new features for annotating draft genomes/contigs and detecting unidentified genes in annotated genomes. It also generates user-defined group-specific datasets within the pan-genome. Interestingly, analyzing an example-set of Salmonella genomes, we detect potential footprints of adaptive convergence of horizontally transferred genes in two human-restricted pathogenic serovars – Typhi and Paratyphi A. Overall, PanCoreGen represents a state-of-the-art tool for microbial phylogenomics and pathogenomics study. PMID:26456591

Metabolic profiling of five flavonoids from Dragon's Blood in human liver microsomes using high-performance liquid chromatography coupled with high resolution mass spectrometry.

Science.gov (United States)

Li, Yujuan; Zhang, Yushi; Wang, Rui; Wei, Lizhong; Deng, Yulin; Ren, Wei

2017-05-01

Although much is known about the pharmacological activities of Dragon's Blood (DB, a traditional Chinese herb), its metabolism in human liver microsomes (HLMs) and the cytochrome P450 (CYP) enzymes has not been studied. This study aims to identify the metabolic profile of five flavonoids (loureirin A, loureirin B, loureirin C, 7,4'-dihydroxyflavone and 5,7,4'-trihydroxyflavanone) from DB in HLMs as well as the CYP enzymes that are involved in the metabolism of them. High-resolution mass spectrometry was used to characterize the structures of their metabolites and 10 cDNA-expressed CYP enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) were used to verify which isozymes mediate in the metabolism of the metabolites. Totally, 29 metabolites including 10 metabolites of loureirin A, 10 metabolites of loureirin B, 4 metabolites of loureirin C, 2 metabolites of 7,4'-dihydroxyflavone and 3 metabolites of 5,7,4'-trihydroxyflavanone were elucidated and identified on the basis of the high-resolution MS n data. The metabolic profile of the five flavonoids in HLMs involved hydroxylation, oxidation and demethylation. Among them, hydroxylation was the predominant biotransformation of the five flavonoids in HLMs, occurring in combination with other metabolic reactions. Assay with recombinant P450s revealed that CYP2C9 and CYP2C19 played an important role in the hydroxylation of flavonoids in HLMs. To the best of our knowledge, this is the first in vitro evaluation of the metabolic profile of loureirin A, loureirin B, loureirin C, 7,4'-dihydroxyflavone and 5,7,4'-trihydroxyflavanone in HLMs. Copyright © 2017 Elsevier B.V. All rights reserved.

Whole genome transcription profiling of Anaplasma phagocytophilum in human and tick host cells by tiling array analysis

Directory of Open Access Journals (Sweden)

Chavez Adela

2008-07-01

Full Text Available Abstract Background Anaplasma phagocytophilum (Ap is an obligate intracellular bacterium and the agent of human granulocytic anaplasmosis, an emerging tick-borne disease. Ap alternately infects ticks and mammals and a variety of cell types within each. Understanding the biology behind such versatile cellular parasitism may be derived through the use of tiling microarrays to establish high resolution, genome-wide transcription profiles of the organism as it infects cell lines representative of its life cycle (tick; ISE6 and pathogenesis (human; HL-60 and HMEC-1. Results Detailed, host cell specific transcriptional behavior was revealed. There was extensive differential Ap gene transcription between the tick (ISE6 and the human (HL-60 and HMEC-1 cell lines, with far fewer differentially transcribed genes between the human cell lines, and all disproportionately represented by membrane or surface proteins. There were Ap genes exclusively transcribed in each cell line, apparent human- and tick-specific operons and paralogs, and anti-sense transcripts that suggest novel expression regulation processes. Seven virB2 paralogs (of the bacterial type IV secretion system showed human or tick cell dependent transcription. Previously unrecognized genes and coding sequences were identified, as were the expressed p44/msp2 (major surface proteins paralogs (of 114 total, through elevated signal produced to the unique hypervariable region of each – 2/114 in HL-60, 3/114 in HMEC-1, and none in ISE6. Conclusion Using these methods, whole genome transcription profiles can likely be generated for Ap, as well as other obligate intracellular organisms, in any host cells and for all stages of the cell infection process. Visual representation of comprehensive transcription data alongside an annotated map of the genome renders complex transcription into discernable patterns.

Depth resolution and preferential sputtering in depth profiling of sharp interfaces

International Nuclear Information System (INIS)

Hofmann, S.; Han, Y.S.; Wang, J.Y.

2017-01-01

Highlights: • Interfacial depth resolution from MRI model depends on sputtering rate differences. • Depth resolution critically depends on the dominance of roughness or atomic mixing. • True (depth scale) and apparent (time scale) depth resolutions are different. • Average sputtering rate approximately yields true from apparent depth resolution. • Profiles by SIMS and XPS are different but similar to surface concentrations. - Abstract: The influence of preferential sputtering on depth resolution of sputter depth profiles is studied for different sputtering rates of the two components at an A/B interface. Surface concentration and intensity depth profiles on both the sputtering time scale (as measured) and the depth scale are obtained by calculations with an extended Mixing-Roughness-Information depth (MRI)-model. The results show a clear difference for the two extreme cases (a) preponderant roughness and (b) preponderant atomic mixing. In case (a), the interface width on the time scale (Δt(16–84%)) increases with preferential sputtering if the faster sputtering component is on top of the slower sputtering component, but the true resolution on the depth scale (Δz(16–84%)) stays constant. In case (b), the interface width on the time scale stays constant but the true resolution on the depth scale varies with preferential sputtering. For similar order of magnitude of the atomic mixing and the roughness parameters, a transition state between the two extremes is obtained. While the normalized intensity profile of SIMS represents that of the surface concentration, an additional broadening effect is encountered in XPS or AES by the influence of the mean electron escape depth which may even cause an additional matrix effect at the interface.

Depth resolution and preferential sputtering in depth profiling of sharp interfaces

Energy Technology Data Exchange (ETDEWEB)

Hofmann, S. [Max Planck Institute for Intelligent Systems (formerly MPI for Metals Research), Heisenbergstrasse 3, D-70569 Stuttgart (Germany); Han, Y.S. [Department of Physics, Shantou University, 243 Daxue Road, Shantou, 515063 Guangdong (China); Wang, J.Y., E-mail: wangjy@stu.edu.cn [Department of Physics, Shantou University, 243 Daxue Road, Shantou, 515063 Guangdong (China)

2017-07-15

Highlights: • Interfacial depth resolution from MRI model depends on sputtering rate differences. • Depth resolution critically depends on the dominance of roughness or atomic mixing. • True (depth scale) and apparent (time scale) depth resolutions are different. • Average sputtering rate approximately yields true from apparent depth resolution. • Profiles by SIMS and XPS are different but similar to surface concentrations. - Abstract: The influence of preferential sputtering on depth resolution of sputter depth profiles is studied for different sputtering rates of the two components at an A/B interface. Surface concentration and intensity depth profiles on both the sputtering time scale (as measured) and the depth scale are obtained by calculations with an extended Mixing-Roughness-Information depth (MRI)-model. The results show a clear difference for the two extreme cases (a) preponderant roughness and (b) preponderant atomic mixing. In case (a), the interface width on the time scale (Δt(16–84%)) increases with preferential sputtering if the faster sputtering component is on top of the slower sputtering component, but the true resolution on the depth scale (Δz(16–84%)) stays constant. In case (b), the interface width on the time scale stays constant but the true resolution on the depth scale varies with preferential sputtering. For similar order of magnitude of the atomic mixing and the roughness parameters, a transition state between the two extremes is obtained. While the normalized intensity profile of SIMS represents that of the surface concentration, an additional broadening effect is encountered in XPS or AES by the influence of the mean electron escape depth which may even cause an additional matrix effect at the interface.

Ultra high-resolution gene centric genomic structural analysis of a non-syndromic congenital heart defect, Tetralogy of Fallot.

Directory of Open Access Journals (Sweden)

Douglas C Bittel

Full Text Available Tetralogy of Fallot (TOF is one of the most common severe congenital heart malformations. Great progress has been made in identifying key genes that regulate heart development, yet approximately 70% of TOF cases are sporadic and nonsyndromic with no known genetic cause. We created an ultra high-resolution gene centric comparative genomic hybridization (gcCGH microarray based on 591 genes with a validated association with cardiovascular development or function. We used our gcCGH array to analyze the genomic structure of 34 infants with sporadic TOF without a deletion on chromosome 22q11.2 (n male = 20; n female = 14; age range of 2 to 10 months. Using our custom-made gcCGH microarray platform, we identified a total of 613 copy number variations (CNVs ranging in size from 78 base pairs to 19.5 Mb. We identified 16 subjects with 33 CNVs that contained 13 different genes which are known to be directly associated with heart development. Additionally, there were 79 genes from the broader list of genes that were partially or completely contained in a CNV. All 34 individuals examined had at least one CNV involving these 79 genes. Furthermore, we had available whole genome exon arrays from right ventricular tissue in 13 of our subjects. We analyzed these for correlations between copy number and gene expression level. Surprisingly, we could detect only one clear association between CNVs and expression (GSTT1 for any of the 591 focal genes on the gcCGH array. The expression levels of GSTT1 were correlated with copy number in all cases examined (r = 0.95, p = 0.001. We identified a large number of small CNVs in genes with varying associations with heart development. Our results illustrate the complexity of human genome structural variation and underscore the need for multifactorial assessment of potential genetic/genomic factors that contribute to congenital heart defects.

Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

Science.gov (United States)

Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

2013-01-01

In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

Profiling of modified nucleosides from ribonucleic acid digestion by supercritical fluid chromatography coupled to high resolution mass spectrometry.

Science.gov (United States)

Laboureur, Laurent; Guérineau, Vincent; Auxilien, Sylvie; Yoshizawa, Satoko; Touboul, David

2018-02-16

A method based on supercritical fluid chromatography coupled to high resolution mass spectrometry for the profiling of canonical and modified nucleosides was optimized, and compared to classical reverse-phase liquid chromatography in terms of separation, number of detected modified nucleosides and sensitivity. Limits of detection and quantification were measured using statistical method and quantifications of twelve nucleosides of a tRNA digest from E. coli are in good agreement with previously reported data. Results highlight the complementarity of both separation techniques to cover the largest view of nucleoside modifications for forthcoming epigenetic studies. Copyright © 2017 Elsevier B.V. All rights reserved.

High-resolution metagenomics targets major functional types in complex microbial communities

Energy Technology Data Exchange (ETDEWEB)

Kalyuzhnaya, Marina G.; Lapidus, Alla; Ivanova, Natalia; Copeland, Alex C.; McHardy, Alice C.; Szeto, Ernest; Salamov, Asaf; Grigoriev, Igor V.; Suciu, Dominic; Levine, Samuel R.; Markowitz, Victor M.; Rigoutsos, Isidore; Tringe, Susannah G.; Bruce, David C.; Richardson, Paul M.; Lidstrom, Mary E.; Chistoserdova, Ludmila

2009-08-01

Most microbes in the biosphere remain uncultured and unknown. Whole genome shotgun (WGS) sequencing of environmental DNA (metagenomics) allows glimpses into genetic and metabolic potentials of natural microbial communities. However, in communities of high complexity metagenomics fail to link specific microbes to specific ecological functions. To overcome this limitation, we selectively targeted populations involved in oxidizing single-carbon (C{sub 1}) compounds in Lake Washington (Seattle, USA) by labeling their DNA via stable isotope probing (SIP), followed by WGS sequencing. Metagenome analysis demonstrated specific sequence enrichments in response to different C{sub 1} substrates, highlighting ecological roles of individual phylotypes. We further demonstrated the utility of our approach by extracting a nearly complete genome of a novel methylotroph Methylotenera mobilis, reconstructing its metabolism and conducting genome-wide analyses. This approach allowing high-resolution genomic analysis of ecologically relevant species has the potential to be applied to a wide variety of ecosystems.

Non-targeted glycosidic profiling of international wines using neutral loss-high resolution mass spectrometry.

Science.gov (United States)

Barnaba, C; Dellacassa, E; Nicolini, G; Nardin, T; Serra, M; Larcher, R

2018-07-06

Many metabolites naturally occur as glycosides, since sugar moieties can be crucial for their biological activity and increase their water solubility. In the plant kingdom they may occur as glycosides or sugar esters, depending on precursor chemical structure, and in wine they have traditionally attracted attention due to their organoleptic properties, such as astringency and bitterness, and because they affect the colour and aroma of wines. A new approach directed at detailed description of glycosides in a large selection of monovarietal wines (8 samples each of Pinot Blanc, Muller Thurgau, Riesling, Traminer, Merlot, Pinot Noir and Cabernet Sauvignon) was developed by combining high performance liquid chromatography with high resolution tandem mass spectrometry. Analytical separation was performed on an Accucore™ Polar Premium LC column, while mass analysis was performed in negative ion mode with an non-targeted screening approach, using a Full MS/AIF/NL dd-MS 2 experiment at a resolving power of 140,000 FWHM. Over 280 glycoside-like compounds were detected, of which 133 (including low-molecular weight phenols, flavonoids and monoterpenols) were tentatively identified in the form of pentose (6), deoxyhexose (17), hexose (73), hexose-pentose (16), hexose-deoxyhexose (7), dihexose (5) and hexose ester (9) derivatives. It was not possible to univocally define the corresponding chemical structure for the remaining 149 glycosides. Non-parametric statistical analysis showed it was possible to well characterise the glycosylated profile of all red and Traminer wines, while the identified glycosides were almost entirely lacking in Pinot Blanc, Riesling and Muller Thurgau wines. Also Tukey's Honestly Significant Difference test (p wines from each other according to their glycosylated profile. Copyright © 2018 Elsevier B.V. All rights reserved.

1H High Resolution Magic-Angle Coil Spinning (HR-MACS µNMR Metabolic Profiling of whole Saccharomyces cervisiae cells: A Demonstrative Study

Directory of Open Access Journals (Sweden)

Alan eWong

2014-06-01

Full Text Available The low sensitivity of Nuclear Magnetic Resonance (NMR is its prime shortcoming compared to other analytical methods for metabolomic studies. It relies on large sample volume (30–50 µl for HR-MAS for rich metabolic profiling, hindering high-throughput screening especially when the sample requires a labor-intensive preparation or is a sacred specimen. This is indeed the case for some living organisms. This study evaluates a 1H HR-MAS approach for metabolic profiling of small volume (250 nl whole bacterial cells, Saccharomyces cervisiae, using an emerging micro-NMR technology: high-resolution magic-angle coil spinning (HR-MACS. As a demonstrative study for whole cells, we perform two independent metabolomics studies identifying the significant metabolites associated with osmotic stress and aging.

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues

International Nuclear Information System (INIS)

Cifola, Ingrid; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A

2011-01-01

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

A high resolution, single bunch, beam profile monitor

International Nuclear Information System (INIS)

Norem, J.

1992-01-01

Efficient linear colliders require very small beam spots to produce high luminosities with reasonable input power, which limits the number of electrons which can be accelerated to high energies. The small beams, in turn, require high precision and stability in all accelerator components. Producing, monitoring and maintaining beams of the required quality has been, and will continue to be, difficult. A beam monitoring system which could be used to measure beam profile, size and stability at the final focus of a beamline or collider has been developed and is described here. The system uses nonimaging bremsstrahlung optics. The immediate use for this system would be examining the final focus spot at the SLAC/FFTB. The primary alternatives to this technique are those proposed by P. Chen / J. Buon, which analyses the energy and angular distributions of ion recoils to determine the aspect ratio of the electron bunch, and a method proposed by Shintake, which measures intensity variation of compton backscattered photons as the beam is moved across a pattern of standing waves produced by a laser

Soybean (Glycine max) SWEET gene family: insights through comparative genomics, transcriptome profiling and whole genome re-sequence analysis.

Science.gov (United States)

Patil, Gunvant; Valliyodan, Babu; Deshmukh, Rupesh; Prince, Silvas; Nicander, Bjorn; Zhao, Mingzhe; Sonah, Humira; Song, Li; Lin, Li; Chaudhary, Juhi; Liu, Yang; Joshi, Trupti; Xu, Dong; Nguyen, Henry T

2015-07-11

SWEET (MtN3_saliva) domain proteins, a recently identified group of efflux transporters, play an indispensable role in sugar efflux, phloem loading, plant-pathogen interaction and reproductive tissue development. The SWEET gene family is predominantly studied in Arabidopsis and members of the family are being investigated in rice. To date, no transcriptome or genomics analysis of soybean SWEET genes has been reported. In the present investigation, we explored the evolutionary aspect of the SWEET gene family in diverse plant species including primitive single cell algae to angiosperms with a major emphasis on Glycine max. Evolutionary features showed expansion and duplication of the SWEET gene family in land plants. Homology searches with BLAST tools and Hidden Markov Model-directed sequence alignments identified 52 SWEET genes that were mapped to 15 chromosomes in the soybean genome as tandem duplication events. Soybean SWEET (GmSWEET) genes showed a wide range of expression profiles in different tissues and developmental stages. Analysis of public transcriptome data and expression profiling using quantitative real time PCR (qRT-PCR) showed that a majority of the GmSWEET genes were confined to reproductive tissue development. Several natural genetic variants (non-synonymous SNPs, premature stop codons and haplotype) were identified in the GmSWEET genes using whole genome re-sequencing data analysis of 106 soybean genotypes. A significant association was observed between SNP-haplogroup and seed sucrose content in three gene clusters on chromosome 6. Present investigation utilized comparative genomics, transcriptome profiling and whole genome re-sequencing approaches and provided a systematic description of soybean SWEET genes and identified putative candidates with probable roles in the reproductive tissue development. Gene expression profiling at different developmental stages and genomic variation data will aid as an important resource for the soybean research

Metagenome Fragment Classification Using -Mer Frequency Profiles

Directory of Open Access Journals (Sweden)

Gail Rosen

2008-01-01

Full Text Available A vast amount of microbial sequencing data is being generated through large-scale projects in ecology, agriculture, and human health. Efficient high-throughput methods are needed to analyze the mass amounts of metagenomic data, all DNA present in an environmental sample. A major obstacle in metagenomics is the inability to obtain accuracy using technology that yields short reads. We construct the unique -mer frequency profiles of 635 microbial genomes publicly available as of February 2008. These profiles are used to train a naive Bayes classifier (NBC that can be used to identify the genome of any fragment. We show that our method is comparable to BLAST for small 25 bp fragments but does not have the ambiguity of BLAST's tied top scores. We demonstrate that this approach is scalable to identify any fragment from hundreds of genomes. It also performs quite well at the strain, species, and genera levels and achieves strain resolution despite classifying ubiquitous genomic fragments (gene and nongene regions. Cross-validation analysis demonstrates that species-accuracy achieves 90% for highly-represented species containing an average of 8 strains. We demonstrate that such a tool can be used on the Sargasso Sea dataset, and our analysis shows that NBC can be further enhanced.

A gene-based high-resolution comparative radiation hybrid map as a framework for genome sequence assembly of a bovine chromosome 6 region associated with QTL for growth, body composition, and milk performance traits

Directory of Open Access Journals (Sweden)

Laurent Pascal

2006-03-01

Full Text Available Abstract Background A number of different quantitative trait loci (QTL for various phenotypic traits, including milk production, functional, and conformation traits in dairy cattle as well as growth and body composition traits in meat cattle, have been mapped consistently in the middle region of bovine chromosome 6 (BTA6. Dense genetic and physical maps and, ultimately, a fully annotated genome sequence as well as their mutual connections are required to efficiently identify genes and gene variants responsible for genetic variation of phenotypic traits. A comprehensive high-resolution gene-rich map linking densely spaced bovine markers and genes to the annotated human genome sequence is required as a framework to facilitate this approach for the region on BTA6 carrying the QTL. Results Therefore, we constructed a high-resolution radiation hybrid (RH map for the QTL containing chromosomal region of BTA6. This new RH map with a total of 234 loci including 115 genes and ESTs displays a substantial increase in loci density compared to existing physical BTA6 maps. Screening the available bovine genome sequence resources, a total of 73 loci could be assigned to sequence contigs, which were already identified as specific for BTA6. For 43 loci, corresponding sequence contigs, which were not yet placed on the bovine genome assembly, were identified. In addition, the improved potential of this high-resolution RH map for BTA6 with respect to comparative mapping was demonstrated. Mapping a large number of genes on BTA6 and cross-referencing them with map locations in corresponding syntenic multi-species chromosome segments (human, mouse, rat, dog, chicken achieved a refined accurate alignment of conserved segments and evolutionary breakpoints across the species included. Conclusion The gene-anchored high-resolution RH map (1 locus/300 kb for the targeted region of BTA6 presented here will provide a valuable platform to guide high-quality assembling and

High resolution beam profiling of X-ray free electron laser radiation by polymer imprint development.

Science.gov (United States)

Rösner, Benedikt; Döring, Florian; Ribič, Primož R; Gauthier, David; Principi, Emiliano; Masciovecchio, Claudio; Zangrando, Marco; Vila-Comamala, Joan; De Ninno, Giovanni; David, Christian

2017-11-27

High resolution metrology of beam profiles is presently a major challenge at X-ray free electron lasers. We demonstrate a characterization method based on beam imprints in poly (methyl methacrylate). By immersing the imprints formed at 47.8 eV into organic solvents, the regions exposed to the beam are removed similar to resist development in grayscale lithography. This allows for extending the sensitivity of the method by more than an order of magnitude compared to the established analysis of imprints created solely by ablation. Applying the Beer-Lambert law for absorption, the intensity distribution in a micron-sized focus can be reconstructed from one single shot with a high dynamic range, exceeding 10 3 . The procedure described here allows for beam characterization at free electron lasers revealing even faint beam tails, which are not accessible when using ablation imprint methods. We demonstrate the greatly extended dynamic range on developed imprints taken in focus of conventional Fresnel zone plates and spiral zone plates producing beams with a topological charge.

Combined use of high-resolution α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR for investigation of antidiabetic principles in crude plant extracts

DEFF Research Database (Denmark)

Kongstad, Kenneth Thermann; Özdemir, Ceylan; Barzak, Asmah

2015-01-01

Type 2 diabetes is a metabolic disorder affecting millions of people worldwide, and new drug leads or functional foods containing selective α-glucosidase inhibitors are needed. Crude extract of 24 plants were assessed for α-glucosidase inhibitory activity. Methanol extracts of Cinnamomum zeylanicum...... bark, Rheum rhabarbarum peel, and Rheum palmatum root and ethyl acetate extracts of C. zeylanicum bark, Allium ascalonicum peel, and R. palmatum root showed IC50 values below 20 μg/mL. Subsequently, high-resolution α-glucosidase profiling was used in combination with high-performance liquid...... chromatography–high-resolution mass spectrometry–solid-phase extraction–nuclear magnetic resonance spectroscopy for identification of metabolites responsible for the α-glucosidase inhibitory activity. Quercetin (1) and its dimer (2), trimer (3), and tetramer (4) were identified as main α-glucosidase inhibitors...

Integrated high-resolution array CGH and SKY analysis of homozygous deletions and other genomic alterations present in malignant mesothelioma cell lines.

Science.gov (United States)

Klorin, Geula; Rozenblum, Ester; Glebov, Oleg; Walker, Robert L; Park, Yoonsoo; Meltzer, Paul S; Kirsch, Ilan R; Kaye, Frederic J; Roschke, Anna V

2013-05-01

High-resolution oligonucleotide array comparative genomic hybridization (aCGH) and spectral karyotyping (SKY) were applied to a panel of malignant mesothelioma (MMt) cell lines. SKY has not been applied to MMt before, and complete karyotypes are reported based on the integration of SKY and aCGH results. A whole genome search for homozygous deletions (HDs) produced the largest set of recurrent and non-recurrent HDs for MMt (52 recurrent HDs in 10 genomic regions; 36 non-recurrent HDs). For the first time, LINGO2, RBFOX1/A2BP1, RPL29, DUSP7, and CCSER1/FAM190A were found to be homozygously deleted in MMt, and some of these genes could be new tumor suppressor genes for MMt. Integration of SKY and aCGH data allowed reconstruction of chromosomal rearrangements that led to the formation of HDs. Our data imply that only with acquisition of structural and/or numerical karyotypic instability can MMt cells attain a complete loss of tumor suppressor genes located in 9p21.3, which is the most frequently homozygously deleted region. Tetraploidization is a late event in the karyotypic progression of MMt cells, after HDs in the 9p21.3 region have already been acquired. Published by Elsevier Inc.

Initial results of high resolution L-H transition studies on DIII-D

International Nuclear Information System (INIS)

Wang, G; Rhodes, T L; Doyle, E J; Peebles, W A; Zeng, L; Burrell, K H; McKee, G R; Groebner, R J; Evans, T E

2004-01-01

Understanding the L-H transition in tokamaks has been an important area of research for more than two decades. High time resolution diagnostics on DIII-D allow detailed characterization of the L-H transition and, therefore, testing and benchmarking of theoretical models. An experiment was performed in DIII-D utilizing a novel, high temporal and spatial resolution reflectometer density profile system to measure densities from the SOL to the inside separatrix. Initial data analysis indicates different density profile evolution during L-H transitions in upper single-null and lower single-null divertor configuration plasmas. A detailed comparison of the density gradient and fluctuation changes is presented for these two cases

Initial results of high resolution L-H transition studies on DIII-D

Energy Technology Data Exchange (ETDEWEB)

Wang, G [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Rhodes, T L [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Doyle, E J [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Peebles, W A [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Zeng, L [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Burrell, K H [General Atomics, PO Box 85608, San Diego, CA 92186 (United States); McKee, G R [University of Wisconsin-Madison, 1500 Engineering Drive, Madison, WI 53706 (United States); Groebner, R J [General Atomics, PO Box 85608, San Diego, CA 92186 (United States); Evans, T E [General Atomics, PO Box 85608, San Diego, CA 92186 (United States)

2004-05-01

Understanding the L-H transition in tokamaks has been an important area of research for more than two decades. High time resolution diagnostics on DIII-D allow detailed characterization of the L-H transition and, therefore, testing and benchmarking of theoretical models. An experiment was performed in DIII-D utilizing a novel, high temporal and spatial resolution reflectometer density profile system to measure densities from the SOL to the inside separatrix. Initial data analysis indicates different density profile evolution during L-H transitions in upper single-null and lower single-null divertor configuration plasmas. A detailed comparison of the density gradient and fluctuation changes is presented for these two cases.

High Resolution Infrared Radiation Sounder (HIRS) for the Nimbus F Spacecraft

Science.gov (United States)

Koenig, E. W.

1975-01-01

Flown on Nimbus F in June 1975, the high resolution infrared radiation sounder (HIRS) scans with a geographical resolution of 23KM and samples radiance in seventeen selected spectral channels from visible (.7 micron) to far IR (15 micron). Vertical temperature profiles and atmospheric moisture content can be inferred from the output. System operation and test results are described.

Get your high-quality low-cost genome sequence

NARCIS (Netherlands)

Faino, L.; Thomma, B.P.H.J.

2014-01-01

The study of whole-genome sequences has become essential for almost all branches of biological research. Next-generation sequencing (NGS) has revolutionized the scalability, speed, and resolution of sequencing and brought genomic science within reach of academic laboratories that study non-model

Narrow nuclear resonance profiling of Al with subnanometric depth resolution

International Nuclear Information System (INIS)

Rosa, E.B.O. da; Krug, C.; Stedile, F.C.; Morais, J.; Baumvol, I.J.R.

2002-01-01

We report on the use of the narrow and isolated resonance at 404.9 keV in the cross-section curve of the 27 Al(p,γ) 28 Si nuclear reaction for profiling Al in ultrathin aluminum oxide films on Si. The samples were characterized as-deposited and after thermal annealing, so that Al transport could be studied. An estimated depth resolution of approximately 0.4 nm near the surface of the films could be obtained owing to: (i) the very small resonance width; (ii) the high stopping power of Al 2 O 3 for 404.9 keV protons; (iii) the high energy stability of the proton beam provided by the 500 kV HVEE ion implanter at Porto Alegre; and (iv) an apparent thickness magnification by a factor between 2.0 and 2.4 with the use of glancing incidence. This technique is compared to other methods for Al profiling like medium energy ion scattering and some sputtering-based techniques

High resolution 10Be and 230Th profiles in DSDP site 580

International Nuclear Information System (INIS)

Eisenhauer, A.; Mangini, A.; Segl, M.; Beer, J.; Bonani, G.; Suter, M.; Woelfli, W.

1987-01-01

10 Be and 230 Th profiles were measured at Site 580 at a depth of 20 m ( 230 Th and 10 Be) and 80 m ( 10 Be), corresponding to 360 ka and 1.5 Ma, respectively, with a resolution of approx. 5000 a. The radiometric sediment accumulation rates of 6.2 cm/ka (±25%) agree well with the average for the last 730 ka (via paleomagnetic stratigraphy). Age corrected concentrations of 10 Be range from 2 to 7x10 9 atoms/g (average 3.5±1). The variations of the 10 Be concentrations can be explained by changes in the sediment supply during different climatic conditions. The maxima and the minima of 10 Be follow the fluctuations of excess 230 Th in the core section during the last 360 ka. Fluxes of both 10 Be and 230 Th exceed production and vary remarkably throughout time suggesting enhanced scavenging by bioproductivity. At the Brunhess-Matuyama boundary we observe a maximum of 10 Be (6.0±0.3x10 9 atoms/g, corresponding to 2.5 σ deviation from the average value). However, the observed large fluctuations of Be-10 throughout the core profile make it difficult to interprete this particular maximum. (orig.)

CGDM: collaborative genomic data model for molecular profiling data using NoSQL.

Science.gov (United States)

Wang, Shicai; Mares, Mihaela A; Guo, Yi-Ke

2016-12-01

High-throughput molecular profiling has greatly improved patient stratification and mechanistic understanding of diseases. With the increasing amount of data used in translational medicine studies in recent years, there is a need to improve the performance of data warehouses in terms of data retrieval and statistical processing. Both relational and Key Value models have been used for managing molecular profiling data. Key Value models such as SeqWare have been shown to be particularly advantageous in terms of query processing speed for large datasets. However, more improvement can be achieved, particularly through better indexing techniques of the Key Value models, taking advantage of the types of queries which are specific for the high-throughput molecular profiling data. In this article, we introduce a Collaborative Genomic Data Model (CGDM), aimed at significantly increasing the query processing speed for the main classes of queries on genomic databases. CGDM creates three Collaborative Global Clustering Index Tables (CGCITs) to solve the velocity and variety issues at the cost of limited extra volume. Several benchmarking experiments were carried out, comparing CGDM implemented on HBase to the traditional SQL data model (TDM) implemented on both HBase and MySQL Cluster, using large publicly available molecular profiling datasets taken from NCBI and HapMap. In the microarray case, CGDM on HBase performed up to 246 times faster than TDM on HBase and 7 times faster than TDM on MySQL Cluster. In single nucleotide polymorphism case, CGDM on HBase outperformed TDM on HBase by up to 351 times and TDM on MySQL Cluster by up to 9 times. The CGDM source code is available at https://github.com/evanswang/CGDM. y.guo@imperial.ac.uk. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ultra high resolution SFC-MS as a high throughput platform for metabolic phenotyping: application to metabolic profiling of rat and dog bile.

Science.gov (United States)

Jones, Michael D; Rainville, Paul D; Isaac, Giorgis; Wilson, Ian D; Smith, Norman W; Plumb, Robert S

2014-09-01

Ultra high resolution SFC-MS (on sub-2μm particles) coupled to mass spectrometry has been evaluated for the metabolic profiling of rat and dog bile. The selectivity of the SFC separation differed from that seen in previous reversed-phase UPLC-MS studies on bile, with the order of elution for analytes such as e.g., the bile acids showing many differences. The chromatography system showed excellent stability, reproducibility and robustness with relative standard deviation of less than 1% for retention time obtained over the course of the analysis. SFC showed excellent chromatographic performance with chromatographic peak widths in the order of 3s at the base of the peak. The use of supercritical fluid carbon dioxide as a mobile phase solvent also reduced the overall consumption of organic solvent by a factor of 3 and also reduced the overall analysis time by a factor of 30% compared to reversed-phase gradient LC. SFC-MS appear complementary to RPLC for the metabolic profiling of complex samples such as bile. Copyright © 2014 Elsevier B.V. All rights reserved.

Rapid detection and differentiation of Clonorchis sinensis and Opisthorchis viverrini using real-time PCR and high resolution melting analysis.

Science.gov (United States)

Cai, Xian-Quan; Yu, Hai-Qiong; Li, Rong; Yue, Qiao-Yun; Liu, Guo-Hua; Bai, Jian-Shan; Deng, Yan; Qiu, De-Yi; Zhu, Xing-Quan

2014-01-01

Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA extracted from the two flukes yielded specific amplification and their identity was confirmed by sequencing, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1 metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to be differentiated by their HRM profiles. The method can reduce labor of microscopic examination and the contamination of agarose electrophoresis. Moreover, it can differentiate these two flukes which are difficult to be distinguished using other methods. The established method provides an alternative tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini.

Rapid Detection and Differentiation of Clonorchis sinensis and Opisthorchis viverrini Using Real-Time PCR and High Resolution Melting Analysis

Directory of Open Access Journals (Sweden)

Xian-Quan Cai

2014-01-01

Full Text Available Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA extracted from the two flukes yielded specific amplification and their identity was confirmed by sequencing, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1 metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to be differentiated by their HRM profiles. The method can reduce labor of microscopic examination and the contamination of agarose electrophoresis. Moreover, it can differentiate these two flukes which are difficult to be distinguished using other methods. The established method provides an alternative tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini.

An overview on genome organization of marine organisms.

Science.gov (United States)

Costantini, Maria

2015-12-01

In this review we will concentrate on some general genome features of marine organisms and their evolution, ranging from vertebrate to invertebrates until unicellular organisms. Before genome sequencing, the ultracentrifugation in CsCl led to high resolution of mammalian DNA (without seeing at the sequence). The analytical profile of human DNA showed that the vertebrate genome is a mosaic of isochores, typically megabase-size DNA segments that belong in a small number of families characterized by different GC levels. The recent availability of a number of fully sequenced genomes allowed mapping very precisely the isochores, based on DNA sequences. Since isochores are tightly linked to biological properties such as gene density, replication timing and recombination, the new level of detail provided by the isochore map helped the understanding of genome structure, function and evolution. This led the current level of knowledge and to further insights. Copyright © 2015. Published by Elsevier B.V.

High-resolution copy number variation analysis of schizophrenia in Japan.

Science.gov (United States)

Kushima, I; Aleksic, B; Nakatochi, M; Shimamura, T; Shiino, T; Yoshimi, A; Kimura, H; Takasaki, Y; Wang, C; Xing, J; Ishizuka, K; Oya-Ito, T; Nakamura, Y; Arioka, Y; Maeda, T; Yamamoto, M; Yoshida, M; Noma, H; Hamada, S; Morikawa, M; Uno, Y; Okada, T; Iidaka, T; Iritani, S; Yamamoto, T; Miyashita, M; Kobori, A; Arai, M; Itokawa, M; Cheng, M-C; Chuang, Y-A; Chen, C-H; Suzuki, M; Takahashi, T; Hashimoto, R; Yamamori, H; Yasuda, Y; Watanabe, Y; Nunokawa, A; Someya, T; Ikeda, M; Toyota, T; Yoshikawa, T; Numata, S; Ohmori, T; Kunimoto, S; Mori, D; Iwata, N; Ozaki, N

2017-03-01

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

High resolution tsunami inversion for 2010 Chile earthquake

Directory of Open Access Journals (Sweden)

T.-R. Wu

2011-12-01

Full Text Available We investigate the feasibility of inverting high-resolution vertical seafloor displacement from tsunami waveforms. An inversion method named "SUTIM" (small unit tsunami inversion method is developed to meet this goal. In addition to utilizing the conventional least-square inversion, this paper also enhances the inversion resolution by Grid-Shifting method. A smooth constraint is adopted to gain stability. After a series of validation and performance tests, SUTIM is used to study the 2010 Chile earthquake. Based upon data quality and azimuthal distribution, we select tsunami waveforms from 6 GLOSS stations and 1 DART buoy record. In total, 157 sub-faults are utilized for the high-resolution inversion. The resolution reaches 10 sub-faults per wavelength. The result is compared with the distribution of the aftershocks and waveforms at each gauge location with very good agreement. The inversion result shows that the source profile features a non-uniform distribution of the seafloor displacement. The highly elevated vertical seafloor is mainly concentrated in two areas: one is located in the northern part of the epicentre, between 34° S and 36° S; the other is in the southern part, between 37° S and 38° S.

High resolution tsunami inversion for 2010 Chile earthquake

Science.gov (United States)

Wu, T.-R.; Ho, T.-C.

2011-12-01

We investigate the feasibility of inverting high-resolution vertical seafloor displacement from tsunami waveforms. An inversion method named "SUTIM" (small unit tsunami inversion method) is developed to meet this goal. In addition to utilizing the conventional least-square inversion, this paper also enhances the inversion resolution by Grid-Shifting method. A smooth constraint is adopted to gain stability. After a series of validation and performance tests, SUTIM is used to study the 2010 Chile earthquake. Based upon data quality and azimuthal distribution, we select tsunami waveforms from 6 GLOSS stations and 1 DART buoy record. In total, 157 sub-faults are utilized for the high-resolution inversion. The resolution reaches 10 sub-faults per wavelength. The result is compared with the distribution of the aftershocks and waveforms at each gauge location with very good agreement. The inversion result shows that the source profile features a non-uniform distribution of the seafloor displacement. The highly elevated vertical seafloor is mainly concentrated in two areas: one is located in the northern part of the epicentre, between 34° S and 36° S; the other is in the southern part, between 37° S and 38° S.

A high-resolution map of the Nile tilapia genome: a resource for studying cichlids and other percomorphs

Science.gov (United States)

2012-01-01

Background The Nile tilapia (Oreochromis niloticus) is the second most farmed fish species worldwide. It is also an important model for studies of fish physiology, particularly because of its broad tolerance to an array of environments. It is a good model to study evolutionary mechanisms in vertebrates, because of its close relationship to haplochromine cichlids, which have undergone rapid speciation in East Africa. The existing genomic resources for Nile tilapia include a genetic map, BAC end sequences and ESTs, but comparative genome analysis and maps of quantitative trait loci (QTL) are still limited. Results We have constructed a high-resolution radiation hybrid (RH) panel for the Nile tilapia and genotyped 1358 markers consisting of 850 genes, 82 markers corresponding to BAC end sequences, 154 microsatellites and 272 single nucleotide polymorphisms (SNPs). From these, 1296 markers could be associated in 81 RH groups, while 62 were not linked. The total size of the RH map is 34,084 cR3500 and 937,310 kb. It covers 88% of the entire genome with an estimated inter-marker distance of 742 Kb. Mapping of microsatellites enabled integration to the genetic map. We have merged LG8 and LG24 into a single linkage group, and confirmed that LG16-LG21 are also merged. The orientation and association of RH groups to each chromosome and LG was confirmed by chromosomal in situ hybridizations (FISH) of 55 BACs. Fifty RH groups were localized on the 22 chromosomes while 31 remained small orphan groups. Synteny relationships were determined between Nile tilapia, stickleback, medaka and pufferfish. Conclusion The RH map and associated FISH map provide a valuable gene-ordered resource for gene mapping and QTL studies. All genetic linkage groups with their corresponding RH groups now have a corresponding chromosome which can be identified in the karyotype. Placement of conserved segments indicated that multiple inter-chromosomal rearrangements have occurred between Nile tilapia

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

Science.gov (United States)

Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

2011-06-13

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

A comparison of PCR assays for beak and feather disease virus and high resolution melt (HRM) curve analysis of replicase associated protein and capsid genes.

Science.gov (United States)

Das, Shubhagata; Sarker, Subir; Ghorashi, Seyed Ali; Forwood, Jade K; Raidal, Shane R

2016-11-01

Beak and feather disease virus (BFDV) threatens a wide range of endangered psittacine birds worldwide. In this study, we assessed a novel PCR assay and genetic screening method using high-resolution melt (HRM) curve analysis for BFDV targeting the capsid (Cap) gene (HRM-Cap) alongside conventional PCR detection as well as a PCR method that targets a much smaller fragment of the virus genome in the replicase initiator protein (Rep) gene (HRM-Rep). Limits of detection, sensitivity, specificity and discriminatory power for differentiating BFDV sequences were compared. HRM-Cap had a high positive predictive value and could readily differentiate between a reference genotype and 17 other diverse BFDV genomes with more discriminatory power (genotype confidence percentage) than HRM-Rep. Melt curve profiles generated by HRM-Cap correlated with unique DNA sequence profiles for each individual test genome. The limit of detection of HRM-Cap was lower (2×10 -5 ng/reaction or 48 viral copies) than that for both HRM-Rep and conventional BFDV PCR which had similar sensitivity (2×10 -6 ng or 13 viral copies/reaction). However, when used in a diagnostic setting with 348 clinical samples there was strong agreement between HRM-Cap and conventional PCR (kappa=0.87, PHRM-Cap demonstrated higher specificity (99.9%) than HRM-Rep (80.3%). Copyright © 2016 Elsevier B.V. All rights reserved.

Attention-Based Recurrent Temporal Restricted Boltzmann Machine for Radar High Resolution Range Profile Sequence Recognition

Directory of Open Access Journals (Sweden)

Yifan Zhang

2018-05-01

Full Text Available The High Resolution Range Profile (HRRP recognition has attracted great concern in the field of Radar Automatic Target Recognition (RATR. However, traditional HRRP recognition methods failed to model high dimensional sequential data efficiently and have a poor anti-noise ability. To deal with these problems, a novel stochastic neural network model named Attention-based Recurrent Temporal Restricted Boltzmann Machine (ARTRBM is proposed in this paper. RTRBM is utilized to extract discriminative features and the attention mechanism is adopted to select major features. RTRBM is efficient to model high dimensional HRRP sequences because it can extract the information of temporal and spatial correlation between adjacent HRRPs. The attention mechanism is used in sequential data recognition tasks including machine translation and relation classification, which makes the model pay more attention to the major features of recognition. Therefore, the combination of RTRBM and the attention mechanism makes our model effective for extracting more internal related features and choose the important parts of the extracted features. Additionally, the model performs well with the noise corrupted HRRP data. Experimental results on the Moving and Stationary Target Acquisition and Recognition (MSTAR dataset show that our proposed model outperforms other traditional methods, which indicates that ARTRBM extracts, selects, and utilizes the correlation information between adjacent HRRPs effectively and is suitable for high dimensional data or noise corrupted data.

Assessing the influence of the temporal resolution of electrical load and PV generation profiles on self-consumption and sizing of PV-battery systems

International Nuclear Information System (INIS)

Beck, T.; Kondziella, H.; Huard, G.; Bruckner, T.

2016-01-01

Highlights: • MILP optimization model for operation and investment of PV-battery systems. • Use of high resolution (10 s) electrical household load and PV generation profiles. • Analysis of influence of temporal resolution on self-consumption and optimal sizing. • Electrical load profile characteristics influence required temporal resolution. - Abstract: The interest in self-consumption of electricity generated by rooftop photovoltaic systems has grown in recent years, fueled by decreasing levelized costs of electricity and feed-in tariffs as well as increasing end customer electricity prices in the residential sector. This also fostered research on grid-connected PV-battery storage systems, which are a promising technology to increase self-consumption. In this paper a mixed-integer linear optimization model of a PV-battery system that minimizes the total discounted operating and investment costs is developed. The model is employed to study the effect of the temporal resolution of electrical load and PV generation profiles on the rate of self-consumption and the optimal sizing of PV and PV-battery systems. In contrast to previous studies high resolution (10 s) measured input data for both PV generation and electrical load profiles is used for the analysis. The data was obtained by smart meter measurements in 25 different households in Germany. It is shown that the temporal resolution of load profiles is more critical for the accuracy of the determination of self-consumption rates than the resolution of the PV generation. For PV-systems without additional storage accurate results can be obtained by using 15 min solar irradiation data. The required accuracy for the electrical load profiles depends strongly on the load profile characteristics. While good results can be obtained with 60 s for all electrical load profiles, 15 min data can still be sufficient for load profiles that do not exhibit most of their electricity consumption at power levels above 2 k

Single-Cell-Based Platform for Copy Number Variation Profiling through Digital Counting of Amplified Genomic DNA Fragments.

Science.gov (United States)

Li, Chunmei; Yu, Zhilong; Fu, Yusi; Pang, Yuhong; Huang, Yanyi

2017-04-26

We develop a novel single-cell-based platform through digital counting of amplified genomic DNA fragments, named multifraction amplification (mfA), to detect the copy number variations (CNVs) in a single cell. Amplification is required to acquire genomic information from a single cell, while introducing unavoidable bias. Unlike prevalent methods that directly infer CNV profiles from the pattern of sequencing depth, our mfA platform denatures and separates the DNA molecules from a single cell into multiple fractions of a reaction mix before amplification. By examining the sequencing result of each fraction for a specific fragment and applying a segment-merge maximum likelihood algorithm to the calculation of copy number, we digitize the sequencing-depth-based CNV identification and thus provide a method that is less sensitive to the amplification bias. In this paper, we demonstrate a mfA platform through multiple displacement amplification (MDA) chemistry. When performing the mfA platform, the noise of MDA is reduced; therefore, the resolution of single-cell CNV identification can be improved to 100 kb. We can also determine the genomic region free of allelic drop-out with mfA platform, which is impossible for conventional single-cell amplification methods.

An integrated strategy for in vivo metabolite profiling using high-resolution mass spectrometry based data processing techniques

International Nuclear Information System (INIS)

Guo, Jian; Zhang, Minli; Elmore, Charles S.; Vishwanathan, Karthick

2013-01-01

Graphical abstract: -- Highlights: •Profiling the metabolites of model compounds in rats using high resolution mass spectrometry based data processing techniques. •Demonstrating an integrated strategy in vivo metabolite profiling using data mining tools. •Unusual metabolites generated via thiazole-ring opening were characterized based on processed LC–MS.data. -- Abstract: An ongoing challenge of drug metabolite profiling is to detect and identify unknown or low-level metabolites in complex biological matrices. Here we present a generic strategy for metabolite detection using multiple accurate-mass-based data processing tools via the analysis of rat samples of two model drug candidates, AZD6280 and AZ12488024. First, the function of isotopic pattern recognition was proved to be highly effective in the detection of metabolites derived from [ 14 C]-AZD6280 that possesses a distinct isotopic pattern. The metabolites revealed using this approach were in excellent qualitative correlation to those observed in radiochromatograms. Second, the effectiveness of accurate mass based untargeted data mining tools such as background subtraction, mass defect filtering, or a data mining package (MZmine) used for metabolomic analysis in detection of metabolites of [ 14 C]-AZ12488024 in rat urine, feces, bile and plasma samples was examined and a total of 33 metabolites of AZ12488024 were detected. Among them, at least 16 metabolites were only detected by the aid of the data mining packages and not via radiochromatograms. New metabolic pathways such as S-oxidation and thiomethylation reactions occurring on the thiazole ring were proposed based on the processed data. The results of these experiments also demonstrated that accurate mass-based mass defect filtering (MDF) and data mining techniques used in metabolomics are complementary and can be valuable tools for delineating low-level metabolites in complex matrices. Furthermore, the application of distinct multiple data

Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling

DEFF Research Database (Denmark)

Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute

2004-01-01

in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported......Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly...

Characterization of canine osteosarcoma by array comparative genomic hybridization and RT-qPCR: signatures of genomic imbalance in canine osteosarcoma parallel the human counterpart.

Science.gov (United States)

Angstadt, Andrea Y; Motsinger-Reif, Alison; Thomas, Rachael; Kisseberth, William C; Guillermo Couto, C; Duval, Dawn L; Nielsen, Dahlia M; Modiano, Jaime F; Breen, Matthew

2011-11-01

Osteosarcoma (OS) is the most commonly diagnosed malignant bone tumor in humans and dogs, characterized in both species by extremely complex karyotypes exhibiting high frequencies of genomic imbalance. Evaluation of genomic signatures in human OS using array comparative genomic hybridization (aCGH) has assisted in uncovering genetic mechanisms that result in disease phenotype. Previous low-resolution (10-20 Mb) aCGH analysis of canine OS identified a wide range of recurrent DNA copy number aberrations, indicating extensive genomic instability. In this study, we profiled 123 canine OS tumors by 1 Mb-resolution aCGH to generate a dataset for direct comparison with current data for human OS, concluding that several high frequency aberrations in canine and human OS are orthologous. To ensure complete coverage of gene annotation, we identified the human refseq genes that map to these orthologous aberrant dog regions and found several candidate genes warranting evaluation for OS involvement. Specifically, subsequenct FISH and qRT-PCR analysis of RUNX2, TUSC3, and PTEN indicated that expression levels correlated with genomic copy number status, showcasing RUNX2 as an OS associated gene and TUSC3 as a possible tumor suppressor candidate. Together these data demonstrate the ability of genomic comparative oncology to identify genetic abberations which may be important for OS progression. Large scale screening of genomic imbalance in canine OS further validates the use of the dog as a suitable model for human cancers, supporting the idea that dysregulation discovered in canine cancers will provide an avenue for complementary study in human counterparts. Copyright © 2011 Wiley-Liss, Inc.

The EUV dayglow at high spectral resolution

International Nuclear Information System (INIS)

Morrison, M.D.; Bowers, C.W.; Feldman, P.D.; Meier, R.R.

1990-01-01

Rocket observations of the dayglow spectrum of the terrestrial atmosphere between 840 angstrom and 1860 angstrom at 2 angstrom resolution were obtained with a sounding rocket payload flown on January 17, 1985. Additionally, spectra were also obtained using a 0.125-m focal length scanning Ebert-Fastie monochromator covering the wavelength interval of 1150-1550 angstrom at 7 angstrom resolution on this flight and on a sounding rocket flight on August 29, 1983, under similar viewing geometries and solar zenith angles. Three bands of the N 2 c' 4 system are seen clearly resolved in the dayglow. Analysis of high-resolution N 2 Lyman-Birge-Hopfield data shows no anomalous vibrational distribution as has been reported from other observations. The altitude profiles of the observed O and N 2 emissions demonstrate that the MSIS-83 model O and N 2 densities are appropriate for the conditions of both the 1983 and 1985 rocket flights. A reduction of a factor of 2 in the model O 2 density is required for both flights to reproduce the low-altitude atomic oxygen emission profiles. The volume excitation rates calculated using the Hinteregger et al. (1981) SC number-sign 21REFW solar reference spectrum and the photoelectron flux model of Strickland and Meier (1982) need to be scaled upward by a factor of 1.4 for both fights to match the observations

High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology

Science.gov (United States)

Mazars, Edith; Lesjean, Sarah; Banuls, Anne-Laure; Gilbert, Michèle; Vincent, Véronique; Gicquel, Brigitte; Tibayrenc, Michel; Locht, Camille; Supply, Philip

2001-01-01

The worldwide threat of tuberculosis to human health emphasizes the need to develop novel approaches to a global epidemiological surveillance. The current standard for Mycobacterium tuberculosis typing based on IS6110 restriction fragment length polymorphism (RFLP) suffers from the difficulty of comparing data between independent laboratories. Here, we propose a high-resolution typing method based on variable number tandem repeats (VNTRs) of genetic elements named mycobacterial interspersed repetitive units (MIRUs) in 12 human minisatellite-like regions of the M. tuberculosis genome. MIRU-VNTR profiles of 72 different M. tuberculosis isolates were established by PCR analysis of all 12 loci. From 2 to 8 MIRU-VNTR alleles were identified in the 12 regions in these strains, which corresponds to a potential of over 16 million different combinations, yielding a resolution power close to that of IS6110-RFLP. All epidemiologically related isolates tested were perfectly clustered by MIRU-VNTR typing, indicating that the stability of these MIRU-VNTRs is adequate to track outbreak episodes. The correlation between genetic relationships inferred from MIRU-VNTR and IS6110-RFLP typing was highly significant. Compared with IS6110-RFLP, high-resolution MIRU-VNTR typing has the considerable advantages of being fast, appropriate for all M. tuberculosis isolates, including strains that have a few IS6110 copies, and permitting easy and rapid comparison of results from independent laboratories. This typing method opens the way to the construction of digital global databases for molecular epidemiology studies of M. tuberculosis. PMID:11172048

Genome profiling of sterol synthesis shows convergent evolution in parasites and guides chemotherapeutic attack.

Science.gov (United States)

Fügi, Matthias A; Gunasekera, Kapila; Ochsenreiter, Torsten; Guan, Xueli; Wenk, Markus R; Mäser, Pascal

2014-05-01

Sterols are an essential class of lipids in eukaryotes, where they serve as structural components of membranes and play important roles as signaling molecules. Sterols are also of high pharmacological significance: cholesterol-lowering drugs are blockbusters in human health, and inhibitors of ergosterol biosynthesis are widely used as antifungals. Inhibitors of ergosterol synthesis are also being developed for Chagas's disease, caused by Trypanosoma cruzi. Here we develop an in silico pipeline to globally evaluate sterol metabolism and perform comparative genomics. We generate a library of hidden Markov model-based profiles for 42 sterol biosynthetic enzymes, which allows expressing the genomic makeup of a given species as a numerical vector. Hierarchical clustering of these vectors functionally groups eukaryote proteomes and reveals convergent evolution, in particular metabolic reduction in obligate endoparasites. We experimentally explore sterol metabolism by testing a set of sterol biosynthesis inhibitors against trypanosomatids, Plasmodium falciparum, Giardia, and mammalian cells, and by quantifying the expression levels of sterol biosynthetic genes during the different life stages of T. cruzi and Trypanosoma brucei. The phenotypic data correlate with genomic makeup for simvastatin, which showed activity against trypanosomatids. Other findings, such as the activity of terbinafine against Giardia, are not in agreement with the genotypic profile.

High Spectral Resolution Lidar Based on a Potassium Faraday Dispersive Filter for Daytime Temperature Measurement

Directory of Open Access Journals (Sweden)

Abo Makoto

2016-01-01

Full Text Available In this paper, a new high-spectral-resolution lidar technique is proposed for measuring the profiles of atmospheric temperature in daytime. Based on the theory of high resolution Rayleigh scattering, the feasibility and advantages of using potassium (K Faraday dispersive optical filters as blocking filters for measuring atmospheric temperature are demonstrated with a numerical simulation. It was found that temperature profiles could be measured within 1K error for the height of 9 km with a 500 m range resolution in 60 min by using laser pulses with 1mJ/pulse and 1 kHz, and a 50 cm diameter telescope. Furthermore, we are developing compact pulsed laser system for temperature lidar transmitter.

Flow Cytometric DNA index, G-band Karyotyping, and Comparative Genomic Hybridization in Detection of High Hyperdiploidy in Childhood Acute Lymphoblastic Leukemia

DEFF Research Database (Denmark)

Nygaard, Ulrikka; Larsen, Jacob; Kristensen, Tim D

2006-01-01

High hyperdiploid acute lymphoblastic leukemia in children is related to a good outcome. Because these patients may be stratified to a low-intensity treatment, we have investigated the sensitivity of flow cytometry (FCM), G-band karyotyping (GBK), and high-resolution comparative genomic hybridiza......High hyperdiploid acute lymphoblastic leukemia in children is related to a good outcome. Because these patients may be stratified to a low-intensity treatment, we have investigated the sensitivity of flow cytometry (FCM), G-band karyotyping (GBK), and high-resolution comparative genomic...

High-resolution analysis of the 5'-end transcriptome using a next generation DNA sequencer.

Directory of Open Access Journals (Sweden)

Shin-ichi Hashimoto

Full Text Available Massively parallel, tag-based sequencing systems, such as the SOLiD system, hold the promise of revolutionizing the study of whole genome gene expression due to the number of data points that can be generated in a simple and cost-effective manner. We describe the development of a 5'-end transcriptome workflow for the SOLiD system and demonstrate the advantages in sensitivity and dynamic range offered by this tag-based application over traditional approaches for the study of whole genome gene expression. 5'-end transcriptome analysis was used to study whole genome gene expression within a colon cancer cell line, HT-29, treated with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5Aza. More than 20 million 25-base 5'-end tags were obtained from untreated and 5Aza-treated cells and matched to sequences within the human genome. Seventy three percent of the mapped unique tags were associated with RefSeq cDNA sequences, corresponding to approximately 14,000 different protein-coding genes in this single cell type. The level of expression of these genes ranged from 0.02 to 4,704 transcripts per cell. The sensitivity of a single sequence run of the SOLiD platform was 100-1,000 fold greater than that observed from 5'end SAGE data generated from the analysis of 70,000 tags obtained by Sanger sequencing. The high-resolution 5'end gene expression profiling presented in this study will not only provide novel insight into the transcriptional machinery but should also serve as a basis for a better understanding of cell biology.

Dual High-Resolution α-Glucosidase and Radical Scavenging Profiling Combined with HPLC-HRMS-SPE-NMR for Identification of Minor and Major Constituents Directly from the Crude Extract of Pueraria lobata

DEFF Research Database (Denmark)

Liu, Bingrui; Kongstad, Kenneth Thermann; Qinglei, Sun

2015-01-01

The crude methanol extract of Pueraria lobata was investigated by dual high-resolution α-glucosidase inhibition and radical scavenging profiling combined with hyphenated HPLC-HRMS-SPE-NMR. Direct analysis of the crude extract without preceding purification was facilitated by combining chromatograms...... from two analytical-scale HPLC separations of 120 and 600 μg on-column, respectively. High-resolution α-glucosidase and radical scavenging profiles were obtained after microfractionation of the eluate in 96-well microplates. This allowed full bioactivity profiling of individual peaks in the HPLC...... chromatogram of the crude methanol extract. Subsequent HPLC-HRMS-SPE-NMR analysis allowed identification of 21 known compounds in addition to two new compounds, i.e., 3′-methoxydaidzein 8-C-[α-d-apiofuranosyl-(1→6)]-β-d-glucopyranoside and 6″-O-malonyl-3′-methoxydaidzin, as well as an unstable compound...

The Genomic and Transcriptomic Landscape of a HeLa Cell Line

Science.gov (United States)

Landry, Jonathan J. M.; Pyl, Paul Theodor; Rausch, Tobias; Zichner, Thomas; Tekkedil, Manu M.; Stütz, Adrian M.; Jauch, Anna; Aiyar, Raeka S.; Pau, Gregoire; Delhomme, Nicolas; Gagneur, Julien; Korbel, Jan O.; Huber, Wolfgang; Steinmetz, Lars M.

2013-01-01

HeLa is the most widely used model cell line for studying human cellular and molecular biology. To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome. Effective design and interpretation of molecular genetic studies performed using HeLa cells require accurate genomic information. Here we present a detailed genomic and transcriptomic characterization of a HeLa cell line. We performed DNA and RNA sequencing of a HeLa Kyoto cell line and analyzed its mutational portfolio and gene expression profile. Segmentation of the genome according to copy number revealed a remarkably high level of aneuploidy and numerous large structural variants at unprecedented resolution. Some of the extensive genomic rearrangements are indicative of catastrophic chromosome shattering, known as chromothripsis. Our analysis of the HeLa gene expression profile revealed that several pathways, including cell cycle and DNA repair, exhibit significantly different expression patterns from those in normal human tissues. Our results provide the first detailed account of genomic variants in the HeLa genome, yielding insight into their impact on gene expression and cellular function as well as their origins. This study underscores the importance of accounting for the strikingly aberrant characteristics of HeLa cells when designing and interpreting experiments, and has implications for the use of HeLa as a model of human biology. PMID:23550136

The need for high-quality whole-genome sequence databases in microbial forensics.

Science.gov (United States)

Sjödin, Andreas; Broman, Tina; Melefors, Öjar; Andersson, Gunnar; Rasmusson, Birgitta; Knutsson, Rickard; Forsman, Mats

2013-09-01

Microbial forensics is an important part of a strengthened capability to respond to biocrime and bioterrorism incidents to aid in the complex task of distinguishing between natural outbreaks and deliberate acts. The goal of a microbial forensic investigation is to identify and criminally prosecute those responsible for a biological attack, and it involves a detailed analysis of the weapon--that is, the pathogen. The recent development of next-generation sequencing (NGS) technologies has greatly increased the resolution that can be achieved in microbial forensic analyses. It is now possible to identify, quickly and in an unbiased manner, previously undetectable genome differences between closely related isolates. This development is particularly relevant for the most deadly bacterial diseases that are caused by bacterial lineages with extremely low levels of genetic diversity. Whole-genome analysis of pathogens is envisaged to be increasingly essential for this purpose. In a microbial forensic context, whole-genome sequence analysis is the ultimate method for strain comparisons as it is informative during identification, characterization, and attribution--all 3 major stages of the investigation--and at all levels of microbial strain identity resolution (ie, it resolves the full spectrum from family to isolate). Given these capabilities, one bottleneck in microbial forensics investigations is the availability of high-quality reference databases of bacterial whole-genome sequences. To be of high quality, databases need to be curated and accurate in terms of sequences, metadata, and genetic diversity coverage. The development of whole-genome sequence databases will be instrumental in successfully tracing pathogens in the future.

Classification of Ultra-High Resolution Orthophotos Combined with DSM Using a Dual Morphological Top Hat Profile

Directory of Open Access Journals (Sweden)

Qian Zhang

2015-12-01

Full Text Available New aerial sensors and platforms (e.g., unmanned aerial vehicles (UAVs are capable of providing ultra-high resolution remote sensing data (less than a 30-cm ground sampling distance (GSD. This type of data is an important source for interpreting sub-building level objects; however, it has not yet been explored. The large-scale differences of urban objects, the high spectral variability and the large perspective effect bring difficulties to the design of descriptive features. Therefore, features representing the spatial information of the objects are essential for dealing with the spectral ambiguity. In this paper, we proposed a dual morphology top-hat profile (DMTHP using both morphology reconstruction and erosion with different granularities. Due to the high dimensional feature space, we have proposed an adaptive scale selection procedure to reduce the feature dimension according to the training samples. The DMTHP is extracted from both images and Digital Surface Models (DSM to obtain complimentary information. The random forest classifier is used to classify the features hierarchically. Quantitative experimental results on aerial images with 9-cm and UAV images with 5-cm GSD are performed. Under our experiments, improvements of 10% and 2% in overall accuracy are obtained in comparison with the well-known differential morphological profile (DMP feature, and superior performance is observed over other tested features. Large format data with 20,000 × 20,000 pixels are used to perform a qualitative experiment using the proposed method, which shows its promising potential. The experiments also demonstrate that the DSM information has greatly enhanced the classification accuracy. In the best case in our experiment, it gives rise to a classification accuracy from 63.93% (spectral information only to 94.48% (the proposed method.

High resolution identity testing of inactivated poliovirus vaccines.

Science.gov (United States)

Mee, Edward T; Minor, Philip D; Martin, Javier

2015-07-09

Definitive identification of poliovirus strains in vaccines is essential for quality control, particularly where multiple wild-type and Sabin strains are produced in the same facility. Sequence-based identification provides the ultimate in identity testing and would offer several advantages over serological methods. We employed random RT-PCR and high throughput sequencing to recover full-length genome sequences from monovalent and trivalent poliovirus vaccine products at various stages of the manufacturing process. All expected strains were detected in previously characterised products and the method permitted identification of strains comprising as little as 0.1% of sequence reads. Highly similar Mahoney and Sabin 1 strains were readily discriminated on the basis of specific variant positions. Analysis of a product known to contain incorrect strains demonstrated that the method correctly identified the contaminants. Random RT-PCR and shotgun sequencing provided high resolution identification of vaccine components. In addition to the recovery of full-length genome sequences, the method could also be easily adapted to the characterisation of minor variant frequencies and distinction of closely related products on the basis of distinguishing consensus and low frequency polymorphisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genome-Wide Expression Profiling of Complex Regional Pain Syndrome

Science.gov (United States)

Jin, Eun-Heui; Zhang, Enji; Ko, Youngkwon; Sim, Woo Seog; Moon, Dong Eon; Yoon, Keon Jung; Hong, Jang Hee; Lee, Won Hyung

2013-01-01

Complex regional pain syndrome (CRPS) is a chronic, progressive, and devastating pain syndrome characterized by spontaneous pain, hyperalgesia, allodynia, altered skin temperature, and motor dysfunction. Although previous gene expression profiling studies have been conducted in animal pain models, there genome-wide expression profiling in the whole blood of CRPS patients has not been reported yet. Here, we successfully identified certain pain-related genes through genome-wide expression profiling in the blood from CRPS patients. We found that 80 genes were differentially expressed between 4 CRPS patients (2 CRPS I and 2 CRPS II) and 5 controls (cut-off value: 1.5-fold change and pCRPS patients and 18 controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We focused on the MMP9 gene that, by qRT-PCR, showed a statistically significant difference in expression in CRPS patients compared to controls with the highest relative fold change (4.0±1.23 times and p = 1.4×10−4). The up-regulation of MMP9 gene in the blood may be related to the pain progression in CRPS patients. Our findings, which offer a valuable contribution to the understanding of the differential gene expression in CRPS may help in the understanding of the pathophysiology of CRPS pain progression. PMID:24244504

High-throughput phenotyping and genomic selection: the frontiers of crop breeding converge.

Science.gov (United States)

Cabrera-Bosquet, Llorenç; Crossa, José; von Zitzewitz, Jarislav; Serret, María Dolors; Araus, José Luis

2012-05-01

Genomic selection (GS) and high-throughput phenotyping have recently been captivating the interest of the crop breeding community from both the public and private sectors world-wide. Both approaches promise to revolutionize the prediction of complex traits, including growth, yield and adaptation to stress. Whereas high-throughput phenotyping may help to improve understanding of crop physiology, most powerful techniques for high-throughput field phenotyping are empirical rather than analytical and comparable to genomic selection. Despite the fact that the two methodological approaches represent the extremes of what is understood as the breeding process (phenotype versus genome), they both consider the targeted traits (e.g. grain yield, growth, phenology, plant adaptation to stress) as a black box instead of dissecting them as a set of secondary traits (i.e. physiological) putatively related to the target trait. Both GS and high-throughput phenotyping have in common their empirical approach enabling breeders to use genome profile or phenotype without understanding the underlying biology. This short review discusses the main aspects of both approaches and focuses on the case of genomic selection of maize flowering traits and near-infrared spectroscopy (NIRS) and plant spectral reflectance as high-throughput field phenotyping methods for complex traits such as crop growth and yield. © 2012 Institute of Botany, Chinese Academy of Sciences.

High-density transcriptional initiation signals underline genomic islands in bacteria.

Directory of Open Access Journals (Sweden)

Qianli Huang

Full Text Available Genomic islands (GIs, frequently associated with the pathogenicity of bacteria and having a substantial influence on bacterial evolution, are groups of "alien" elements which probably undergo special temporal-spatial regulation in the host genome. Are there particular hallmark transcriptional signals for these "exotic" regions? We here explore the potential transcriptional signals that underline the GIs beyond the conventional views on basic sequence composition, such as codon usage and GC property bias. It showed that there is a significant enrichment of the transcription start positions (TSPs in the GI regions compared to the whole genome of Salmonella enterica and Escherichia coli. There was up to a four-fold increase for the 70% GIs, implying high-density TSPs profile can potentially differentiate the GI regions. Based on this feature, we developed a new sliding window method GIST, Genomic-island Identification by Signals of Transcription, to identify these regions. Subsequently, we compared the known GI-associated features of the GIs detected by GIST and by the existing method Islandviewer to those of the whole genome. Our method demonstrates high sensitivity in detecting GIs harboring genes with biased GI-like function, preferred subcellular localization, skewed GC property, shorter gene length and biased "non-optimal" codon usage. The special transcriptional signals discovered here may contribute to the coordinate expression regulation of foreign genes. Finally, by using GIST, we detected many interesting GIs in the 2011 German E. coli O104:H4 outbreak strain TY-2482, including the microcin H47 system and gene cluster ycgXEFZ-ymgABC that activates the production of biofilm matrix. The aforesaid findings highlight the power of GIST to predict GIs with distinct intrinsic features to the genome. The heterogeneity of cumulative TSPs profiles may not only be a better identity for "alien" regions, but also provide hints to the special

Profiles of Genomic Instability in High-Grade Serous Ovarian Cancer Predict Treatment Outcome

DEFF Research Database (Denmark)

Wang, Zhigang C.; Birkbak, Nicolai Juul; Culhane, Aedín C.

2012-01-01

Purpose: High-grade serous cancer (HGSC) is the most common cancer of the ovary and is characterized by chromosomal instability. Defects in homologous recombination repair (HRR) are associated with genomic instability in HGSC, and are exploited by therapy targeting DNA repair. Defective HRR cause...

Detecting DNA double-stranded breaks in mammalian genomes by linear amplification-mediated high-throughput genome-wide translocation sequencing.

Science.gov (United States)

Hu, Jiazhi; Meyers, Robin M; Dong, Junchao; Panchakshari, Rohit A; Alt, Frederick W; Frock, Richard L

2016-05-01

Unbiased, high-throughput assays for detecting and quantifying DNA double-stranded breaks (DSBs) across the genome in mammalian cells will facilitate basic studies of the mechanisms that generate and repair endogenous DSBs. They will also enable more applied studies, such as those to evaluate the on- and off-target activities of engineered nucleases. Here we describe a linear amplification-mediated high-throughput genome-wide sequencing (LAM-HTGTS) method for the detection of genome-wide 'prey' DSBs via their translocation in cultured mammalian cells to a fixed 'bait' DSB. Bait-prey junctions are cloned directly from isolated genomic DNA using LAM-PCR and unidirectionally ligated to bridge adapters; subsequent PCR steps amplify the single-stranded DNA junction library in preparation for Illumina Miseq paired-end sequencing. A custom bioinformatics pipeline identifies prey sequences that contribute to junctions and maps them across the genome. LAM-HTGTS differs from related approaches because it detects a wide range of broken end structures with nucleotide-level resolution. Familiarity with nucleic acid methods and next-generation sequencing analysis is necessary for library generation and data interpretation. LAM-HTGTS assays are sensitive, reproducible, relatively inexpensive, scalable and straightforward to implement with a turnaround time of <1 week.

Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.

Science.gov (United States)

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-05-01

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

NARCIS (Netherlands)

Wang, Kai; Yuen, Siu Tsan; Xu, Jiangchun; Lee, Siu Po; Yan, Helen H N; Shi, Stephanie T; Siu, Hoi Cheong; Deng, Shibing; Chu, Kent Man; Law, Simon; Chan, Kok Hoe; Chan, Annie S Y; Tsui, Wai Yin; Ho, Siu Lun; Chan, Anthony K W; Man, Jonathan L K; Foglizzo, Valentina; Ng, Man Kin; Chan, April S; Ching, Yick Pang; Cheng, Grace H W; Xie, Tao; Fernandez, Julio; Li, Vivian S W; Clevers, Hans; Rejto, Paul A; Mao, Mao; Leung, Suet Yi

Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and

Analysis of complete mitochondrial genomes from extinct and extant rhinoceroses reveals lack of phylogenetic resolution

Science.gov (United States)

Willerslev, Eske; Gilbert, M Thomas P; Binladen, Jonas; Ho, Simon YW; Campos, Paula F; Ratan, Aakrosh; Tomsho, Lynn P; da Fonseca, Rute R; Sher, Andrei; Kuznetsova, Tatanya V; Nowak-Kemp, Malgosia; Roth, Terri L; Miller, Webb; Schuster, Stephan C

2009-01-01

Background The scientific literature contains many examples where DNA sequence analyses have been used to provide definitive answers to phylogenetic problems that traditional (non-DNA based) approaches alone have failed to resolve. One notable example concerns the rhinoceroses, a group for which several contradictory phylogenies were proposed on the basis of morphology, then apparently resolved using mitochondrial DNA fragments. Results In this study we report the first complete mitochondrial genome sequences of the extinct ice-age woolly rhinoceros (Coelodonta antiquitatis), and the threatened Javan (Rhinoceros sondaicus), Sumatran (Dicerorhinus sumatrensis), and black (Diceros bicornis) rhinoceroses. In combination with the previously published mitochondrial genomes of the white (Ceratotherium simum) and Indian (Rhinoceros unicornis) rhinoceroses, this data set putatively enables reconstruction of the rhinoceros phylogeny. While the six species cluster into three strongly supported sister-pairings: (i) The black/white, (ii) the woolly/Sumatran, and (iii) the Javan/Indian, resolution of the higher-level relationships has no statistical support. The phylogenetic signal from individual genes is highly diffuse, with mixed topological support from different genes. Furthermore, the choice of outgroup (horse vs tapir) has considerable effect on reconstruction of the phylogeny. The lack of resolution is suggestive of a hard polytomy at the base of crown-group Rhinocerotidae, and this is supported by an investigation of the relative branch lengths. Conclusion Satisfactory resolution of the rhinoceros phylogeny may not be achievable without additional analyses of substantial amounts of nuclear DNA. This study provides a compelling demonstration that, in spite of substantial sequence length, there are significant limitations with single-locus phylogenetics. We expect further examples of this to appear as next-generation, large-scale sequencing of complete mitochondrial

Analysis of complete mitochondrial genomes from extinct and extant rhinoceroses reveals lack of phylogenetic resolution

Directory of Open Access Journals (Sweden)

Nowak-Kemp Malgosia

2009-05-01

Full Text Available Abstract Background The scientific literature contains many examples where DNA sequence analyses have been used to provide definitive answers to phylogenetic problems that traditional (non-DNA based approaches alone have failed to resolve. One notable example concerns the rhinoceroses, a group for which several contradictory phylogenies were proposed on the basis of morphology, then apparently resolved using mitochondrial DNA fragments. Results In this study we report the first complete mitochondrial genome sequences of the extinct ice-age woolly rhinoceros (Coelodonta antiquitatis, and the threatened Javan (Rhinoceros sondaicus, Sumatran (Dicerorhinus sumatrensis, and black (Diceros bicornis rhinoceroses. In combination with the previously published mitochondrial genomes of the white (Ceratotherium simum and Indian (Rhinoceros unicornis rhinoceroses, this data set putatively enables reconstruction of the rhinoceros phylogeny. While the six species cluster into three strongly supported sister-pairings: (i The black/white, (ii the woolly/Sumatran, and (iii the Javan/Indian, resolution of the higher-level relationships has no statistical support. The phylogenetic signal from individual genes is highly diffuse, with mixed topological support from different genes. Furthermore, the choice of outgroup (horse vs tapir has considerable effect on reconstruction of the phylogeny. The lack of resolution is suggestive of a hard polytomy at the base of crown-group Rhinocerotidae, and this is supported by an investigation of the relative branch lengths. Conclusion Satisfactory resolution of the rhinoceros phylogeny may not be achievable without additional analyses of substantial amounts of nuclear DNA. This study provides a compelling demonstration that, in spite of substantial sequence length, there are significant limitations with single-locus phylogenetics. We expect further examples of this to appear as next-generation, large-scale sequencing of complete

Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal

Science.gov (United States)

Gao, Jianjiong; Aksoy, Bülent Arman; Dogrusoz, Ugur; Dresdner, Gideon; Gross, Benjamin; Sumer, S. Onur; Sun, Yichao; Jacobsen, Anders; Sinha, Rileen; Larsson, Erik; Cerami, Ethan; Sander, Chris; Schultz, Nikolaus

2014-01-01

The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics. PMID:23550210

High resolution eddy current microscopy

Science.gov (United States)

Lantz, M. A.; Jarvis, S. P.; Tokumoto, H.

2001-01-01

We describe a sensitive scanning force microscope based technique for measuring local variations in resistivity by monitoring changes in the eddy current induced damping of a cantilever with a magnetic tip oscillating above a conducting sample. To achieve a high sensitivity, we used a cantilever with an FeNdBLa particle mounted on the tip. Resistivity measurements are demonstrated on a silicon test structure with a staircase doping profile. Regions with resistivities of 0.0013, 0.0041, and 0.022 Ω cm are clearly resolved with a lateral resolution of approximately 180 nm. For this range of resistivities, the eddy current induced damping is found to depend linearly on the sample resistivity.

Edge density profiles in high-performance JET plasmas

International Nuclear Information System (INIS)

Summers, D.D.R.; Viaccoz, B.; Vince, J.

1997-01-01

Detailed electron density profiles of the scrape-off layer in high-performance JET plasmas (plasma current, I p nbi ∝17 MW) have been measured by means of a lithium beam diagnostic system featuring high spatial resolution [Kadota (1978)[. Measurements were taken over a period of several seconds, allowing examination of the evolution of the edge profile at a location upstream from the divertor target. The data clearly show the effects of the H-mode transition - an increase in density near the plasma separatrix and a reduction in density scrape-off length. The profiles obtained under various plasma conditions are compared firstly with data from other diagnostics, located elsewhere in the vessel, and also with the predictions of an 'onion-skin' model (DIVIMP), which used, as initial parameters, data from an array of probes located in the divertor target. (orig.)

High resolution reservoir geological modelling using outcrop information

Energy Technology Data Exchange (ETDEWEB)

Zhang Changmin; Lin Kexiang; Liu Huaibo [Jianghan Petroleum Institute, Hubei (China)] [and others

1997-08-01

This is China`s first case study of high resolution reservoir geological modelling using outcrop information. The key of the modelling process is to build a prototype model and using the model as a geological knowledge bank. Outcrop information used in geological modelling including seven aspects: (1) Determining the reservoir framework pattern by sedimentary depositional system and facies analysis; (2) Horizontal correlation based on the lower and higher stand duration of the paleo-lake level; (3) Determining the model`s direction based on the paleocurrent statistics; (4) Estimating the sandbody communication by photomosaic and profiles; (6) Estimating reservoir properties distribution within sandbody by lithofacies analysis; and (7) Building the reservoir model in sandbody scale by architectural element analysis and 3-D sampling. A high resolution reservoir geological model of Youshashan oil field has been built by using this method.

D2B, a new high resolution neutron powder diffractometer at ILL Grenoble

International Nuclear Information System (INIS)

Hewat, A.W.

1987-01-01

Applications of high resolution neutron powder diffraction to materials science have grown rapidly in the past 10 years, with the development of Rietveld methods of profile refinement, and new high resolution diffractometers and multidetectors. Materials studied range from catalysts to zeolites, and from battery electrodes to prestressed superconducting wires. Although the techniques have now been adapted for X-ray and synchrotron radiation, neutron powder diffraction retains unique advantages. In this paper we describe the design and first test measurements on the latest high resolution powder diffractometer D2B at ILL Grenoble. A review of the applications is published in Chemica Scripta (1986). (author) 9 refs., 6 figs., 2 tabs

High-resolution X-ray television and high-resolution video recorders

International Nuclear Information System (INIS)

Haendle, J.; Horbaschek, H.; Alexandrescu, M.

1977-01-01

The improved transmission properties of the high-resolution X-ray television chain described here make it possible to transmit more information per television image. The resolution in the fluoroscopic image, which is visually determined, depends on the dose rate and the inertia of the television pick-up tube. This connection is discussed. In the last few years, video recorders have been increasingly used in X-ray diagnostics. The video recorder is a further quality-limiting element in X-ray television. The development of function patterns of high-resolution magnetic video recorders shows that this quality drop may be largely overcome. The influence of electrical band width and number of lines on the resolution in the X-ray television image stored is explained in more detail. (orig.) [de

High time resolution boundary layer description using combined remote sensing instruments

Directory of Open Access Journals (Sweden)

C. Gaffard

2008-09-01

Full Text Available Ground based remote sensing systems for future observation operations will allow continuous monitoring of the lower troposphere at temporal resolutions much better than every 30 min. Observations which may be considered spurious from an individual instrument can be validated or eliminated when considered in conjunction with measurements from other instruments observing at the same location. Thus, improved quality control of atmospheric profiles from microwave radiometers and wind profilers should be sought by considering the measurements from different systems together rather than individually. In future test bed deployments for future operational observing systems, this should be aided by observations from laser ceilometers and cloud radars. Observations of changes in atmospheric profiles at high temporal resolution in the lower troposphere are presented from a 12 channel microwave radiometer and 1290 MHz UHF wind profiler deployed in southern England during the CSIP field experiment in July/August 2005. The observations chosen were from days when thunderstorms occurred in southern England. Rapid changes near the surface in dry layers are considered, both when rain/hail may be falling from above and where the dry air is associated with cold pools behind organised thunderstorms. Also, short term variations in atmospheric profiles and vertical stability are presented on a day with occasional low cloud, when thunderstorms triggered 50 km down wind of the observing site Improved quality control of the individual remote sensing systems need to be implemented, examining the basic quality of the underlying observations as well as the final outputs, and so for instance eliminating ground clutter as far as possible from the basic Doppler spectra measurements of the wind profiler. In this study, this was performed manually. The potential of incorporating these types of instruments in future upper air observational networks leads to the challenge to

Whole-genome gene expression profiling of formalin-fixed, paraffin-embedded tissue samples.

Directory of Open Access Journals (Sweden)

Craig April

2009-12-01

Full Text Available We have developed a gene expression assay (Whole-Genome DASL, capable of generating whole-genome gene expression profiles from degraded samples such as formalin-fixed, paraffin-embedded (FFPE specimens.We demonstrated a similar level of sensitivity in gene detection between matched fresh-frozen (FF and FFPE samples, with the number and overlap of probes detected in the FFPE samples being approximately 88% and 95% of that in the corresponding FF samples, respectively; 74% of the differentially expressed probes overlapped between the FF and FFPE pairs. The WG-DASL assay is also able to detect 1.3-1.5 and 1.5-2 -fold changes in intact and FFPE samples, respectively. The dynamic range for the assay is approximately 3 logs. Comparing the WG-DASL assay with an in vitro transcription-based labeling method yielded fold-change correlations of R(2 approximately 0.83, while fold-change comparisons with quantitative RT-PCR assays yielded R(2 approximately 0.86 and R(2 approximately 0.55 for intact and FFPE samples, respectively. Additionally, the WG-DASL assay yielded high self-correlations (R(2>0.98 with low intact RNA inputs ranging from 1 ng to 100 ng; reproducible expression profiles were also obtained with 250 pg total RNA (R(2 approximately 0.92, with approximately 71% of the probes detected in 100 ng total RNA also detected at the 250 pg level. When FFPE samples were assayed, 1 ng total RNA yielded self-correlations of R(2 approximately 0.80, while still maintaining a correlation of R(2 approximately 0.75 with standard FFPE inputs (200 ng.Taken together, these results show that WG-DASL assay provides a reliable platform for genome-wide expression profiling in archived materials. It also possesses utility within clinical settings where only limited quantities of samples may be available (e.g. microdissected material or when minimally invasive procedures are performed (e.g. biopsied specimens.

Towards automatic metabolomic profiling of high-resolution one-dimensional proton NMR spectra

International Nuclear Information System (INIS)

Mercier, Pascal; Lewis, Michael J.; Chang, David; Baker, David; Wishart, David S.

2011-01-01

Nuclear magnetic resonance (NMR) and Mass Spectroscopy (MS) are the two most common spectroscopic analytical techniques employed in metabolomics. The large spectral datasets generated by NMR and MS are often analyzed using data reduction techniques like Principal Component Analysis (PCA). Although rapid, these methods are susceptible to solvent and matrix effects, high rates of false positives, lack of reproducibility and limited data transferability from one platform to the next. Given these limitations, a growing trend in both NMR and MS-based metabolomics is towards targeted profiling or “quantitative” metabolomics, wherein compounds are identified and quantified via spectral fitting prior to any statistical analysis. Despite the obvious advantages of this method, targeted profiling is hindered by the time required to perform manual or computer-assisted spectral fitting. In an effort to increase data analysis throughput for NMR-based metabolomics, we have developed an automatic method for identifying and quantifying metabolites in one-dimensional (1D) proton NMR spectra. This new algorithm is capable of using carefully constructed reference spectra and optimizing thousands of variables to reconstruct experimental NMR spectra of biofluids using rules and concepts derived from physical chemistry and NMR theory. The automated profiling program has been tested against spectra of synthetic mixtures as well as biological spectra of urine, serum and cerebral spinal fluid (CSF). Our results indicate that the algorithm can correctly identify compounds with high fidelity in each biofluid sample (except for urine). Furthermore, the metabolite concentrations exhibit a very high correlation with both simulated and manually-detected values.

Towards automatic metabolomic profiling of high-resolution one-dimensional proton NMR spectra

Energy Technology Data Exchange (ETDEWEB)

Mercier, Pascal; Lewis, Michael J.; Chang, David, E-mail: dchang@chenomx.com [Chenomx Inc (Canada); Baker, David [Pfizer Inc (United States); Wishart, David S. [University of Alberta, Department of Computing Science and Biological Sciences (Canada)

2011-04-15

Nuclear magnetic resonance (NMR) and Mass Spectroscopy (MS) are the two most common spectroscopic analytical techniques employed in metabolomics. The large spectral datasets generated by NMR and MS are often analyzed using data reduction techniques like Principal Component Analysis (PCA). Although rapid, these methods are susceptible to solvent and matrix effects, high rates of false positives, lack of reproducibility and limited data transferability from one platform to the next. Given these limitations, a growing trend in both NMR and MS-based metabolomics is towards targeted profiling or 'quantitative' metabolomics, wherein compounds are identified and quantified via spectral fitting prior to any statistical analysis. Despite the obvious advantages of this method, targeted profiling is hindered by the time required to perform manual or computer-assisted spectral fitting. In an effort to increase data analysis throughput for NMR-based metabolomics, we have developed an automatic method for identifying and quantifying metabolites in one-dimensional (1D) proton NMR spectra. This new algorithm is capable of using carefully constructed reference spectra and optimizing thousands of variables to reconstruct experimental NMR spectra of biofluids using rules and concepts derived from physical chemistry and NMR theory. The automated profiling program has been tested against spectra of synthetic mixtures as well as biological spectra of urine, serum and cerebral spinal fluid (CSF). Our results indicate that the algorithm can correctly identify compounds with high fidelity in each biofluid sample (except for urine). Furthermore, the metabolite concentrations exhibit a very high correlation with both simulated and manually-detected values.

Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles

Science.gov (United States)

Loudin, Michael G.; Wang, Jinhua; Leung, Hon-Chiu Eastwood; Gurusiddappa, Sivashankarappa; Meyer, Julia; Condos, Gregory; Morrison, Debra; Tsimelzon, Anna; Devidas, Meenakshi; Heerema, Nyla A.; Carroll, Andrew J.; Plon, Sharon E.; Hunger, Stephen P.; Basso, Giuseppe; Pession, Andrea; Bhojwani, Deepa; Carroll, William L.; Rabin, Karen R.

2014-01-01

Patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have distinct clinical and biological features. Whereas most DS-ALL cases lack the sentinel cytogenetic lesions that guide risk assignment in childhood ALL, JAK2 mutations and CRLF2 overexpression are highly enriched. To further characterize the unique biology of DS-ALL, we performed genome-wide profiling of 58 DS-ALL and 68 non-Down syndrome (NDS) ALL cases by DNA copy number, loss of heterozygosity, gene expression, and methylation analyses. We report a novel deletion within the 6p22 histone gene cluster as significantly more frequent in DS-ALL, occurring in 11 DS (22%) and only two NDS cases (3.1%) (Fisher’s exact p = 0.002). Homozygous deletions yielded significantly lower histone expression levels, and were associated with higher methylation levels, distinct spatial localization of methylated promoters, and enrichment of highly methylated genes for specific pathways and transcription factor binding motifs. Gene expression profiling demonstrated heterogeneity of DS-ALL cases overall, with supervised analysis defining a 45-transcript signature associated with CRLF2 overexpression. Further characterization of pathways associated with histone deletions may identify opportunities for novel targeted interventions. PMID:21647151

Metabolite profiling of carbamazepine and ibuprofen in Solea senegalensis bile using high-resolution mass spectrometry.

Science.gov (United States)

Aceña, Jaume; Pérez, Sandra; Eichhorn, Peter; Solé, Montserrat; Barceló, Damià

2017-09-01

The widespread occurrence of pharmaceuticals in the aquatic environment has raised concerns about potential adverse effects on exposed wildlife. Very little is currently known on exposure levels and clearance mechanisms of drugs in marine fish. Within this context, our research was focused on the identification of main metabolic reactions, generated metabolites, and caused effects after exposure of fish to carbamazepine (CBZ) and ibuprofen (IBU). To this end, juveniles of Solea senegalensis acclimated to two temperature regimes of 15 and 20 °C for 60 days received a single intraperitoneal dose of these drugs. A control group was administered the vehicle (sunflower oil). Bile samples were analyzed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry on a Q Exactive (Orbitrap) system, allowing to propose plausible identities for 11 metabolites of CBZ and 13 metabolites of IBU in fish bile. In case of CBZ metabolites originated from aromatic and benzylic hydroxylation, epoxidation, and ensuing O-glucuronidation, O-methylation of a catechol-like metabolite was also postulated. Ibuprofen, in turn, formed multiple hydroxyl metabolites, O-glucuronides, and (hydroxyl)-acyl glucuronides, in addition to several taurine conjugates. Enzymatic responses after drug exposures revealed a water temperature-dependent induction of microsomal carboxylesterases. The metabolite profiling in fish bile provides an important tool for pharmaceutical exposure assessment. Graphical abstract Studies of metabolism of carbamazepine and ibuprofen in fish.

Microsatellite instability in pediatric high grade glioma is associated with genomic profile and differential target gene inactivation.

Directory of Open Access Journals (Sweden)

Marta Viana-Pereira

Full Text Available High grade gliomas (HGG are one of the leading causes of cancer-related deaths in children, and there is increasing evidence that pediatric HGG may harbor distinct molecular characteristics compared to adult tumors. We have sought to clarify the role of microsatellite instability (MSI in pediatric versus adult HGG. MSI status was determined in 144 patients (71 pediatric and 73 adults using a well established panel of five quasimonomorphic mononucleotide repeat markers. Expression of MLH1, MSH2, MSH6 and PMS2 was determined by immunohistochemistry, MLH1 was assessed for mutations by direct sequencing and promoter methylation using MS-PCR. DNA copy number profiles were derived using array CGH, and mutations in eighteen MSI target genes studied by multiplex PCR and genotyping. MSI was found in 14/71 (19.7% pediatric cases, significantly more than observed in adults (5/73, 6.8%; p = 0.02, Chi-square test. MLH1 expression was downregulated in 10/13 cases, however no mutations or promoter methylation were found. MSH6 was absent in one pediatric MSI-High tumor, consistent with an inherited mismatch repair deficiency associated with germline MSH6 mutation. MSI was classed as Type A, and associated with a remarkably stable genomic profile. Of the eighteen classic MSI target genes, we identified mutations only in MSH6 and DNAPKcs and described a polymorphism in MRE11 without apparent functional consequences in DNA double strand break detection and repair. This study thus provides evidence for a potential novel molecular pathway in a proportion of gliomas associated with the presence of MSI.

Edible seaweed as future functional food: Identification of α-glucosidase inhibitors by combined use of high-resolution α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR

DEFF Research Database (Denmark)

Liu, Bingrui; Kongstad, Kenneth Thermann; Wiese, Stefanie

2016-01-01

-glucosidase inhibition profiling combined with high-performance liquid chromatography–high-resolution mass spectrometry–solid-phase extraction–nuclear magnetic resonance spectroscopy (HR-bioassay/HPLC–HRMS–SPE–NMR). The results showed Ascophyllum nodosum and Fucus vesicolosus to be rich in antioxidants, equaling...... as fatty acids – with oleic acid, linoleic acid and eicosapentaenoic acid being the most potent with IC50 values of 0.069, 0.075 and 0.10 mM, respectively, and showing a mixed-type inhibition mode....

TERRA REF: Advancing phenomics with high resolution, open access sensor and genomics data

Science.gov (United States)

LeBauer, D.; Kooper, R.; Burnette, M.; Willis, C.

2017-12-01

Automated plant measurement has the potential to improve understanding of genetic and environmental controls on plant traits (phenotypes). The application of sensors and software in the automation of high throughput phenotyping reflects a fundamental shift from labor intensive hand measurements to drone, tractor, and robot mounted sensing platforms. These tools are expected to speed the rate of crop improvement by enabling plant breeders to more accurately select plants with improved yields, resource use efficiency, and stress tolerance. However, there are many challenges facing high throughput phenomics: sensors and platforms are expensive, currently there are few standard methods of data collection and storage, and the analysis of large data sets requires high performance computers and automated, reproducible computing pipelines. To overcome these obstacles and advance the science of high throughput phenomics, the TERRA Phenotyping Reference Platform (TERRA-REF) team is developing an open-access database of high resolution sensor data. TERRA REF is an integrated field and greenhouse phenotyping system that includes: a reference field scanner with fifteen sensors that can generate terrabytes of data each day at mm resolution; UAV, tractor, and fixed field sensing platforms; and an automated controlled-environment scanner. These platforms will enable investigation of diverse sensing modalities, and the investigation of traits under controlled and field environments. It is the goal of TERRA REF to lower the barrier to entry for academic and industry researchers by providing high-resolution data, open source software, and online computing resources. Our project is unique in that all data will be made fully public in November 2018, and is already available to early adopters through the beta-user program. We will describe the datasets and how to use them as well as the databases and computing pipeline and how these can be reused and remixed in other phenomics pipelines

High-resolution typing of Chlamydia trachomatis: epidemiological and clinical uses.

Science.gov (United States)

de Vries, Henry J C; Schim van der Loeff, Maarten F; Bruisten, Sylvia M

2015-02-01

A state-of-the-art overview of molecular Chlamydia trachomatis typing methods that are used for routine diagnostics and scientific studies. Molecular epidemiology uses high-resolution typing techniques such as multilocus sequence typing, multilocus variable number of tandem repeats analysis, and whole-genome sequencing to identify strains based on their DNA sequence. These data can be used for cluster, network and phylogenetic analyses, and are used to unveil transmission networks, risk groups, and evolutionary pathways. High-resolution typing of C. trachomatis strains is applied to monitor treatment efficacy and re-infections, and to study the recent emergence of lymphogranuloma venereum (LGV) amongst men who have sex with men in high-income countries. Chlamydia strain typing has clinical relevance in disease management, as LGV needs longer treatment than non-LGV C. trachomatis. It has also led to the discovery of a new variant Chlamydia strain in Sweden, which was not detected by some commercial C. trachomatis diagnostic platforms. After a brief history and comparison of the various Chlamydia typing methods, the applications of the current techniques are described and future endeavors to extend scientific understanding are formulated. High-resolution typing will likely help to further unravel the pathophysiological mechanisms behind the wide clinical spectrum of chlamydial disease.

The expression profile of phosphatidylinositol in high spatial resolution imaging mass spectrometry as a potential biomarker for prostate cancer.

Directory of Open Access Journals (Sweden)

Takayuki Goto

Full Text Available High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS is an emerging application for the comprehensive and detailed analysis of the spatial distribution of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500-1000 was performed on optimal cutting temperature (OCT compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS showed that these molecules included 14 phosphatidylinositols (PIs, 3 phosphatidylethanolamines (PEs and 3 phosphatidic acids (PAs. Among the PIs, the expression of PI(18:0/18:1, PI(18:0/20:3 and PI(18:0/20:2 were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA. The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.

Increasing phylogenetic resolution at low taxonomic levels using massively parallel sequencing of chloroplast genomes

Directory of Open Access Journals (Sweden)

Cronn Richard

2009-12-01

Full Text Available Abstract Background Molecular evolutionary studies share the common goal of elucidating historical relationships, and the common challenge of adequately sampling taxa and characters. Particularly at low taxonomic levels, recent divergence, rapid radiations, and conservative genome evolution yield limited sequence variation, and dense taxon sampling is often desirable. Recent advances in massively parallel sequencing make it possible to rapidly obtain large amounts of sequence data, and multiplexing makes extensive sampling of megabase sequences feasible. Is it possible to efficiently apply massively parallel sequencing to increase phylogenetic resolution at low taxonomic levels? Results We reconstruct the infrageneric phylogeny of Pinus from 37 nearly-complete chloroplast genomes (average 109 kilobases each of an approximately 120 kilobase genome generated using multiplexed massively parallel sequencing. 30/33 ingroup nodes resolved with ≥ 95% bootstrap support; this is a substantial improvement relative to prior studies, and shows massively parallel sequencing-based strategies can produce sufficient high quality sequence to reach support levels originally proposed for the phylogenetic bootstrap. Resampling simulations show that at least the entire plastome is necessary to fully resolve Pinus, particularly in rapidly radiating clades. Meta-analysis of 99 published infrageneric phylogenies shows that whole plastome analysis should provide similar gains across a range of plant genera. A disproportionate amount of phylogenetic information resides in two loci (ycf1, ycf2, highlighting their unusual evolutionary properties. Conclusion Plastome sequencing is now an efficient option for increasing phylogenetic resolution at lower taxonomic levels in plant phylogenetic and population genetic analyses. With continuing improvements in sequencing capacity, the strategies herein should revolutionize efforts requiring dense taxon and character sampling

Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.

Directory of Open Access Journals (Sweden)

Shinya Akatsuka

Full Text Available Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.

A Perfect Match Genomic Landscape Provides a Unified Framework for the Precise Detection of Variation in Natural and Synthetic Haploid Genomes.

Science.gov (United States)

Palacios-Flores, Kim; García-Sotelo, Jair; Castillo, Alejandra; Uribe, Carina; Aguilar, Luis; Morales, Lucía; Gómez-Romero, Laura; Reyes, José; Garciarubio, Alejandro; Boege, Margareta; Dávila, Guillermo

2018-04-01

We present a conceptually simple, sensitive, precise, and essentially nonstatistical solution for the analysis of genome variation in haploid organisms. The generation of a Perfect Match Genomic Landscape (PMGL), which computes intergenome identity with single nucleotide resolution, reveals signatures of variation wherever a query genome differs from a reference genome. Such signatures encode the precise location of different types of variants, including single nucleotide variants, deletions, insertions, and amplifications, effectively introducing the concept of a general signature of variation. The precise nature of variants is then resolved through the generation of targeted alignments between specific sets of sequence reads and known regions of the reference genome. Thus, the perfect match logic decouples the identification of the location of variants from the characterization of their nature, providing a unified framework for the detection of genome variation. We assessed the performance of the PMGL strategy via simulation experiments. We determined the variation profiles of natural genomes and of a synthetic chromosome, both in the context of haploid yeast strains. Our approach uncovered variants that have previously escaped detection. Moreover, our strategy is ideally suited for further refining high-quality reference genomes. The source codes for the automated PMGL pipeline have been deposited in a public repository. Copyright © 2018 by the Genetics Society of America.

Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.

Science.gov (United States)

Ross, Jeffrey S; Wang, Kai; Khaira, Depinder; Ali, Siraj M; Fisher, Huge A G; Mian, Badar; Nazeer, Tipu; Elvin, Julia A; Palma, Norma; Yelensky, Roman; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Subbiah, Vivek; Pal, Sumanta K

2016-03-01

In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; PCancer 2016;122:702-711. © 2015 American Cancer Society. © 2015 American Cancer Society.

Mission profile resolution effects on lifetime estimation of doubly-fed induction generator power converter

DEFF Research Database (Denmark)

Zhang, Guanguan; Zhou, Dao; Blaabjerg, Frede

2017-01-01

, and the corresponding thermal modeling of power semiconductors are discussed. Accordingly, effects of different mission profiles on the consumed lifetime of the power converter are evaluated. In the above three thermal cycles, the IGBT of the grid-side converter and the diode of the rotor-side converter are more...... fragile, and the total consumed lifetimes are higher. Moreover, the short-term thermal cycles with milliseconds resolution induce the unbalance of the lifetime between the diode and IGBT of the grid-side converter, while thermal cycles with hour, second, and millisecond resolution consumes the similar......In the wind energy generation system, mission profiles are complicated, which range from seconds to years. In order to estimate the consumed lifetime of the power converter, wind speed profiles with the time resolution of 1 hour, 1 second and 0.5 millisecond are studied in this paper...

Genetic profiles of gastroesophageal cancer: combined analysis using expression array and tiling array--comparative genomic hybridization

DEFF Research Database (Denmark)

Isinger-Ekstrand, Anna; Johansson, Jan; Ohlsson, Mattias

2010-01-01

We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high......15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction, with upregulation in one quarter of the tumors. Gains....../losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can...

A high-frequency sonar for profiling small-scale subaqueous bedforms

Science.gov (United States)

Dingler, J.R.; Boylls, J.C.; Lowe, R.L.

1977-01-01

A high-resolution ultrasonic profiler has been developed which permits both laboratory and field studies of small-scale subaqueous bedforms. The device uses a 2.5-cm diameter piezoelectric ceramic crystal pulsed at a frequency of 4.5 MHz to obtain vertical accuracy and resolution of at least 1 mm. Compared to other small-scale profiling methods, this ultrasonic technique profiles the bottom more accurately and more rapidly without disturbing the bedforms. These characteristics are vital in wave-dominated nearshore zones where oscillatory flow and low visibility for the most part have stymied detailed bedform studies. In the laboratory the transducer is mounted directly to an instrument carriage. For field work the transducer housing is mounted in a 2 m long aluminum frame which is situated and operated by scuba divers. Observations using the device include ripple geometry and migration, the suspension height of sand during sheet flow, and long-term erosion/deposition at a point. ?? 1977.

Development of a High Resolution X-Ray Imaging Crystal Spectrometer for Measurement of Ion-Temperature and Rotation-Velocity Profiles in Fusion Energy Research Plasmas

International Nuclear Information System (INIS)

Hill, K.W.; Bitter, M.L.; Broennimann, Ch.; Eikenberry, E.F.; Ince-Cushman, A.; Lee, S.G.; Rice, J.E.; Scott, S.; Barnsley, R.

2008-01-01

A new imaging high resolution x-ray crystal spectrometer (XCS) has been developed to measure continuous profiles of ion temperature and rotation velocity in fusion plasmas. Following proof-of-principle tests on the Alcator C-Mod tokamak and the NSTX spherical tokamak, and successful testing of a new silicon, pixilated detector with 1MHz count rate capability per pixel, an imaging XCS is being designed to measure full profiles of T i and ν φ on C-Mod. The imaging XCS design has also been adopted for ITER. Ion-temperature uncertainty and minimum measurable rotation velocity are calculated for the C-Mod spectrometer. The affects of x-ray and nuclear-radiation background on the measurement uncertainties are calculated to predict performance on ITER

High-resolution phenotypic profiling of natural products-induced effects on the single-cell level

KAUST Repository

Kremb, Stephan Georg; Voolstra, Christian R.

2017-01-01

Natural products (NPs) are highly evolved molecules making them a valuable resource for new therapeutics. Here we demonstrate the usefulness of broad-spectrum phenotypic profiling of NP-induced perturbations on single cells with imaging-based High

High-resolution α-glucosidase inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of anti-diabetic compounds in Eremanthus crotonoides (Asteraceae)

DEFF Research Database (Denmark)

Lana e Silva, Eder; Felipe Revoredo Lobo, Jonathas; Vinther, Joachim Møllesøe

2016-01-01

with an inhibitory concentration (IC50) of 34.5 μg/mL towards α-glucosidase was investigated by high-resolution α-glucosidase inhibition profiling combined with HPLC-HRMS-SPE-NMR. This led to identification of six α-glucosidase inhibitors, namely quercetin (16), trans-tiliroside (17), luteolin (19), quercetin-3.......93 and 5.20 μM, respectively. This is the first report of the α-glucosidase inhibitory activity of compounds 20, 26, and 29, and the findings support the important role of Eremanthus species as novel sources of new drugs and/or herbal remedies for treatment of type 2 diabetes....

A high resolution, single bunch, beam profile monitor

International Nuclear Information System (INIS)

Norem, J.

1992-01-01

We developed a beam monitoring system which could be used to measure beam profile, size and stability at the final forms of a beamline or collider. The system uses nonimaging bremsstrahlung optics. The immediate use for this system would be examining the final focus spot at the SLAC/FFTR

High-speed and high-ratio referential genome compression.

Science.gov (United States)

Liu, Yuansheng; Peng, Hui; Wong, Limsoon; Li, Jinyan

2017-11-01

The rapidly increasing number of genomes generated by high-throughput sequencing platforms and assembly algorithms is accompanied by problems in data storage, compression and communication. Traditional compression algorithms are unable to meet the demand of high compression ratio due to the intrinsic challenging features of DNA sequences such as small alphabet size, frequent repeats and palindromes. Reference-based lossless compression, by which only the differences between two similar genomes are stored, is a promising approach with high compression ratio. We present a high-performance referential genome compression algorithm named HiRGC. It is based on a 2-bit encoding scheme and an advanced greedy-matching search on a hash table. We compare the performance of HiRGC with four state-of-the-art compression methods on a benchmark dataset of eight human genomes. HiRGC takes compress about 21 gigabytes of each set of the seven target genomes into 96-260 megabytes, achieving compression ratios of 217 to 82 times. This performance is at least 1.9 times better than the best competing algorithm on its best case. Our compression speed is also at least 2.9 times faster. HiRGC is stable and robust to deal with different reference genomes. In contrast, the competing methods' performance varies widely on different reference genomes. More experiments on 100 human genomes from the 1000 Genome Project and on genomes of several other species again demonstrate that HiRGC's performance is consistently excellent. The C ++ and Java source codes of our algorithm are freely available for academic and non-commercial use. They can be downloaded from https://github.com/yuansliu/HiRGC. jinyan.li@uts.edu.au. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Insights into structural variations and genome rearrangements in prokaryotic genomes.

Science.gov (United States)

Periwal, Vinita; Scaria, Vinod

2015-01-01

Structural variations (SVs) are genomic rearrangements that affect fairly large fragments of DNA. Most of the SVs such as inversions, deletions and translocations have been largely studied in context of genetic diseases in eukaryotes. However, recent studies demonstrate that genome rearrangements can also have profound impact on prokaryotic genomes, leading to altered cell phenotype. In contrast to single-nucleotide variations, SVs provide a much deeper insight into organization of bacterial genomes at a much better resolution. SVs can confer change in gene copy number, creation of new genes, altered gene expression and many other functional consequences. High-throughput technologies have now made it possible to explore SVs at a much refined resolution in bacterial genomes. Through this review, we aim to highlight the importance of the less explored field of SVs in prokaryotic genomes and their impact. We also discuss its potential applicability in the emerging fields of synthetic biology and genome engineering where targeted SVs could serve to create sophisticated and accurate genome editing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

High Resolution Temperature Measurement of Liquid Stainless Steel Using Hyperspectral Imaging

Directory of Open Access Journals (Sweden)

Wim Devesse

2017-01-01

Full Text Available A contactless temperature measurement system is presented based on a hyperspectral line camera that captures the spectra in the visible and near infrared (VNIR region of a large set of closely spaced points. The measured spectra are used in a nonlinear least squares optimization routine to calculate a one-dimensional temperature profile with high spatial resolution. Measurements of a liquid melt pool of AISI 316L stainless steel show that the system is able to determine the absolute temperatures with an accuracy of 10%. The measurements are made with a spatial resolution of 12 µm/pixel, justifying its use in applications where high temperature measurements with high spatial detail are desired, such as in the laser material processing and additive manufacturing fields.

ANL high resolution injector

International Nuclear Information System (INIS)

Minehara, E.; Kutschera, W.; Hartog, P.D.; Billquist, P.

1985-01-01

The ANL (Argonne National Laboratory) high-resolution injector has been installed to obtain higher mass resolution and higher preacceleration, and to utilize effectively the full mass range of ATLAS (Argonne Tandem Linac Accelerator System). Preliminary results of the first beam test are reported briefly. The design and performance, in particular a high-mass-resolution magnet with aberration compensation, are discussed. 7 refs., 5 figs., 2 tabs

High-resolution array CGH profiling identifies Na/K transporting ATPase interacting 2 (NKAIN2) as a predisposing candidate gene in neuroblastoma.

Science.gov (United States)

Romania, Paolo; Castellano, Aurora; Surace, Cecilia; Citti, Arianna; De Ioris, Maria Antonietta; Sirleto, Pietro; De Mariano, Marilena; Longo, Luca; Boldrini, Renata; Angioni, Adriano; Locatelli, Franco; Fruci, Doriana

2013-01-01

Neuroblastoma (NB), the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH) analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2) locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation.

High-resolution array CGH profiling identifies Na/K transporting ATPase interacting 2 (NKAIN2 as a predisposing candidate gene in neuroblastoma.

Directory of Open Access Journals (Sweden)

Paolo Romania

Full Text Available Neuroblastoma (NB, the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2 locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation.

Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia

KAUST Repository

Mojib, Nazia; Amad, Maan H.; Thimma, Manjula; Aldanondo, Naroa; Kumaran, Mande; Irigoien, Xabier

2014-01-01

The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid–protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin–protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton.

Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia

KAUST Repository

Mojib, Nazia

2014-06-01

The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid–protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin–protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton.

Investigation of the spatial structure and interactions of the genome at sub-kilobase-pair resolution using T2C.

Science.gov (United States)

Kolovos, Petros; Brouwer, Rutger W W; Kockx, Christel E M; Lesnussa, Michael; Kepper, Nick; Zuin, Jessica; Imam, A M Ali; van de Werken, Harmen J G; Wendt, Kerstin S; Knoch, Tobias A; van IJcken, Wilfred F J; Grosveld, Frank

2018-03-01

Chromosome conformation capture (3C) and its derivatives (e.g., 4C, 5C and Hi-C) are used to analyze the 3D organization of genomes. We recently developed targeted chromatin capture (T2C), an inexpensive method for studying the 3D organization of genomes, interactomes and structural changes associated with gene regulation, the cell cycle, and cell survival and development. Here, we present the protocol for T2C based on capture, describing all experimental steps and bio-informatic tools in full detail. T2C offers high resolution, a large dynamic interaction frequency range and a high signal-to-noise ratio. Its resolution is determined by the resulting fragment size of the chosen restriction enzyme, which can lead to sub-kilobase-pair resolution. T2C's high coverage allows the identification of the interactome of each individual DNA fragment, which makes binning of reads (often used in other methods) basically unnecessary. Notably, T2C requires low sequencing efforts. T2C also allows multiplexing of samples for the direct comparison of multiple samples. It can be used to study topologically associating domains (TADs), determining their position, shape, boundaries, and intra- and inter-domain interactions, as well as the composition of aggregated loops, interactions between nucleosomes, individual transcription factor binding sites, and promoters and enhancers. T2C can be performed by any investigator with basic skills in molecular biology techniques in ∼7-8 d. Data analysis requires basic expertise in bioinformatics and in Linux and Python environments.

High-resolution seismic reflection study, Vacherie Dome

International Nuclear Information System (INIS)

1984-06-01

A high-resolution seismic reflection study, consisting of recording, processing, and interpreting four seismic reflection lines, was made at Vacherie Dome, Louisiana. The presumed shape of the dome, as pictured in the geologic area characterization report by Law Engineering Testing Company in 1982, was based largely on interpretation of gravity data, constrained by a few wells and exploration-type seismic profiles. The purpose of the study was to obtain refined profiles of the dome above -914 m (-3000 ft) elevation. Additional study had been recommended by Louisiana State University in 1967 and the Office of Nuclear Waste Isolation in 1981 because the interpreted size of Vacherie Dome was based on limited seismic and gravity data. Forty-eight traces of seismic data were recorded each time shots were made to generate energy. Twelve-fold, common-depth-point data were obtained using geophone stations spaced at 15-m (50-ft) intervals with shots at 30-m (100-ft) intervals. The time-sampling interval used was 1 ms. Processing intended to enhance resolution included iterative static corrections, deconvolution before stacking, and both time- and depth-migration. The locations of the steep dome sides were inferred primarily from terminations of strong reflections (migrated) from strata near the top of the upper and lower Cretaceous sections. This interpretation agrees closely with the presumed shape from the top of the dome to about -610 m (-2000 ft) elevation, but below this on three of the profiles, this interpretation indicates a steeper salt face than the presumed shape. The area reduction at -914 m (-3000 ft) elevation is estimated to be on the order of 20 percent. 10 references, 11 figures, 4 tables

High-Resolution Amplified Fragment Length Polymorphism Typing of Lactococcus lactis Strains Enables Identification of Genetic Markers for Subspecies-Related Phenotypes▿

Science.gov (United States)

Kütahya, Oylum Erkus; Starrenburg, Marjo J. C.; Rademaker, Jan L. W.; Klaassen, Corné H. W.; van Hylckama Vlieg, Johan E. T.; Smid, Eddy J.; Kleerebezem, Michiel

2011-01-01

A high-resolution amplified fragment length polymorphism (AFLP) methodology was developed to achieve the delineation of closely related Lactococcus lactis strains. The differentiation depth of 24 enzyme-primer-nucleotide combinations was experimentally evaluated to maximize the number of polymorphisms. The resolution depth was confirmed by performing diversity analysis on 82 L. lactis strains, including both closely and distantly related strains with dairy and nondairy origins. Strains clustered into two main genomic lineages of L. lactis subsp. lactis and L. lactis subsp. cremoris type-strain-like genotypes and a third novel genomic lineage rooted from the L. lactis subsp. lactis genomic lineage. Cluster differentiation was highly correlated with small-subunit rRNA homology and multilocus sequence analysis (MLSA) studies. Additionally, the selected enzyme-primer combination generated L. lactis subsp. cremoris phenotype-specific fragments irrespective of the genotype. These phenotype-specific markers allowed the differentiation of L. lactis subsp. lactis phenotype from L. lactis subsp. cremoris phenotype strains within the same L. lactis subsp. cremoris type-strain-like genomic lineage, illustrating the potential of AFLP for the generation of phenotype-linked genetic markers. PMID:21666014

Hapsembler: An Assembler for Highly Polymorphic Genomes

Science.gov (United States)

Donmez, Nilgun; Brudno, Michael

As whole genome sequencing has become a routine biological experiment, algorithms for assembly of whole genome shotgun data has become a topic of extensive research, with a plethora of off-the-shelf methods that can reconstruct the genomes of many organisms. Simultaneously, several recently sequenced genomes exhibit very high polymorphism rates. For these organisms genome assembly remains a challenge as most assemblers are unable to handle highly divergent haplotypes in a single individual. In this paper we describe Hapsembler, an assembler for highly polymorphic genomes, which makes use of paired reads. Our experiments show that Hapsembler produces accurate and contiguous assemblies of highly polymorphic genomes, while performing on par with the leading tools on haploid genomes. Hapsembler is available for download at http://compbio.cs.toronto.edu/hapsembler.

Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic field using a single-sided NMR scanner applied to articular cartilage

Science.gov (United States)

Rössler, Erik; Mattea, Carlos; Stapf, Siegfried

2015-02-01

Low field Nuclear Magnetic Resonance increases the contrast of the longitudinal relaxation rate in many biological tissues; one prominent example is hyaline articular cartilage. In order to take advantage of this increased contrast and to profile the depth-dependent variations, high resolution parameter measurements are carried out which can be of critical importance in an early diagnosis of cartilage diseases such as osteoarthritis. However, the maximum achievable spatial resolution of parameter profiles is limited by factors such as sensor geometry, sample curvature, and diffusion limitation. In this work, we report on high-resolution single-sided NMR scanner measurements with a commercial device, and quantify these limitations. The highest achievable spatial resolution on the used profiler, and the lateral dimension of the sensitive volume were determined. Since articular cartilage samples are usually bent, we also focus on averaging effects inside the horizontally aligned sensitive volume and their impact on the relaxation profiles. Taking these critical parameters into consideration, depth-dependent relaxation time profiles with the maximum achievable vertical resolution of 20 μm are discussed, and are correlated with diffusion coefficient profiles in hyaline articular cartilage in order to reconstruct T2 maps from the diffusion-weighted CPMG decays of apparent relaxation rates.

cisMEP: an integrated repository of genomic epigenetic profiles and cis-regulatory modules in Drosophila.

Science.gov (United States)

Yang, Tzu-Hsien; Wang, Chung-Ching; Hung, Po-Cheng; Wu, Wei-Sheng

2014-01-01

Cis-regulatory modules (CRMs), or the DNA sequences required for regulating gene expression, play the central role in biological researches on transcriptional regulation in metazoan species. Nowadays, the systematic understanding of CRMs still mainly resorts to computational methods due to the time-consuming and small-scale nature of experimental methods. But the accuracy and reliability of different CRM prediction tools are still unclear. Without comparative cross-analysis of the results and combinatorial consideration with extra experimental information, there is no easy way to assess the confidence of the predicted CRMs. This limits the genome-wide understanding of CRMs. It is known that transcription factor binding and epigenetic profiles tend to determine functions of CRMs in gene transcriptional regulation. Thus integration of the genome-wide epigenetic profiles with systematically predicted CRMs can greatly help researchers evaluate and decipher the prediction confidence and possible transcriptional regulatory functions of these potential CRMs. However, these data are still fragmentary in the literatures. Here we performed the computational genome-wide screening for potential CRMs using different prediction tools and constructed the pioneer database, cisMEP (cis-regulatory module epigenetic profile database), to integrate these computationally identified CRMs with genomic epigenetic profile data. cisMEP collects the literature-curated TFBS location data and nine genres of epigenetic data for assessing the confidence of these potential CRMs and deciphering the possible CRM functionality. cisMEP aims to provide a user-friendly interface for researchers to assess the confidence of different potential CRMs and to understand the functions of CRMs through experimentally-identified epigenetic profiles. The deposited potential CRMs and experimental epigenetic profiles for confidence assessment provide experimentally testable hypotheses for the molecular mechanisms

Whole-genome phylogeny of Escherichia coli/Shigella group by feature frequency profiles (FFPs)

Science.gov (United States)

Sims, Gregory E.; Kim, Sung-Hou

2011-01-01

A whole-genome phylogeny of the Escherichia coli/Shigella group was constructed by using the feature frequency profile (FFP) method. This alignment-free approach uses the frequencies of l-mer features of whole genomes to infer phylogenic distances. We present two phylogenies that accentuate different aspects of E. coli/Shigella genomic evolution: (i) one based on the compositions of all possible features of length l = 24 (∼8.4 million features), which are likely to reveal the phenetic grouping and relationship among the organisms and (ii) the other based on the compositions of core features with low frequency and low variability (∼0.56 million features), which account for ∼69% of all commonly shared features among 38 taxa examined and are likely to have genome-wide lineal evolutionary signal. Shigella appears as a single clade when all possible features are used without filtering of noncore features. However, results using core features show that Shigella consists of at least two distantly related subclades, implying that the subclades evolved into a single clade because of a high degree of convergence influenced by mobile genetic elements and niche adaptation. In both FFP trees, the basal group of the E. coli/Shigella phylogeny is the B2 phylogroup, which contains primarily uropathogenic strains, suggesting that the E. coli/Shigella ancestor was likely a facultative or opportunistic pathogen. The extant commensal strains diverged relatively late and appear to be the result of reductive evolution of genomes. We also identify clade distinguishing features and their associated genomic regions within each phylogroup. Such features may provide useful information for understanding evolution of the groups and for quick diagnostic identification of each phylogroup. PMID:21536867

Core Genome Multilocus Sequence Typing Scheme for Stable, Comparative Analyses of Campylobacter jejuni and C. coli Human Disease Isolates.

Science.gov (United States)

Cody, Alison J; Bray, James E; Jolley, Keith A; McCarthy, Noel D; Maiden, Martin C J

2017-07-01

Human campylobacteriosis, caused by Campylobacter jejuni and C. coli , remains a leading cause of bacterial gastroenteritis in many countries, but the epidemiology of campylobacteriosis outbreaks remains poorly defined, largely due to limitations in the resolution and comparability of isolate characterization methods. Whole-genome sequencing (WGS) data enable the improvement of sequence-based typing approaches, such as multilocus sequence typing (MLST), by substantially increasing the number of loci examined. A core genome MLST (cgMLST) scheme defines a comprehensive set of those loci present in most members of a bacterial group, balancing very high resolution with comparability across the diversity of the group. Here we propose a set of 1,343 loci as a human campylobacteriosis cgMLST scheme (v1.0), the allelic profiles of which can be assigned to core genome sequence types. The 1,343 loci chosen were a subset of the 1,643 loci identified in the reannotation of the genome sequence of C. jejuni isolate NCTC 11168, chosen as being present in >95% of draft genomes of 2,472 representative United Kingdom campylobacteriosis isolates, comprising 2,207 (89.3%) C. jejuni isolates and 265 (10.7%) C. coli isolates. Validation of the cgMLST scheme was undertaken with 1,478 further high-quality draft genomes, containing 150 or fewer contiguous sequences, from disease isolate collections: 99.5% of these isolates contained ≥95% of the 1,343 cgMLST loci. In addition to the rapid and effective high-resolution analysis of large numbers of diverse isolates, the cgMLST scheme enabled the efficient identification of very closely related isolates from a well-defined single-source campylobacteriosis outbreak. Copyright © 2017 Cody et al.

Shedding light on cell compartmentation in the candidate phylum Poribacteria by high resolution visualisation and transcriptional profiling

KAUST Repository

Jahn, Martin T.

2016-10-31

Assigning functions to uncultivated environmental microorganisms continues to be a challenging endeavour. Here, we present a new microscopy protocol for fluorescence in situ hybridisation-correlative light and electron microscopy (FISH-CLEM) that enabled, to our knowledge for the first time, the identification of single cells within their complex microenvironment at electron microscopy resolution. Members of the candidate phylum Poribacteria, common and uncultivated symbionts of marine sponges, were used towards this goal. Cellular 3D reconstructions revealed bipolar, spherical granules of low electron density, which likely represent carbon reserves. Poribacterial activity profiles were retrieved from prokaryotic enriched sponge metatranscriptomes using simulation-based optimised mapping. We observed high transcriptional activity for proteins related to bacterial microcompartments (BMC) and we resolved their subcellular localisation by combining FISH-CLEM with immunohistochemistry (IHC) on ultra-thin sponge tissue sections. In terms of functional relevance, we propose that the BMC-A region may be involved in 1,2-propanediol degradation. The FISH-IHC-CLEM approach was proven an effective toolkit to combine -omics approaches with functional studies and it should be widely applicable in environmental microbiology.

High-resolution field shaping utilizing a masked multileaf collimator.

Science.gov (United States)

Williams, P C; Cooper, P

2000-08-01

Multileaf collimators (MLCs) have become an important tool in the modern radiotherapy department. However, the current limit of resolution (1 cm at isocentre) can be too coarse for acceptable shielding of all fields. A number of mini- and micro-MLCs have been developed, with thinner leaves to achieve approved resolution. Currently however, such devices are limited to modest field sizes and stereotactic applications. This paper proposes a new method of high-resolution beam collimation by use of a tertiary grid collimator situated below the conventional MLC. The width of each slit in the grid is a submultiple of the MLC width. A composite shaped field is thus built up from a series of subfields, with the main MLC defining the length of each strip within each subfield. Presented here are initial findings using a prototype device. The beam uniformity achievable with such a device was examined by measuring transmission profiles through the grid using a diode. Profiles thus measured were then copied and superposed to generate composite beams, from which the uniformity achievable could be assessed. With the average dose across the profile normalized to 100%, hot spots up to 5.0% and troughs of 3% were identified for a composite beam of 2 x 5.0 mm grids, as measured at Dmax for a 6 MV beam. For a beam composed from 4 x 2.5 mm grids, the maximum across the profile was 3.0% above the average, and the minimum 2.5% below. Actual composite profiles were also formed using the integrating properties of film, with the subfield indexing performed using an engineering positioning stage. The beam uniformity for these fields compared well with that achieved in theory using the diode measurements. Finally sine wave patterns were generated to demonstrate the potential improvements in field shaping and conformity using this device as opposed to the conventional MLC alone. The scalloping effect on the field edge commonly seen on MLC fields was appreciably reduced by use of 2 x 5.0 mm

Quantitative high dynamic range beam profiling for fluorescence microscopy

International Nuclear Information System (INIS)

Mitchell, T. J.; Saunter, C. D.; O’Nions, W.; Girkin, J. M.; Love, G. D.

2014-01-01

Modern developmental biology relies on optically sectioning fluorescence microscope techniques to produce non-destructive in vivo images of developing specimens at high resolution in three dimensions. As optimal performance of these techniques is reliant on the three-dimensional (3D) intensity profile of the illumination employed, the ability to directly record and analyze these profiles is of great use to the fluorescence microscopist or instrument builder. Though excitation beam profiles can be measured indirectly using a sample of fluorescent beads and recording the emission along the microscope detection path, we demonstrate an alternative approach where a miniature camera sensor is used directly within the illumination beam. Measurements taken using our approach are solely concerned with the illumination optics as the detection optics are not involved. We present a miniature beam profiling device and high dynamic range flux reconstruction algorithm that together are capable of accurately reproducing quantitative 3D flux maps over a large focal volume. Performance of this beam profiling system is verified within an optical test bench and demonstrated for fluorescence microscopy by profiling the low NA illumination beam of a single plane illumination microscope. The generality and success of this approach showcases a widely flexible beam amplitude diagnostic tool for use within the life sciences

Emerging applications of read profiles towards the functional annotation of the genome

DEFF Research Database (Denmark)

Pundhir, Sachin; Poirazi, Panayiota; Gorodkin, Jan

2015-01-01

is typically a result of the protocol designed to address specific research questions. The sequencing results in reads, which when mapped to a reference genome often leads to the formation of distinct patterns (read profiles). Interpretation of these read profiles is essential for their analysis in relation...... to the research question addressed. Several strategies have been employed at varying levels of abstraction ranging from a somewhat ad hoc to a more systematic analysis of read profiles. These include methods which can compare read profiles, e.g., from direct (non-sequence based) alignments to classification...... of patterns into functional groups. In this review, we highlight the emerging applications of read profiles for the annotation of non-coding RNA and cis-regulatory elements (CREs) such as enhancers and promoters. We also discuss the biological rationale behind their formation....

HuH-7 reference genome profile: complex karyotype composed of massive loss of heterozygosity.

Science.gov (United States)

Kasai, Fumio; Hirayama, Noriko; Ozawa, Midori; Satoh, Motonobu; Kohara, Arihiro

2018-05-17

Human cell lines represent a valuable resource as in vitro experimental models. A hepatoma cell line, HuH-7 (JCRB0403), has been used extensively in various research fields and a number of studies using this line have been published continuously since it was established in 1982. However, an accurate genome profile, which can be served as a reliable reference, has not been available. In this study, we performed M-FISH, SNP microarray and amplicon sequencing to characterize the cell line. Single cell analysis of metaphases revealed a high level of heterogeneity with a mode of 60 chromosomes. Cytogenetic results demonstrated chromosome abnormalities involving every chromosome in addition to a massive loss of heterozygosity, which accounts for 55.3% of the genome, consistent with the homozygous variants seen in the sequence analysis. We provide empirical data that the HuH-7 cell line is composed of highly heterogeneous cell populations, suggesting that besides cell line authentication, the quality of cell lines needs to be taken into consideration in the future use of tumor cell lines.

High-throughput SNP genotyping in the highly heterozygous genome of Eucalyptus: assay success, polymorphism and transferability across species

Science.gov (United States)

2011-01-01

Background High-throughput SNP genotyping has become an essential requirement for molecular breeding and population genomics studies in plant species. Large scale SNP developments have been reported for several mainstream crops. A growing interest now exists to expand the speed and resolution of genetic analysis to outbred species with highly heterozygous genomes. When nucleotide diversity is high, a refined diagnosis of the target SNP sequence context is needed to convert queried SNPs into high-quality genotypes using the Golden Gate Genotyping Technology (GGGT). This issue becomes exacerbated when attempting to transfer SNPs across species, a scarcely explored topic in plants, and likely to become significant for population genomics and inter specific breeding applications in less domesticated and less funded plant genera. Results We have successfully developed the first set of 768 SNPs assayed by the GGGT for the highly heterozygous genome of Eucalyptus from a mixed Sanger/454 database with 1,164,695 ESTs and the preliminary 4.5X draft genome sequence for E. grandis. A systematic assessment of in silico SNP filtering requirements showed that stringent constraints on the SNP surrounding sequences have a significant impact on SNP genotyping performance and polymorphism. SNP assay success was high for the 288 SNPs selected with more rigorous in silico constraints; 93% of them provided high quality genotype calls and 71% of them were polymorphic in a diverse panel of 96 individuals of five different species. SNP reliability was high across nine Eucalyptus species belonging to three sections within subgenus Symphomyrtus and still satisfactory across species of two additional subgenera, although polymorphism declined as phylogenetic distance increased. Conclusions This study indicates that the GGGT performs well both within and across species of Eucalyptus notwithstanding its nucleotide diversity ≥2%. The development of a much larger array of informative SNPs across

High resolution infrared spectroscopy of symbiotic stars

International Nuclear Information System (INIS)

Bensammar, S.

1989-01-01

We report here very early results of high resolution (5x10 3 - 4x10 4 ) infrared spectroscopy (1 - 2.5 μm) of different symbiotic stars (T CrB, RW Hya, CI Cyg, PU Vul) observed with the Fourier Transform Spectrometer of the 3.60m Canada France Hawaii Telescope. These stars are usually considered as interacting binaries and only little details are known about the nature of their cool component. CO absorption lines are detected for the four stars. Very different profiles of hydrogen Brackett γ and helium 10830 A lines are shown for CI Cyg observed at different phases, while Pu Vul shows very intense emission lines

Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

Directory of Open Access Journals (Sweden)

Jingsong Shi

2016-01-01

Full Text Available Objective. To investigate potential drugs for diabetic nephropathy (DN using whole-genome expression profiles and the Connectivity Map (CMAP. Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods. Results. (1 A total of 1065 DEGs (FDR 1.5 were found in late stage DN patients compared with early stage DN patients. (2 Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2, vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-κB inhibitors, histone deacetylase inhibitors (HDACIs, PI3K pathway inhibitors, or PPARγ agonists, respectively. Conclusion. Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

A high-resolution and observationally constrained OMI NO2 satellite retrieval

International Nuclear Information System (INIS)

Goldberg, Daniel L.; Lamsal, Lok N.; Loughner, Christopher P.

2017-01-01

Here, this work presents a new high-resolution NO 2 dataset derived from the NASA Ozone Monitoring Instrument (OMI) NO 2 version 3.0 retrieval that can be used to estimate surface-level concentrations. The standard NASA product uses NO 2 vertical profile shape factors from a 1.25° × 1° (~110 km × 110 km) resolution Global Model Initiative (GMI) model simulation to calculate air mass factors, a critical value used to determine observed tropospheric NO 2 vertical columns. To better estimate vertical profile shape factors, we use a high-resolution (1.33 km × 1.33 km) Community Multi-scale Air Quality (CMAQ) model simulation constrained by in situ aircraft observations to recalculate tropospheric air mass factors and tropospheric NO 2 vertical columns during summertime in the eastern US. In this new product, OMI NO 2 tropospheric columns increase by up to 160% in city centers and decrease by 20–50 % in the rural areas outside of urban areas when compared to the operational NASA product. Our new product shows much better agreement with the Pandora NO 2 and Airborne Compact Atmospheric Mapper (ACAM) NO 2 spectrometer measurements acquired during the DISCOVER-AQ Maryland field campaign. Furthermore, the correlation between our satellite product and EPA NO 2 monitors in urban areas has improved dramatically: r 2 = 0.60 in the new product vs. r 2 = 0.39 in the operational product, signifying that this new product is a better indicator of surface concentrations than the operational product. Our work emphasizes the need to use both high-resolution and high-fidelity models in order to recalculate satellite data in areas with large spatial heterogeneities in NO x emissions. Although the current work is focused on the eastern US, the methodology developed in this work can be applied to other world regions to produce high-quality region-specific NO 2 satellite retrievals.

High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia

OpenAIRE

Drewes, Julia L.; White, James R.; Dejea, Christine M.; Fathi, Payam; Iyadorai, Thevambiga; Vadivelu, Jamuna; Roslani, April C.; Wick, Elizabeth C.; Mongodin, Emmanuel F.; Loke, Mun Fai; Thulasi, Kumar; Gan, Han Ming; Goh, Khean Lee; Chong, Hoong Yin; Kumar, Sandip

2017-01-01

Colorectal cancer (CRC) remains the third most common cancer worldwide, with a growing incidence among young adults. Multiple studies have presented associations between the gut microbiome and CRC, suggesting a link with cancer risk. Although CRC microbiome studies continue to profile larger patient cohorts with increasingly economical and rapid DNA sequencing platforms, few common associations with CRC have been identified, in part due to limitations in taxonomic resolution and differences i...

Whole genome DNA copy number changes identified by high density oligonucleotide arrays

Directory of Open Access Journals (Sweden)

Huang Jing

2004-05-01

Full Text Available Abstract Changes in DNA copy number are one of the hallmarks of the genetic instability common to most human cancers. Previous micro-array-based methods have been used to identify chromosomal gains and losses; however, they are unable to genotype alleles at the level of single nucleotide polymorphisms (SNPs. Here we describe a novel algorithm that uses a recently developed high-density oligonucleotide array-based SNP genotyping method, whole genome sampling analysis (WGSA, to identify genome-wide chromosomal gains and losses at high resolution. WGSA simultaneously genotypes over 10,000 SNPs by allele-specific hybridisation to perfect match (PM and mismatch (MM probes synthesised on a single array. The copy number algorithm jointly uses PM intensity and discrimination ratios between paired PM and MM intensity values to identify and estimate genetic copy number changes. Values from an experimental sample are compared with SNP-specific distributions derived from a reference set containing over 100 normal individuals to gain statistical power. Genomic regions with statistically significant copy number changes can be identified using both single point analysis and contiguous point analysis of SNP intensities. We identified multiple regions of amplification and deletion using a panel of human breast cancer cell lines. We verified these results using an independent method based on quantitative polymerase chain reaction and found that our approach is both sensitive and specific and can tolerate samples which contain a mixture of both tumour and normal DNA. In addition, by using known allele frequencies from the reference set, statistically significant genomic intervals can be identified containing contiguous stretches of homozygous markers, potentially allowing the detection of regions undergoing loss of heterozygosity (LOH without the need for a matched normal control sample. The coupling of LOH analysis, via SNP genotyping, with copy number

The Next-generation Berkeley High Resolution NO2 (BEHR NO2) Retrieval: Design and Preliminary Emissions Constraints

Science.gov (United States)

Laughner, J.; Cohen, R. C.

2017-12-01

Recent work has identified a number of assumptions made in NO2 retrievals that lead to biases in the retrieved NO2 column density. These include the treatment of the surface as an isotropic reflector, the absence of lightning NO2 in high resolution a priori profiles, and the use of monthly averaged a priori profiles. We present a new release of the Berkeley High Resolution (BEHR) OMI NO2 retrieval based on the new NASA Standard Product (version 3) that addresses these assumptions by: accounting for surface anisotropy by using a BRDF albedo product, using an updated method of regridding NO2 data, and revised NO2 a priori profiles that better account for lightning NO2 and daily variation in the profile shape. We quantify the effect these changes have on the retrieved NO2 column densities and the resultant impact these updates have on constraints of urban NOx emissions for select cities throughout the United States.

Using Moderate-Resolution Temporal NDVI Profiles for High-Resolution Crop Mapping in Years of Absent Ground Reference Data: A Case Study of Bole and Manas Counties in Xinjiang, China

Directory of Open Access Journals (Sweden)

Pengyu Hao

2016-05-01

Full Text Available Most methods used for crop classification rely on the ground-reference data of the same year, which leads to considerable financial and labor cost. In this study, we presented a method that can avoid the requirements of a large number of ground-reference data in the classification year. Firstly, we extracted the Normalized Difference Vegetation Index (NDVI time series profiles of the dominant crops from MODIS data using the historical ground-reference data in multiple years (2006, 2007, 2009 and 2010. Artificial Antibody Network (ABNet was then employed to build reference NDVI time series for each crop based on the historical NDVI profiles. Afterwards, images of Landsat and HJ were combined to obtain 30 m image time series with 15-day acquisition frequency in 2011. Next, the reference NDVI time series were transformed to Landsat/HJ NDVI time series using their linear model. Finally, the transformed reference NDVI profiles were used to identify the crop types in 2011 at 30 m spatial resolution. The result showed that the dominant crops could be identified with overall accuracy of 87.13% and 83.48% in Bole and Manas, respectively. In addition, the reference NDVI profiles generated from multiple years could achieve better classification accuracy than that from single year (such as only 2007. This is mainly because the reference knowledge from multiple years contains more growing conditions of the same crop. Generally, this approach showed potential to identify crops without using large number of ground-reference data at 30 m resolution.

Genome-wide expression profiling of complex regional pain syndrome.

Directory of Open Access Journals (Sweden)

Eun-Heui Jin

Full Text Available Complex regional pain syndrome (CRPS is a chronic, progressive, and devastating pain syndrome characterized by spontaneous pain, hyperalgesia, allodynia, altered skin temperature, and motor dysfunction. Although previous gene expression profiling studies have been conducted in animal pain models, there genome-wide expression profiling in the whole blood of CRPS patients has not been reported yet. Here, we successfully identified certain pain-related genes through genome-wide expression profiling in the blood from CRPS patients. We found that 80 genes were differentially expressed between 4 CRPS patients (2 CRPS I and 2 CRPS II and 5 controls (cut-off value: 1.5-fold change and p<0.05. Most of those genes were associated with signal transduction, developmental processes, cell structure and motility, and immunity and defense. The expression levels of major histocompatibility complex class I A subtype (HLA-A29.1, matrix metalloproteinase 9 (MMP9, alanine aminopeptidase N (ANPEP, l-histidine decarboxylase (HDC, granulocyte colony-stimulating factor 3 receptor (G-CSF3R, and signal transducer and activator of transcription 3 (STAT3 genes selected from the microarray were confirmed in 24 CRPS patients and 18 controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR. We focused on the MMP9 gene that, by qRT-PCR, showed a statistically significant difference in expression in CRPS patients compared to controls with the highest relative fold change (4.0±1.23 times and p = 1.4×10(-4. The up-regulation of MMP9 gene in the blood may be related to the pain progression in CRPS patients. Our findings, which offer a valuable contribution to the understanding of the differential gene expression in CRPS may help in the understanding of the pathophysiology of CRPS pain progression.

High-throughput sequencing of three Lemnoideae (duckweeds chloroplast genomes from total DNA.

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Wenqin Wang

Full Text Available BACKGROUND: Chloroplast genomes provide a wealth of information for evolutionary and population genetic studies. Chloroplasts play a particularly important role in the adaption for aquatic plants because they float on water and their major surface is exposed continuously to sunlight. The subfamily of Lemnoideae represents such a collection of aquatic species that because of photosynthesis represents one of the fastest growing plant species on earth. METHODS: We sequenced the chloroplast genomes from three different genera of Lemnoideae, Spirodela polyrhiza, Wolffiella lingulata and Wolffia australiana by high-throughput DNA sequencing of genomic DNA using the SOLiD platform. Unfractionated total DNA contains high copies of plastid DNA so that sequences from the nucleus and mitochondria can easily be filtered computationally. Remaining sequence reads were assembled into contiguous sequences (contigs using SOLiD software tools. Contigs were mapped to a reference genome of Lemna minor and gaps, selected by PCR, were sequenced on the ABI3730xl platform. CONCLUSIONS: This combinatorial approach yielded whole genomic contiguous sequences in a cost-effective manner. Over 1,000-time coverage of chloroplast from total DNA were reached by the SOLiD platform in a single spot on a quadrant slide without purification. Comparative analysis indicated that the chloroplast genome was conserved in gene number and organization with respect to the reference genome of L. minor. However, higher nucleotide substitution, abundant deletions and insertions occurred in non-coding regions of these genomes, indicating a greater genomic dynamics than expected from the comparison of other related species in the Pooideae. Noticeably, there was no transition bias over transversion in Lemnoideae. The data should have immediate applications in evolutionary biology and plant taxonomy with increased resolution and statistical power.

Chromosomal Localization of DNA Amplifications in Neuroblastoma Tumors Using cDNA Microarray Comparative Genomic Hybridization

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Ben Beheshti

2003-01-01

Full Text Available Conventional comparative genomic hybridization (CGH profiling of neuroblastomas has identified many genomic aberrations, although the limited resolution has precluded a precise localization of sequences of interest within amplicons. To map high copy number genomic gains in clinically matched stage IV neuroblastomas, CGH analysis using a 19,200-feature cDNA microarray was used. A dedicated (freely available algorithm was developed for rapid in silico determination of chromosomal localizations of microarray cDNA targets, and for generation of an ideogram-type profile of copy number changes. Using these methodologies, novel gene amplifications undetectable by chromosome CGH were identified, and larger MYCN amplicon sizes (in one tumor up to 6 Mb than those previously reported in neuroblastoma were identified. The genes HPCAL1, LPIN1/KIAA0188, NAG, and NSE1/LOC151354 were found to be coamplified with MYCN. To determine whether stage IV primary tumors could be further subclassified based on their genomic copy number profiles, hierarchical clustering was performed. Cluster analysis of microarray CGH data identified three groups: 1 no amplifications evident, 2 a small MYCN amplicon as the only detectable imbalance, and 3 a large MYCN amplicon with additional gene amplifications. Application of CGH to cDNA microarray targets will help to determine both the variation of amplicon size and help better define amplification-dependent and independent pathways of progression in neuroblastoma.

Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale

DEFF Research Database (Denmark)

Liu, Siyang; Huang, Shujia; Rao, Junhua

2015-01-01

present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome......) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism. We...... assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity. Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction...

Unprecedented high-resolution view of bacterial operon architecture revealed by RNA sequencing.

Science.gov (United States)

Conway, Tyrrell; Creecy, James P; Maddox, Scott M; Grissom, Joe E; Conkle, Trevor L; Shadid, Tyler M; Teramoto, Jun; San Miguel, Phillip; Shimada, Tomohiro; Ishihama, Akira; Mori, Hirotada; Wanner, Barry L

2014-07-08

We analyzed the transcriptome of Escherichia coli K-12 by strand-specific RNA sequencing at single-nucleotide resolution during steady-state (logarithmic-phase) growth and upon entry into stationary phase in glucose minimal medium. To generate high-resolution transcriptome maps, we developed an organizational schema which showed that in practice only three features are required to define operon architecture: the promoter, terminator, and deep RNA sequence read coverage. We precisely annotated 2,122 promoters and 1,774 terminators, defining 1,510 operons with an average of 1.98 genes per operon. Our analyses revealed an unprecedented view of E. coli operon architecture. A large proportion (36%) of operons are complex with internal promoters or terminators that generate multiple transcription units. For 43% of operons, we observed differential expression of polycistronic genes, despite being in the same operons, indicating that E. coli operon architecture allows fine-tuning of gene expression. We found that 276 of 370 convergent operons terminate inefficiently, generating complementary 3' transcript ends which overlap on average by 286 nucleotides, and 136 of 388 divergent operons have promoters arranged such that their 5' ends overlap on average by 168 nucleotides. We found 89 antisense transcripts of 397-nucleotide average length, 7 unannotated transcripts within intergenic regions, and 18 sense transcripts that completely overlap operons on the opposite strand. Of 519 overlapping transcripts, 75% correspond to sequences that are highly conserved in E. coli (>50 genomes). Our data extend recent studies showing unexpected transcriptome complexity in several bacteria and suggest that antisense RNA regulation is widespread. Importance: We precisely mapped the 5' and 3' ends of RNA transcripts across the E. coli K-12 genome by using a single-nucleotide analytical approach. Our resulting high-resolution transcriptome maps show that ca. one-third of E. coli operons are

High-Resolution Patterns of Meiotic Recombination across the Human Major Histocompatibility Complex

Science.gov (United States)

Cullen, Michael; Perfetto, Stephen P.; Klitz, William; Nelson, George; Carrington, Mary

2002-01-01

Definitive characteristics of meiotic recombination events over large (i.e., >1 Mb) segments of the human genome remain obscure, yet they are essential for establishing the haplotypic structure of the genome and for efficient mapping of complex traits. We present a high-resolution map of recombination at the kilobase level across a 3.3-Mb interval encompassing the major histocompatibility complex (MHC). Genotyping of 20,031 single sperm from 12 individuals resulted in the identification and fine mapping of 325 recombinant chromosomes within genomic intervals as small as 7 kb. Several principal characteristics of recombination in this region were observed: (1) rates of recombination can differ significantly between individuals; (2) intense hot spots of recombination occur at least every 0.8 Mb but are not necessarily evenly spaced; (3) distribution in the location of recombination events can differ significantly among individuals; (4) between hot spots, low levels of recombination occur fairly evenly across 100-kb segments, suggesting the presence of warm spots of recombination; and (5) specific sequence motifs associate significantly with recombination distribution. These data provide a plausible model for recombination patterns of the human genome overall. PMID:12297984

Comparing genome-wide chromatin profiles using ChIP-chip or ChIP-seq

NARCIS (Netherlands)

Johannes, F.; Wardenaar, R.; Colome-Tatche, M.; Mousson, F.; de Graaf, P.; Mokry, M.; Guryev, V.; Timmers, H.T.; Cuppen, E.; Jansen, R.

2010-01-01

MOTIVATION: ChIP-chip and ChIP-seq technologies provide genome-wide measurements of various types of chromatin marks at an unprecedented resolution. With ChIP samples collected from different tissue types and/or individuals, we can now begin to characterize stochastic or systematic changes in

Depth of interaction resolution measurements for a high resolution PET detector using position sensitive avalanche photodiodes

International Nuclear Information System (INIS)

Yang Yongfeng; Dokhale, Purushottam A; Silverman, Robert W; Shah, Kanai S; McClish, Mickel A; Farrell, Richard; Entine, Gerald; Cherry, Simon R

2006-01-01

We explore dual-ended read out of LSO arrays with two position sensitive avalanche photodiodes (PSAPDs) as a high resolution, high efficiency depth-encoding detector for PET applications. Flood histograms, energy resolution and depth of interaction (DOI) resolution were measured for unpolished LSO arrays with individual crystal sizes of 1.0, 1.3 and 1.5 mm, and for a polished LSO array with 1.3 mm pixels. The thickness of the crystal arrays was 20 mm. Good flood histograms were obtained for all four arrays, and crystals in all four arrays can be clearly resolved. Although the amplitude of each PSAPD signal decreases as the interaction depth moves further from the PSAPD, the sum of the two PSAPD signals is essentially constant with irradiation depth for all four arrays. The energy resolutions were similar for all four arrays, ranging from 14.7% to 15.4%. A DOI resolution of 3-4 mm (including the width of the irradiation band which is ∼2 mm) was obtained for all the unpolished arrays. The best DOI resolution was achieved with the unpolished 1 mm array (average 3.5 mm). The DOI resolution for the 1.3 mm and 1.5 mm unpolished arrays was 3.7 and 4.0 mm respectively. For the polished array, the DOI resolution was only 16.5 mm. Summing the DOI profiles across all crystals for the 1 mm array only degraded the DOI resolution from 3.5 mm to 3.9 mm, indicating that it may not be necessary to calibrate the DOI response separately for each crystal within an array. The DOI response of individual crystals in the array confirms this finding. These results provide a detailed characterization of the DOI response of these PSAPD-based PET detectors which will be important in the design and calibration of a PET scanner making use of this detector approach

CHESS (CgHExpreSS): a comprehensive analysis tool for the analysis of genomic alterations and their effects on the expression profile of the genome.

Science.gov (United States)

Lee, Mikyung; Kim, Yangseok

2009-12-16

Genomic alterations frequently occur in many cancer patients and play important mechanistic roles in the pathogenesis of cancer. Furthermore, they can modify the expression level of genes due to altered copy number in the corresponding region of the chromosome. An accumulating body of evidence supports the possibility that strong genome-wide correlation exists between DNA content and gene expression. Therefore, more comprehensive analysis is needed to quantify the relationship between genomic alteration and gene expression. A well-designed bioinformatics tool is essential to perform this kind of integrative analysis. A few programs have already been introduced for integrative analysis. However, there are many limitations in their performance of comprehensive integrated analysis using published software because of limitations in implemented algorithms and visualization modules. To address this issue, we have implemented the Java-based program CHESS to allow integrative analysis of two experimental data sets: genomic alteration and genome-wide expression profile. CHESS is composed of a genomic alteration analysis module and an integrative analysis module. The genomic alteration analysis module detects genomic alteration by applying a threshold based method or SW-ARRAY algorithm and investigates whether the detected alteration is phenotype specific or not. On the other hand, the integrative analysis module measures the genomic alteration's influence on gene expression. It is divided into two separate parts. The first part calculates overall correlation between comparative genomic hybridization ratio and gene expression level by applying following three statistical methods: simple linear regression, Spearman rank correlation and Pearson's correlation. In the second part, CHESS detects the genes that are differentially expressed according to the genomic alteration pattern with three alternative statistical approaches: Student's t-test, Fisher's exact test and Chi square

Ultra-high resolution protein crystallography

International Nuclear Information System (INIS)

Takeda, Kazuki; Hirano, Yu; Miki, Kunio

2010-01-01

Many protein structures have been determined by X-ray crystallography and deposited with the Protein Data Bank. However, these structures at usual resolution (1.5< d<3.0 A) are insufficient in their precision and quantity for elucidating the molecular mechanism of protein functions directly from structural information. Several studies at ultra-high resolution (d<0.8 A) have been performed with synchrotron radiation in the last decade. The highest resolution of the protein crystals was achieved at 0.54 A resolution for a small protein, crambin. In such high resolution crystals, almost all of hydrogen atoms of proteins and some hydrogen atoms of bound water molecules are experimentally observed. In addition, outer-shell electrons of proteins can be analyzed by the multipole refinement procedure. However, the influence of X-rays should be precisely estimated in order to derive meaningful information from the crystallographic results. In this review, we summarize refinement procedures, current status and perspectives for ultra high resolution protein crystallography. (author)

Edible seaweed as future functional food: Identification of α-glucosidase inhibitors by combined use of high-resolution α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR.

Science.gov (United States)

Liu, Bingrui; Kongstad, Kenneth T; Wiese, Stefanie; Jäger, Anna K; Staerk, Dan

2016-07-15

Crude chloroform, ethanol and acetone extracts of nineteen seaweed species were screened for their antioxidant and α-glucosidase inhibitory activity. Samples showing more than 60% α-glucosidase inhibitory activity, at a concentration of 1 mg/ml, were furthermore investigated using high-resolution α-glucosidase inhibition profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HR-bioassay/HPLC-HRMS-SPE-NMR). The results showed Ascophyllum nodosum and Fucus vesicolosus to be rich in antioxidants, equaling a Trolox equivalent antioxidant capacity of 135 and 108 mM Troloxmg(-1) extract, respectively. HR-bioassay/HPLC-HRMS-SPE-NMR showed the α-glucosidase inhibitory activity of A. nodosum, F. vesoculosus, Laminaria digitata, Laminaria japonica and Undaria pinnatifida to be caused by phlorotannins as well as fatty acids - with oleic acid, linoleic acid and eicosapentaenoic acid being the most potent with IC50 values of 0.069, 0.075 and 0.10 mM, respectively, and showing a mixed-type inhibition mode. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles.

Science.gov (United States)

Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-Yu; Zhang, Xiao-Mei; Song, Da-Feng; Zhang, Chen

2016-08-01

In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate.

Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles* #

Science.gov (United States)

Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-yu; Zhang, Xiao-mei; Song, Da-feng; Zhang, Chen

2016-01-01

Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. Methods: The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). Results: We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Conclusions: Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate. PMID:27487802

High resolution main-ion charge exchange spectroscopy in the DIII-D H-mode pedestal.

Science.gov (United States)

Grierson, B A; Burrell, K H; Chrystal, C; Groebner, R J; Haskey, S R; Kaplan, D H

2016-11-01

A new high spatial resolution main-ion (deuterium) charge-exchange spectroscopy system covering the tokamak boundary region has been installed on the DIII-D tokamak. Sixteen new edge main-ion charge-exchange recombination sightlines have been combined with nineteen impurity sightlines in a tangentially viewing geometry on the DIII-D midplane with an interleaving design that achieves 8 mm inter-channel radial resolution for detailed profiles of main-ion temperature, velocity, charge-exchange emission, and neutral beam emission. At the plasma boundary, we find a strong enhancement of the main-ion toroidal velocity that exceeds the impurity velocity by a factor of two. The unique combination of experimentally measured main-ion and impurity profiles provides a powerful quasi-neutrality constraint for reconstruction of tokamak H-mode pedestals.

HGVA: the Human Genome Variation Archive

OpenAIRE

Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gr?f, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

2017-01-01

Abstract High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic...

Towards real-time metabolic profiling of a biopsy specimen during a surgical operation by 1H high resolution magic angle spinning nuclear magnetic resonance: a case report

Directory of Open Access Journals (Sweden)

Piotto Martial

2012-01-01

Full Text Available Abstract Introduction Providing information on cancerous tissue samples during a surgical operation can help surgeons delineate the limits of a tumoral invasion more reliably. Here, we describe the use of metabolic profiling of a colon biopsy specimen by high resolution magic angle spinning nuclear magnetic resonance spectroscopy to evaluate tumoral invasion during a simulated surgical operation. Case presentation Biopsy specimens (n = 9 originating from the excised right colon of a 66-year-old Caucasian women with an adenocarcinoma were automatically analyzed using a previously built statistical model. Conclusions Metabolic profiling results were in full agreement with those of a histopathological analysis. The time-response of the technique is sufficiently fast for it to be used effectively during a real operation (17 min/sample. Metabolic profiling has the potential to become a method to rapidly characterize cancerous biopsies in the operation theater.

Genomic profiles of lung cancer associated with idiopathic pulmonary fibrosis.

Science.gov (United States)

Hwang, Ji An; Kim, Deokhoon; Chun, Sung-Min; Bae, SooHyun; Song, Joon Seon; Kim, Mi Young; Koo, Hyun Jung; Song, Jin Woo; Kim, Woo Sung; Lee, Jae Cheol; Kim, Hyeong Ryul; Choi, Chang-Min; Jang, Se Jin

2018-01-01

Little is known about the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC by using targeted exome sequencing (OncoPanel version 2) in 35 matched tumour/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed with GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted with CNVkit, with focal events determined by Genomic Identification of Significant Targets in Cancer 2.0, and pathway analysis (KEGG) with DAVID. Germline mutations in TERT (rs2736100, n = 33) and CDKN1A (rs2395655, n = 27) associated with idiopathic pulmonary fibrosis risk were detected in most samples. A total of 410 somatic mutations were identified, with an average of 11.7 per tumour, including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop and 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C > T transitions despite an extensive smoking history in most patients, suggesting a potential association between APOBEC-related mutagenesis and the development of IPF-LC. TP53 (22/35, 62.9%) and BRAF (6/35, 17.1%) were found to be significantly mutated in IPF-LC. Recurrent focal amplifications in three chromosomal loci (3q26.33, 7q31.2, and 12q14.3) and 9p21.3 deletion were identified, and genes associated with the JAK-STAT signalling pathway were significantly amplified in IPF-LC (P = 0.012). This study demonstrates that IPF-LC is genetically characterized by the presence of somatic mutations reflecting a variety of environmental exposures on the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Copyright © 2017

High Resolution Melting Analysis Targeting hsp70 as a Fast and Efficient Method for the Discrimination of Leishmania Species.

Directory of Open Access Journals (Sweden)

Ricardo Andrade Zampieri

2016-02-01

Full Text Available Protozoan parasites of the genus Leishmania cause a large spectrum of clinical manifestations known as Leishmaniases. These diseases are increasingly important public health problems in many countries both within and outside endemic regions. Thus, an accurate differential diagnosis is extremely relevant for understanding epidemiological profiles and for the administration of the best therapeutic protocol.Exploring the High Resolution Melting (HRM dissociation profiles of two amplicons using real time polymerase chain reaction (real-time PCR targeting heat-shock protein 70 coding gene (hsp70 revealed differences that allowed the discrimination of genomic DNA samples of eight Leishmania species found in the Americas, including Leishmania (Leishmania infantum chagasi, L. (L. amazonensis, L. (L. mexicana, L. (Viannia lainsoni, L. (V. braziliensis, L. (V. guyanensis, L. (V. naiffi and L. (V. shawi, and three species found in Eurasia and Africa, including L. (L. tropica, L. (L. donovani and L. (L. major. In addition, we tested DNA samples obtained from standard promastigote culture, naturally infected phlebotomines, experimentally infected mice and clinical human samples to validate the proposed protocol.HRM analysis of hsp70 amplicons is a fast and robust strategy that allowed for the detection and discrimination of all Leishmania species responsible for the Leishmaniases in Brazil and Eurasia/Africa with high sensitivity and accuracy. This method could detect less than one parasite per reaction, even in the presence of host DNA.

High Resolution Melting Analysis Targeting hsp70 as a Fast and Efficient Method for the Discrimination of Leishmania Species.

Science.gov (United States)

Zampieri, Ricardo Andrade; Laranjeira-Silva, Maria Fernanda; Muxel, Sandra Marcia; Stocco de Lima, Ana Carolina; Shaw, Jeffrey Jon; Floeter-Winter, Lucile Maria

2016-02-01

Protozoan parasites of the genus Leishmania cause a large spectrum of clinical manifestations known as Leishmaniases. These diseases are increasingly important public health problems in many countries both within and outside endemic regions. Thus, an accurate differential diagnosis is extremely relevant for understanding epidemiological profiles and for the administration of the best therapeutic protocol. Exploring the High Resolution Melting (HRM) dissociation profiles of two amplicons using real time polymerase chain reaction (real-time PCR) targeting heat-shock protein 70 coding gene (hsp70) revealed differences that allowed the discrimination of genomic DNA samples of eight Leishmania species found in the Americas, including Leishmania (Leishmania) infantum chagasi, L. (L.) amazonensis, L. (L.) mexicana, L. (Viannia) lainsoni, L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) naiffi and L. (V.) shawi, and three species found in Eurasia and Africa, including L. (L.) tropica, L. (L.) donovani and L. (L.) major. In addition, we tested DNA samples obtained from standard promastigote culture, naturally infected phlebotomines, experimentally infected mice and clinical human samples to validate the proposed protocol. HRM analysis of hsp70 amplicons is a fast and robust strategy that allowed for the detection and discrimination of all Leishmania species responsible for the Leishmaniases in Brazil and Eurasia/Africa with high sensitivity and accuracy. This method could detect less than one parasite per reaction, even in the presence of host DNA.

Metabolic profile modifications in milk after enrofloxacin administration studied by liquid chromatography coupled with high resolution mass spectrometry.

Science.gov (United States)

Junza, A; Saurina, J; Barrón, D; Minguillón, C

2016-08-19

High resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was used in the search and identification of metabolites in raw milk from cows medicated with enrofloxacin. Data consisting of m/z features were taken throughout the entire chromatogram of milk samples from medicated animals and were compared with blank samples. Twenty six different compounds were identified. Some of them were attributed to structures related to enrofloxacin while others were dipeptides or tripeptides. Additionally, enrofloxacin was administered in a controlled treatment for three days. Milk was collected daily from the first day of treatment and until four days after in the search for the identified compounds. The obtained data were chemometrically treated by Principal Component Analysis. Samples were classified by this method into three different groups corresponding to days 1-2, day 3 and days 4-7 considering the different concentration profile evolution of metabolites during the days studied. Tentative metabolic pathways were designed to rationalize the presence of the newly identified compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Radiation hybrid maps of the D-genome of Aegilops tauschii and their application in sequence assembly of large and complex plant genomes.

Science.gov (United States)

Kumar, Ajay; Seetan, Raed; Mergoum, Mohamed; Tiwari, Vijay K; Iqbal, Muhammad J; Wang, Yi; Al-Azzam, Omar; Šimková, Hana; Luo, Ming-Cheng; Dvorak, Jan; Gu, Yong Q; Denton, Anne; Kilian, Andrzej; Lazo, Gerard R; Kianian, Shahryar F

2015-10-16

The large and complex genome of bread wheat (Triticum aestivum L., ~17 Gb) requires high resolution genome maps with saturated marker scaffolds to anchor and orient BAC contigs/ sequence scaffolds for whole genome assembly. Radiation hybrid (RH) mapping has proven to be an excellent tool for the development of such maps for it offers much higher and more uniform marker resolution across the length of the chromosome compared to genetic mapping and does not require marker polymorphism per se, as it is based on presence (retention) vs. absence (deletion) marker assay. In this study, a 178 line RH panel was genotyped with SSRs and DArT markers to develop the first high resolution RH maps of the entire D-genome of Ae. tauschii accession AL8/78. To confirm map order accuracy, the AL8/78-RH maps were compared with:1) a DArT consensus genetic map constructed using more than 100 bi-parental populations, 2) a RH map of the D-genome of reference hexaploid wheat 'Chinese Spring', and 3) two SNP-based genetic maps, one with anchored D-genome BAC contigs and another with anchored D-genome sequence scaffolds. Using marker sequences, the RH maps were also anchored with a BAC contig based physical map and draft sequence of the D-genome of Ae. tauschii. A total of 609 markers were mapped to 503 unique positions on the seven D-genome chromosomes, with a total map length of 14,706.7 cR. The average distance between any two marker loci was 29.2 cR which corresponds to 2.1 cM or 9.8 Mb. The average mapping resolution across the D-genome was estimated to be 0.34 Mb (Mb/cR) or 0.07 cM (cM/cR). The RH maps showed almost perfect agreement with several published maps with regard to chromosome assignments of markers. The mean rank correlations between the position of markers on AL8/78 maps and the four published maps, ranged from 0.75 to 0.92, suggesting a good agreement in marker order. With 609 mapped markers, a total of 2481 deletions for the whole D-genome were detected with an average

Development of high-resolution x-ray CT system using parallel beam geometry

Energy Technology Data Exchange (ETDEWEB)

Yoneyama, Akio, E-mail: akio.yoneyama.bu@hitachi.com; Baba, Rika [Central Research Laboratory, Hitachi Ltd., Hatoyama, Saitama (Japan); Hyodo, Kazuyuki [Institute of Materials Science, High Energy Accelerator Research Organization, Tsukuba, Ibaraki (Japan); Takeda, Tohoru [School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa (Japan); Nakano, Haruhisa; Maki, Koutaro [Department of Orthodontics, School of Dentistry Showa University, Ota-ku, Tokyo (Japan); Sumitani, Kazushi; Hirai, Yasuharu [Kyushu Synchrotron Light Research Center, Tosu, Saga (Japan)

2016-01-28

For fine three-dimensional observations of large biomedical and organic material samples, we developed a high-resolution X-ray CT system. The system consists of a sample positioner, a 5-μm scintillator, microscopy lenses, and a water-cooled sCMOS detector. Parallel beam geometry was adopted to attain a field of view of a few mm square. A fine three-dimensional image of birch branch was obtained using a 9-keV X-ray at BL16XU of SPring-8 in Japan. The spatial resolution estimated from the line profile of a sectional image was about 3 μm.

Triacylglycerol profiling of microalgae strains for biofuel feedstock by liquid chromatography-high-resolution mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

MacDougall, Karen M.; McNichol, Jesse; McGinn, Patrick J.; O' Leary, Stephen J.B.; Melanson, Jeremy E. [Institute for Marine Biosciences, National Research Council of Canada, Halifax, NS (Canada)

2011-11-15

Biofuels from photosynthetic microalgae are quickly gaining interest as a viable carbon-neutral energy source. Typically, characterization of algal feedstock involves breaking down triacylglycerols (TAG) and other intact lipids, followed by derivatization of the fatty acids to fatty acid methyl esters prior to analysis by gas chromatography (GC). However, knowledge of the intact lipid profile could offer significant advantages for discovery stage biofuel research such as the selection of an algal strain or the optimization of growth and extraction conditions. Herein, lipid extracts from microalgae were directly analyzed by ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) using a benchtop Orbitrap mass spectrometer. Phospholipids, glycolipids, and TAGs were analyzed in the same chromatographic run, using a combination of accurate mass and diagnostic fragment ions for identification. Using this approach, greater than 100 unique TAGs were identified over the six algal strains studied and TAG profiles were obtained to assess their potential for biofuel applications. Under the growth conditions employed, Botryococcus braunii and Scenedesmus obliquus yielded the most comprehensive TAG profile with a high abundance of TAGs containing oleic acid. (orig.)

A Novel, Aqueous Surface Treatment To Thermally Stabilize High Resolution Positive Photoresist Images*

Science.gov (United States)

Grunwald, John J.; Spencer, Allen C.

1986-07-01

The paper describes a new approach to thermally stabilize the already imaged profile of high resolution positive photoresists such as ULTRAMAC" PR-914. ***XD-4000, an aqueous emulsion of a blend of fluorine-bearing compounds is spun on top of the developed, positive photoresist-imaged wafer, and baked. This allows the photoresist to withstand temperatures up to at least 175 deg. C. while essentially maintaining vertical edge profiles. Also, adverse effects of "outgassing" in harsh environments, ie., plasma and ion implant are greatly minimized by allowing the high resolution imaged photoresist to be post-baked at "elevated" temperatures. Another type of product that accomplishes the same effect is ***XD-4005, an aqueous emulsion of a high temperature-resistant polymer. While the exact mechanism is yet to be identified, it is postulated that absorption of the "polymeric" species into the "skin" of the imaged resist forms a temperature resistant "envelope", thereby allowing high resolution photoresists to also serve in a "high temperature" mode, without reticulation, or other adverse effects due to thermal degradation. SEM's are presented showing imaged ULTRAMAC" PR-914 and ULTRAMAC" **EPA-914 geometries coated with XD-4000 or XD-4005 and followed by plasma etched oxide,polysilicon and aluminum. Selectivity ratios are compared with and without the novel treatment and are shown to be significantly better with the treatment. The surface-treated photoresist for thermal resistance remains easily strippable in solvent-based or plasma media, unlike photoresists that have undergone "PRIST" or other gaseous thermal stabilization methods.

High throughtput comparisons and profiling of metagenomes for industrially relevant enzymes

KAUST Repository

Alam, Intikhab

2016-01-26

More and more genomes and metagenomes are being sequenced since the advent of Next Generation Sequencing Technologies (NGS). Many metagenomic samples are collected from a variety of environments, each exhibiting a different environmental profile, e.g. temperature, environmental chemistry, etc… These metagenomes can be profiled to unearth enzymes relevant to several industries based on specific enzyme properties such as ability to work on extreme conditions, such as extreme temperatures, salinity, anaerobically, etc.. In this work, we present the DMAP platform comprising of a high-throughput metagenomic annotation pipeline and a data-warehouse for comparisons and profiling across large number of metagenomes. We developed two reference databases for profiling of important genes, one containing enzymes related to different industries and the other containing genes with potential bioactivity roles. In this presentation we describe an example analysis of a large number of publicly available metagenomic sample from TARA oceans study (Science 2015) that covers significant part of world oceans.

High resolution solar observations

International Nuclear Information System (INIS)

Title, A.

1985-01-01

Currently there is a world-wide effort to develop optical technology required for large diffraction limited telescopes that must operate with high optical fluxes. These developments can be used to significantly improve high resolution solar telescopes both on the ground and in space. When looking at the problem of high resolution observations it is essential to keep in mind that a diffraction limited telescope is an interferometer. Even a 30 cm aperture telescope, which is small for high resolution observations, is a big interferometer. Meter class and above diffraction limited telescopes can be expected to be very unforgiving of inattention to details. Unfortunately, even when an earth based telescope has perfect optics there are still problems with the quality of its optical path. The optical path includes not only the interior of the telescope, but also the immediate interface between the telescope and the atmosphere, and finally the atmosphere itself

High speed, High resolution terahertz spectrometers

International Nuclear Information System (INIS)

Kim, Youngchan; Yee, Dae Su; Yi, Miwoo; Ahn, Jaewook

2008-01-01

A variety of sources and methods have been developed for terahertz spectroscopy during almost two decades. Terahertz time domain spectroscopy (THz TDS)has attracted particular attention as a basic measurement method in the fields of THz science and technology. Recently, asynchronous optical sampling (AOS)THz TDS has been demonstrated, featuring rapid data acquisition and a high spectral resolution. Also, terahertz frequency comb spectroscopy (TFCS)possesses attractive features for high precision terahertz spectroscopy. In this presentation, we report on these two types of terahertz spectrometer. Our high speed, high resolution terahertz spectrometer is demonstrated using two mode locked femtosecond lasers with slightly different repetition frequencies without a mechanical delay stage. The repetition frequencies of the two femtosecond lasers are stabilized by use of two phase locked loops sharing the same reference oscillator. The time resolution of our terahertz spectrometer is measured using the cross correlation method to be 270 fs. AOS THz TDS is presented in Fig. 1, which shows a time domain waveform rapidly acquired on a 10ns time window. The inset shows a zoom into the signal with 100ps time window. The spectrum obtained by the fast Fourier Transformation (FFT)of the time domain waveform has a frequency resolution of 100MHz. The dependence of the signal to noise ratio (SNR)on the measurement time is also investigated

Assessment of whole genome amplification-induced bias through high-throughput, massively parallel whole genome sequencing

Directory of Open Access Journals (Sweden)

Plant Ramona N

2006-08-01

Full Text Available Abstract Background Whole genome amplification is an increasingly common technique through which minute amounts of DNA can be multiplied to generate quantities suitable for genetic testing and analysis. Questions of amplification-induced error and template bias generated by these methods have previously been addressed through either small scale (SNPs or large scale (CGH array, FISH methodologies. Here we utilized whole genome sequencing to assess amplification-induced bias in both coding and non-coding regions of two bacterial genomes. Halobacterium species NRC-1 DNA and Campylobacter jejuni were amplified by several common, commercially available protocols: multiple displacement amplification, primer extension pre-amplification and degenerate oligonucleotide primed PCR. The amplification-induced bias of each method was assessed by sequencing both genomes in their entirety using the 454 Sequencing System technology and comparing the results with those obtained from unamplified controls. Results All amplification methodologies induced statistically significant bias relative to the unamplified control. For the Halobacterium species NRC-1 genome, assessed at 100 base resolution, the D-statistics from GenomiPhi-amplified material were 119 times greater than those from unamplified material, 164.0 times greater for Repli-G, 165.0 times greater for PEP-PCR and 252.0 times greater than the unamplified controls for DOP-PCR. For Campylobacter jejuni, also analyzed at 100 base resolution, the D-statistics from GenomiPhi-amplified material were 15 times greater than those from unamplified material, 19.8 times greater for Repli-G, 61.8 times greater for PEP-PCR and 220.5 times greater than the unamplified controls for DOP-PCR. Conclusion Of the amplification methodologies examined in this paper, the multiple displacement amplification products generated the least bias, and produced significantly higher yields of amplified DNA.

High Resolution Shear Profile Measurements in Entangled Polymers

KAUST Repository

Hayes, Keesha A.

2008-11-17

We use confocal microscopy and particle image velocimetry to visualize motion of 250-300 nm. fluorescent tracer particles in entangled polymers subject to a rectilinear shear flow. Our results show linear velocity profiles in polymer solutions spanning a wide range of molecular weights and number of entanglements (8≤Z≤56), but reveal large differences between the imposed and measured shear rates. These findings disagree with recent reports that shear banding is a characteristic flow response of entangled polymers, and instead point to interfacial slip as an important source of strain loss. © 2008 The American Physical Society.

High-Resolution Sonars: What Resolution Do We Need for Target Recognition?

Directory of Open Access Journals (Sweden)

Pailhas Yan

2010-01-01

Full Text Available Target recognition in sonar imagery has long been an active research area in the maritime domain, especially in the mine-counter measure context. Recently it has received even more attention as new sensors with increased resolution have been developed; new threats to critical maritime assets and a new paradigm for target recognition based on autonomous platforms have emerged. With the recent introduction of Synthetic Aperture Sonar systems and high-frequency sonars, sonar resolution has dramatically increased and noise levels decreased. Sonar images are distance images but at high resolution they tend to appear visually as optical images. Traditionally algorithms have been developed specifically for imaging sonars because of their limited resolution and high noise levels. With high-resolution sonars, algorithms developed in the image processing field for natural images become applicable. However, the lack of large datasets has hampered the development of such algorithms. Here we present a fast and realistic sonar simulator enabling development and evaluation of such algorithms.We develop a classifier and then analyse its performances using our simulated synthetic sonar images. Finally, we discuss sensor resolution requirements to achieve effective classification of various targets and demonstrate that with high resolution sonars target highlight analysis is the key for target recognition.

MBARI Mapping AUV: A High-Resolution Deep Ocean Seafloor Mapping Capability

Science.gov (United States)

Caress, D. W.; Kirkwood, W. J.; Thomas, H.; McEwen, R.; Henthorn, R.; McGill, P.; Thompson, D.; Sibenac, M.; Jensen, S.; Shane, F.; Hamilton, A.

2005-05-01

The Monterey Bay Aquarium Research Institute (MBARI) is developing an autonomous seafloor mapping capability for deep ocean science applications. The MBARI Mapping AUV is a 0.53 m (21 in) diameter, 5.1 m (16.7 ft) long, Dorado-class vehicle designed to carry four mapping sonars. The primary sensor is a 200 kHz multibeam sonar producing swath bathymetry and sidescan. In addition, the vehicle carries 100 kHz and 410 kHz chirp sidescan sonars, and a 2-16 kHz sweep chirp subbottom profiler. Navigation and attitude data are obtained from an inertial navigation system (INS) incorporating a ring laser gyro and a 300 kHz Doppler velocity log (DVL). The vehicle also includes acoustic modem, ultra-short baseline navigation, and long-baseline navigation systems. The Mapping AUV is powered by 6 kWhr of Li-polymer batteries, providing expected mission duration of 12 hours at a typical speed of 1.5 m/s. All components of the vehicle are rated to 6000 m depth, allowing MBARI to conduct high-resolution mapping of the deep-ocean seafloor. The sonar package is also be mountable on ROV Ventana, allowing surveys at altitudes less than 20 m at topographically challenging sites. The vehicle was assembled and extensively tested during 2004; this year we are commencing operations for MBARI science projects while continuing the process of testing and integrating the complete suite of sensors and systems. MBARI is beginning to use this capability to observe the changing morphology of dynamic systems such as submarine canyons and active slumps, to map deep-water benthic habitats at resolutions comparable to ROV and submersible observations, to provide basemaps for ROV dives, and to provide high resolution bathymetry and subbottom profiles as part of a variety of projects requiring knowledge of the seafloor. We will present initial results from surveys in and around Monterey Canyon, including high resolution repeat surveys of four sites along the canyon axis.

Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium.

Science.gov (United States)

Machado, Henrique; Gram, Lone

2017-01-01

Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur , amino-acid usage, ANI), which allowed us to identify two misidentified strains. Genome analyses also revealed occurrence of higher and lower GC content clades, correlating with phylogenetic clusters. Pan- and core-genome analysis revealed the conservation of 25% of the genome throughout the genus, with a large and open pan-genome. The major source of genomic diversity could be traced to the smaller chromosome and plasmids. Several of the physiological traits studied in the genus did not correlate with phylogenetic data. Since horizontal gene transfer (HGT) is often suggested as a source of genetic diversity and a potential driver of genomic evolution in bacterial species, we looked into evidence of such in Photobacterium genomes. Genomic islands were the source of genomic differences between strains of the same species. Also, we found transposase genes and CRISPR arrays that suggest multiple encounters with foreign DNA. Presence of genomic exchange traits was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.

Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium

DEFF Research Database (Denmark)

Machado, Henrique; Gram, Lone

2017-01-01

was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.......Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand...... the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur, amino-acid usage, ANI), which allowed us to identify two...

Ground-based eye-safe networkable micro-pulse differential absorption and high spectral resolution lidar for water vapor and aerosol profiling in the lower troposphere

Science.gov (United States)

Repasky, K. S.; Spuler, S.; Hayman, M. M.; Bunn, C. E.

2017-12-01

Atmospheric water vapor is a greenhouse gas that is known to be a significant driver of weather and climate. Several National Research Council (NRC) reports have highlighted the need for improved water vapor measurements that can capture its spatial and temporal variability as a means to improve weather predictions. Researchers at Montana State University (MSU) and the National Center for Atmospheric Research (NCAR) have developed an eye-safe diode laser based micro-pulse differential absorption lidar (MP-DIAL) for water vapor profiling in the lower troposphere. The MP-DIAL is capable of long term unattended operation and is capable of monitoring water vapor in the lower troposphere in most weather conditions. Two MP-DIAL instruments are currently operational and have been deployed at the Front Range Air Pollution and Photochemistry Experiment (FRAPPE), the Plains elevated Convection at Night (PECAN) experiment, the Perdigão experiment, and the Land Atmosphere Feedback Experiment (LAFE). For each of these field experiments, the MP-DIAL was run unattended and provided near-continuous water vapor profiles, including periods of bright daytime clouds, from 300 m above the ground level to 4 km (or the cloud base) with 150 m vertical resolution and 5 minute temporal resolution. Three additional MP-DIAL instruments are currently under construction and will result in a network of five eye-safe MP-DIAL instruments for ground based weather and climate research experiments. Taking advantage of the broad spectral coverage and modularity or the diode based architecture, a high spectral resolution lidar (HSRL) measurement capabilities was added to the second MP-DIAL instrument. The HSRL capabilities will be operational during the deployment at the LAFE field experiment. The instrument architecture will be presented along with examples of data collected during recent field experiments.

High-resolution copy-number variation map reflects human olfactory receptor diversity and evolution.

Directory of Open Access Journals (Sweden)

Yehudit Hasin

2008-11-01

Full Text Available Olfactory receptors (ORs, which are involved in odorant recognition, form the largest mammalian protein superfamily. The genomic content of OR genes is considerably reduced in humans, as reflected by the relatively small repertoire size and the high fraction ( approximately 55% of human pseudogenes. Since several recent low-resolution surveys suggested that OR genomic loci are frequently affected by copy-number variants (CNVs, we hypothesized that CNVs may play an important role in the evolution of the human olfactory repertoire. We used high-resolution oligonucleotide tiling microarrays to detect CNVs across 851 OR gene and pseudogene loci. Examining genomic DNA from 25 individuals with ancestry from three populations, we identified 93 OR gene loci and 151 pseudogene loci affected by CNVs, generating a mosaic of OR dosages across persons. Our data suggest that approximately 50% of the CNVs involve more than one OR, with the largest CNV spanning 11 loci. In contrast to earlier reports, we observe that CNVs are more frequent among OR pseudogenes than among intact genes, presumably due to both selective constraints and CNV formation biases. Furthermore, our results show an enrichment of CNVs among ORs with a close human paralog or lacking a one-to-one ortholog in chimpanzee. Interestingly, among the latter we observed an enrichment in CNV losses over gains, a finding potentially related to the known diminution of the human OR repertoire. Quantitative PCR experiments performed for 122 sampled ORs agreed well with the microarray results and uncovered 23 additional CNVs. Importantly, these experiments allowed us to uncover nine common deletion alleles that affect 15 OR genes and five pseudogenes. Comparison to the chimpanzee reference genome revealed that all of the deletion alleles are human derived, therefore indicating a profound effect of human-specific deletions on the individual OR gene content. Furthermore, these deletion alleles may be used

Methylation-sensitive amplified polymorphism-based genome-wide analysis of cytosine methylation profiles in Nicotiana tabacum cultivars.

Science.gov (United States)

Jiao, J; Wu, J; Lv, Z; Sun, C; Gao, L; Yan, X; Cui, L; Tang, Z; Yan, B; Jia, Y

2015-11-26

This study aimed to investigate cytosine methylation profiles in different tobacco (Nicotiana tabacum) cultivars grown in China. Methylation-sensitive amplified polymorphism was used to analyze genome-wide global methylation profiles in four tobacco cultivars (Yunyan 85, NC89, K326, and Yunyan 87). Amplicons with methylated C motifs were cloned by reamplified polymerase chain reaction, sequenced, and analyzed. The results show that geographical location had a greater effect on methylation patterns in the tobacco genome than did sampling time. Analysis of the CG dinucleotide distribution in methylation-sensitive polymorphic restriction fragments suggested that a CpG dinucleotide cluster-enriched area is a possible site of cytosine methylation in the tobacco genome. The sequence alignments of the Nia1 gene (that encodes nitrate reductase) in Yunyan 87 in different regions indicate that a C-T transition might be responsible for the tobacco phenotype. T-C nucleotide replacement might also be responsible for the tobacco phenotype and may be influenced by geographical location.

Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.

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Abida, Wassim; Armenia, Joshua; Gopalan, Anuradha; Brennan, Ryan; Walsh, Michael; Barron, David; Danila, Daniel; Rathkopf, Dana; Morris, Michael; Slovin, Susan; McLaughlin, Brigit; Curtis, Kristen; Hyman, David M; Durack, Jeremy C; Solomon, Stephen B; Arcila, Maria E; Zehir, Ahmet; Syed, Aijazuddin; Gao, Jianjiong; Chakravarty, Debyani; Vargas, Hebert Alberto; Robson, Mark E; Joseph, Vijai; Offit, Kenneth; Donoghue, Mark T A; Abeshouse, Adam A; Kundra, Ritika; Heins, Zachary J; Penson, Alexander V; Harris, Christopher; Taylor, Barry S; Ladanyi, Marc; Mandelker, Diana; Zhang, Liying; Reuter, Victor E; Kantoff, Philip W; Solit, David B; Berger, Michael F; Sawyers, Charles L; Schultz, Nikolaus; Scher, Howard I

2017-07-01

A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in the disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic non-castrate, and metastatic castration-resistant prostate cancer (CRPC). Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was employed to identify single nucleotide variations, small insertions and deletions, copy number alterations and structural rearrangements in over 300 cancer-related genes in tumors and matched normal blood. We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair (DDR), PI3K, and MAP kinase pathways. 27% of patients harbored a germline or a somatic alteration in a DDR gene that may predict for response to PARP inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, while ATM alterations were specifically enriched in CRPC. Through genomic profiling of prostate tumors representing the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis and castration-resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.

Managing the genomic revolution in cancer diagnostics.

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Nguyen, Doreen; Gocke, Christopher D

2017-08-01

Molecular tumor profiling is now a routine part of patient care, revealing targetable genomic alterations and molecularly distinct tumor subtypes with therapeutic and prognostic implications. The widespread adoption of next-generation sequencing technologies has greatly facilitated clinical implementation of genomic data and opened the door for high-throughput multigene-targeted sequencing. Herein, we discuss the variability of cancer genetic profiling currently offered by clinical laboratories, the challenges of applying rapidly evolving medical knowledge to individual patients, and the need for more standardized population-based molecular profiling.

Comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane between normal and preeclampsia pregnancies with high-resolution mass spectrometry.

Directory of Open Access Journals (Sweden)

Fuqiang Wang

Full Text Available Preeclampsia is a serious complication of pregnancy, which affects 2-8% of all pregnancies and is one of the leading causes of maternal and perinatal mortality and morbidity worldwide. To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used high-resolution LC-MS/MS technologies to construct a comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane in normal and preeclamptic pregnancies. A total of 1027 N-glyco- and 2094 phospho- sites were detected in human placental plasma membrane, and 5 N-glyco- and 38 phospho- proteins, respectively, with differentially expression were definitively identified between control and preeclamptic placental plasma membrane. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes occurring during pathological changes of preeclamptic placental plasma membrane.

Adult high-grade B-cell lymphoma with Burkitt lymphoma signature: genomic features and potential therapeutic targets.

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Bouska, Alyssa; Bi, Chengfeng; Lone, Waseem; Zhang, Weiwei; Kedwaii, Ambreen; Heavican, Tayla; Lachel, Cynthia M; Yu, Jiayu; Ferro, Roberto; Eldorghamy, Nanees; Greiner, Timothy C; Vose, Julie; Weisenburger, Dennis D; Gascoyne, Randy D; Rosenwald, Andreas; Ott, German; Campo, Elias; Rimsza, Lisa M; Jaffe, Elaine S; Braziel, Rita M; Siebert, Reiner; Miles, Rodney R; Dave, Sandeep; Reddy, Anupama; Delabie, Jan; Staudt, Louis M; Song, Joo Y; McKeithan, Timothy W; Fu, Kai; Green, Michael; Chan, Wing C; Iqbal, Javeed

2017-10-19

The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes. Mutations in genes promoting the tonic B-cell receptor (BCR)→PI3K pathway ( TCF3 and ID3 ) did not differ by age, whereas effectors of chronic BCR→NF-κB signaling were associated with adult-mBL. A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation profile similar to mBL. These double-hit lymphomas may have arisen from a tumor precursor that acquired both BCL2 and MYC translocations and/or KMT2D ( MLL2 ) mutation. Gain/amplification of MIR17HG and its paralogue loci was observed in 50% of adult-mBL. In vitro studies suggested miR-17∼92 's role in constitutive activation of BCR signaling and sensitivity to ibrutinib. Overall integrative analysis identified an interrelated gene network affected by copy number and mutation, leading to disruption of the p53 pathway and the BCR→PI3K or NF-κB activation, which can be further exploited in vivo by small-molecule inhibitors for effective therapy in adult-mBL.

High-resolution phenotypic profiling of natural products-induced effects on the single-cell level

KAUST Repository

Kremb, Stephan Georg

2017-03-15

Natural products (NPs) are highly evolved molecules making them a valuable resource for new therapeutics. Here we demonstrate the usefulness of broad-spectrum phenotypic profiling of NP-induced perturbations on single cells with imaging-based High-Content Screening to inform on physiology, mechanisms-of-actions, and multi-level toxicity. Our technology platform aims at broad applicability using a comprehensive marker panel with standardized settings streamlined towards an easy implementation in laboratories dedicated to natural products research.

Defining the Core Genome of Salmonella enterica Serovar Typhimurium for Genomic Surveillance and Epidemiological Typing

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Fu, Songzhe; Octavia, Sophie; Tanaka, Mark M.; Sintchenko, Vitali

2015-01-01

Salmonella enterica serovar Typhimurium is the most common Salmonella serovar causing foodborne infections in Australia and many other countries. Twenty-one S. Typhimurium strains from Salmonella reference collection A (SARA) were analyzed using Illumina high-throughput genome sequencing. Single nucleotide polymorphisms (SNPs) in 21 SARA strains ranged from 46 to 11,916 SNPs, with an average of 1,577 SNPs per strain. Together with 47 strains selected from publicly available S. Typhimurium genomes, the S. Typhimurium core genes (STCG) were determined. The STCG consist of 3,846 genes, a set that is much larger than that of the 2,882 Salmonella core genes (SCG) found previously. The STCG together with 1,576 core intergenic regions (IGRs) were defined as the S. Typhimurium core genome. Using 93 S. Typhimurium genomes from 13 epidemiologically confirmed community outbreaks, we demonstrated that typing based on the S. Typhimurium core genome (STCG plus core IGRs) provides superior resolution and higher discriminatory power than that based on SCG for outbreak investigation and molecular epidemiology of S. Typhimurium. STCG and STCG plus core IGR typing achieved 100% separation of all outbreaks compared to that of SCG typing, which failed to separate isolates from two outbreaks from background isolates. Defining the S. Typhimurium core genome allows standardization of genes/regions to be used for high-resolution epidemiological typing and genomic surveillance of S. Typhimurium. PMID:26019201

Rapid and inexpensive body fluid identification by RNA profiling-based multiplex High Resolution Melt (HRM) analysis.

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Hanson, Erin K; Ballantyne, Jack

2013-01-01

Positive identification of the nature of biological material present on evidentiary items can be crucial for understanding the circumstances surrounding a crime. However, traditional protein-based methods do not permit the identification of all body fluids and tissues, and thus molecular based strategies for the conclusive identification of all forensically relevant biological fluids and tissues need to be developed. Messenger RNA (mRNA) profiling is an example of such a molecular-based approach. Current mRNA body fluid identification assays involve capillary electrophoresis (CE) or quantitative RT-PCR (qRT-PCR) platforms, each with its own limitations. Both platforms require the use of expensive fluorescently labeled primers or probes. CE-based assays require separate amplification and detection steps thus increasing the analysis time. For qRT-PCR assays, only 3-4 markers can be included in a single reaction since each requires a different fluorescent dye. To simplify mRNA profiling assays, and reduce the time and cost of analysis, we have developed single- and multiplex body fluid High Resolution Melt (HRM) assays for the identification of common forensically relevant biological fluids and tissues. The incorporated biomarkers include IL19 (vaginal secretions), IL1F7 (skin), ALAS2 (blood), MMP10 (menstrual blood), HTN3 (saliva) and TGM4 (semen).  The HRM assays require only unlabeled PCR primers and a single saturating intercalating fluorescent dye (Eva Green). Each body-fluid-specific marker can easily be identified by the presence of a distinct melt peak. Usually, HRM assays are used to detect variants or isoforms for a single gene target. However, we have uniquely developed duplex and triplex HRM assays to permit the simultaneous detection of multiple targets per reaction. Here we describe the development and initial performance evaluation of the developed HRM assays. The results demonstrate the potential use of HRM assays for rapid, and relatively inexpensive

OTR profile measurement of a LINAC electron beam with portable ultra high-speed camera

International Nuclear Information System (INIS)

Mogi, T.; Nisiyama, S.; Tomioka, S.; Enoto, T.

2004-01-01

We have studied on and developed a portable ultra high-speed camera, and so applied to measurement of a LINAC electron beam. We measured spatial OTR profiles of a LINAC electron beam using this camera with temporal resolution 80ns. (author)

Te and ne profiles on JFT-2M plasma with the highest spatial resolution TV Thomson scattering system

International Nuclear Information System (INIS)

Yamauchi, T.

1993-01-01

A high spatial resolution TV Thomson scattering system was constructed on JFT-2M tokamak. This system is similar to those used at PBX-M and TFTR. These systems are providing complete profiles of Te and ne at a single time during a plasma discharge. The characteristics of JFT-2M TVTS are as follows: 1. Measured points are composed of not only 81 points for the scattered light and plasma light, whose time difference is 2 ms, but also 10 points for plasma light measured at the same time with scattered light. 2. Spatial resolution is 0.86 cm, which is higher than any other Thomson scattering system. 3. Sensitivity of detector composed of image intensifier tubes and CCD is as high as that of photomultiplier tube. Te and ne profiles have been measured over one year on JFT-2M. The line-averaged electron density measured was in the region of 5x10 12 cm -3 - 7x10 13 cm -3 and the measured electron temperature was in the region of 50 eV -1.2 keV. (author) 7 refs., 7 figs., 1 tab

Molecular profile and copy number analysis of sporadic colorectal cancer in Taiwan

Directory of Open Access Journals (Sweden)

Li Ling-Hui

2011-06-01

Full Text Available Abstract Background Colorectal cancer (CRC is a major health concern worldwide, and recently becomes the most common cancer in Asia. The case collection of this study is one of the largest sets of CRC in Asia, and serves as representative data for investigating genomic differences between ethnic populations. We took comprehensive and high-resolution approaches to compare the clinicopathologic and genomic profiles of microsatellite instability (MSI vs. microsatellite stability (MSS in Taiwanese sporadic CRCs. Methods 1,173 CRC tumors were collected from the Taiwan population, and sequencing-based microsatellite typing assay was used to determine MSI and MSS. Genome-wide SNP array was used to detect CN alterations in 16 MSI-H and 13 MSS CRCs and CN variations in 424 general controls. Gene expression array was used to evaluate the effects of CN alterations, and quantitative PCR methods were used to replicate the findings in independent clinical samples. Results These 1,173 CRC tumors can be classified into 75 high-frequency MSI (MSI-H (6.4%, 96 low-frequency MSI (8.2% and 1,002 MSS (85.4%. Of the 75 MSI-H tumors, 22 had a BRAF mutation and 51 showed MLH1 promoter hypermethylation. There were distinctive differences in the extent of CN alterations between CRC MSS and MSI-H subtypes (300 Mb vs. 42 Mb per genome, p-value Conclusions Sporadic CRCs with MSI-H displayed distinguishable clinicopathologic features, which differ from those of MSS. Genomic profiling of the two types of sporadic CRCs revealed significant differences in the extent and distribution of CN alterations in the cancer genome. More than half of expressed genes showing CN differences can directly contribute to their expressional diversities, and the biological functions of the genes associated with CN changes in sporadic CRCs warrant further investigation to establish their possible clinical implications.

Compressive sensing for high resolution profiles with enhanced Doppler performance

NARCIS (Netherlands)

Anitori, L.; Hoogeboom, P.; Chevalier, F. Le; Otten, M.P.G.

2012-01-01

In this paper we demonstrate how Compressive Sensing (CS) can be used in pulse-Doppler radars to improve the Doppler performance while preserving range resolution. We investigate here two types of stepped frequency waveforms, the coherent frequency bursts and successive frequency ramps, which can be

Berkeley High-Resolution Ball

International Nuclear Information System (INIS)

Diamond, R.M.

1984-10-01

Criteria for a high-resolution γ-ray system are discussed. Desirable properties are high resolution, good response function, and moderate solid angle so as to achieve not only double- but triple-coincidences with good statistics. The Berkeley High-Resolution Ball involved the first use of bismuth germanate (BGO) for anti-Compton shield for Ge detectors. The resulting compact shield permitted rather close packing of 21 detectors around a target. In addition, a small central BGO ball gives the total γ-ray energy and multiplicity, as well as the angular pattern of the γ rays. The 21-detector array is nearly complete, and the central ball has been designed, but not yet constructed. First results taken with 9 detector modules are shown for the nucleus 156 Er. The complex decay scheme indicates a transition from collective rotation (prolate shape) to single- particle states (possibly oblate) near spin 30 h, and has other interesting features

Whole-genome shotgun optical mapping of rhodospirillumrubrum

Energy Technology Data Exchange (ETDEWEB)

Reslewic, Susan; Zhou, Shiguo; Place, Mike; Zhang, Yaoping; Briska, Adam; Goldstein, Steve; Churas, Chris; Runnheim, Rod; Forrest,Dan; Lim, Alex; Lapidus, Alla; Han, Cliff S.; Roberts, Gary P.; Schwartz,David C.

2004-07-01

Rhodospirillum rubrum is a phototrophic purple non-sulfur bacterium known for its unique and well-studied nitrogen fixation and carbon monoxide oxidation systems, and as a source of hydrogen and biodegradable plastics production. To better understand this organism and to facilitate assembly of its sequence, three whole-genome restriction maps (Xba I, Nhe I, and Hind III) of R. rubrum strain ATCC 11170 were created by optical mapping. Optical mapping is a system for creating whole-genome ordered restriction maps from randomly sheared genomic DNA molecules extracted directly from cells. During the sequence finishing process, all three optical maps confirmed a putative error in sequence assembly, while the Hind III map acted as a scaffold for high resolution alignment with sequence contigs spanning the whole genome. In addition to highlighting optical mapping's role in the assembly and validation of genome sequence, our work underscores the unique niche in resolution occupied by the optical mapping system. With a resolution ranging from 6.5 kb (previously published) to 45 kb (reported here), optical mapping advances a ''molecular cytogenetics'' approach to solving problems in genomic analysis.

The Front Line of Genomic Translation

International Nuclear Information System (INIS)

O'Neill, C. S.; McBride, C. M.; Koehly, L. M.; Bryan, A. D.; Wideroff, L.

2012-01-01

Cancer prevention, detection, and treatment represent the front line of genomic translation. Increasingly, new genomic knowledge is being used to inform personalized cancer prevention recommendations and treatment [1-3]. Genomic applications proposed and realized span the full cancer continuum, from cancer prevention and early detection vis a vis genomic risk profiles to motivate behavioral risk reduction and adherence [4] to screening and prophylactic prevention recommendations for high-risk families [5-7], to enhancing cancer survivorship by using genomic tumor profiles to inform treatment decisions and targeted cancer therapies [8, 9]. Yet the utility for many of these applications is as yet unclear and will be influenced heavily by the public’s, patients’, and health care providers’ responses and in numerous other factors, such as health care delivery models [3]. The contributors to this special issue consider various target groups’ responses and contextual factors. To reflect the cancer continuum, the special issue is divided into three broad, overlapping themes-primary prevention, high risk families and family communication and clinical translation.

Advancing understanding of the fluvial export of organic matter through high-resolution profiling of dissolved organic carbon.

Science.gov (United States)

Waldron, S.; Drew, S.; Gilvear, D.; Murray, H.; Heal, K.

2012-04-01

Quantifying the natural variation (complexity) of a system remains an enduring scientific challenge in better understanding controls on surface water quality. This characterisation is needed in order to reveal controlling processes, such as dilution, and also to identify unusual load profiles. In trying to capture that natural variation we still rely largely on concentration time series (and associated export budgets) generated from manual spot sampling, or from samples collected by autosamplers - approaches which are unlikely to provide the high temporal resolution of parameter concentration required. Now however, advances in sensor technology are helping us address this challenge. Here we present detailed dissolved organic carbon (DOC) export profiles from a small upland river (9.4 km sq.), generated since June 2011 by semi-continuous logging of UV-vis absorption (200-750 nm, every 2.5 nm) every 30 minutes. Observed increases in the concentration of the DOC, [DOC], in freshwaters have prompted significant research to understand the cause and consequences of increased export: higher levels of DOC require additional water purification of potable sources; increased aquatic export may represent a reduction in terrestrial C-soil sequestration; changes in light penetration can affect the heterotrophic / autotrophic balance in surface waters and this has consequences for the food web structure; increased aquatic export may also result in increased carbon dioxide evasion. Additionally, C export is often linked to nutrient export: we have observed statistically significant stoichiometric relationships between DOC and soluble reactive phosphorus (SRP) concentrations, thus understanding better this parameters offers insight into export of other nutrient and the source of material from which these dissolved compounds are produced; this may be particulate. Our Scottish study site is interesting because there are multiple processes that can contribute to DOC and other nutrient

Effective Normalization for Copy Number Variation Detection from Whole Genome Sequencing

NARCIS (Netherlands)

Janevski, A.; Varadan, V.; Kamalakaran, S.; Banerjee, N.; Dimitrova, D.

2012-01-01

Background Whole genome sequencing enables a high resolution view ofthe human genome and provides unique insights into genome structureat an unprecedented scale. There have been a number of tools to infer copy number variation in the genome. These tools while validatedalso include a number of

High Spatio-Temporal Resolution Bathymetry Estimation and Morphology

Science.gov (United States)

Bergsma, E. W. J.; Conley, D. C.; Davidson, M. A.; O'Hare, T. J.

2015-12-01

In recent years, bathymetry estimates using video images have become increasingly accurate. With the cBathy code (Holman et al., 2013) fully operational, bathymetry results with 0.5 metres accuracy have been regularly obtained at Duck, USA. cBathy is based on observations of the dominant frequencies and wavelengths of surface wave motions and estimates the depth (and hence allows inference of bathymetry profiles) based on linear wave theory. Despite the good performance at Duck, large discrepancies were found related to tidal elevation and camera height (Bergsma et al., 2014) and on the camera boundaries. A tide dependent floating pixel and camera boundary solution have been proposed to overcome these issues (Bergsma et al., under review). The video-data collection is set estimate depths hourly on a grid with resolution in the order of 10x25 meters. Here, the application of the cBathy at Porthtowan in the South-West of England is presented. Hourly depth estimates are combined and analysed over a period of 1.5 years (2013-2014). In this work the focus is on the sub-tidal region, where the best cBathy results are achieved. The morphology of the sub-tidal bar is tracked with high spatio-temporal resolution on short and longer time scales. Furthermore, the impact of the storm and reset (sudden and large changes in bathymetry) of the sub-tidal area is clearly captured with the depth estimations. This application shows that the high spatio-temporal resolution of cBathy makes it a powerful tool for coastal research and coastal zone management.

In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features.

Science.gov (United States)

Ding, Yiliang; Tang, Yin; Kwok, Chun Kit; Zhang, Yu; Bevilacqua, Philip C; Assmann, Sarah M

2014-01-30

RNA structure has critical roles in processes ranging from ligand sensing to the regulation of translation, polyadenylation and splicing. However, a lack of genome-wide in vivo RNA structural data has limited our understanding of how RNA structure regulates gene expression in living cells. Here we present a high-throughput, genome-wide in vivo RNA structure probing method, structure-seq, in which dimethyl sulphate methylation of unprotected adenines and cytosines is identified by next-generation sequencing. Application of this method to Arabidopsis thaliana seedlings yielded the first in vivo genome-wide RNA structure map at nucleotide resolution for any organism, with quantitative structural information across more than 10,000 transcripts. Our analysis reveals a three-nucleotide periodic repeat pattern in the structure of coding regions, as well as a less-structured region immediately upstream of the start codon, and shows that these features are strongly correlated with translation efficiency. We also find patterns of strong and weak secondary structure at sites of alternative polyadenylation, as well as strong secondary structure at 5' splice sites that correlates with unspliced events. Notably, in vivo structures of messenger RNAs annotated for stress responses are poorly predicted in silico, whereas mRNA structures of genes related to cell function maintenance are well predicted. Global comparison of several structural features between these two categories shows that the mRNAs associated with stress responses tend to have more single-strandedness, longer maximal loop length and higher free energy per nucleotide, features that may allow these RNAs to undergo conformational changes in response to environmental conditions. Structure-seq allows the RNA structurome and its biological roles to be interrogated on a genome-wide scale and should be applicable to any organism.

Linearized inversion frameworks toward high-resolution seismic imaging

KAUST Repository

Aldawood, Ali

2016-09-01

internally multiply scattered seismic waves to obtain highly resolved images delineating vertical faults that are otherwise not easily imaged by primaries. Seismic interferometry is conventionally based on the cross-correlation and convolution of seismic traces to transform seismic data from one acquisition geometry to another. The conventional interferometric transformation yields virtual data that suffers from low temporal resolution, wavelet distortion, and correlation/convolution artifacts. I therefore incorporate a least-squares datuming technique to interferometrically transform vertical-seismic-profile surface-related multiples to surface-seismic-profile primaries. This yields redatumed data with high temporal resolution and less artifacts, which are subsequently imaged to obtain highly resolved subsurface images. Tests on synthetic examples demonstrate the efficiency of the proposed techniques, yielding highly resolved migrated sections compared with images obtained by imaging conventionally redatumed data. I further advance the recently developed cost-effective Generalized Interferometric Multiple Imaging procedure, which aims to not only image first but also higher-order multiples as well. I formulate this procedure as a linearized inversion framework and solve it as a least-squares problem. Tests of the least-squares Generalized Interferometric Multiple imaging framework on synthetic datasets and demonstrate that it could provide highly resolved migrated images and delineate vertical fault planes compared with the standard procedure. The results support the assertion that this linearized inversion framework can illuminate subsurface zones that are mainly illuminated by internally scattered energy.

Versatile Gene-Specific Sequence Tags for Arabidopsis Functional Genomics: Transcript Profiling and Reverse Genetics Applications

Science.gov (United States)

Hilson, Pierre; Allemeersch, Joke; Altmann, Thomas; Aubourg, Sébastien; Avon, Alexandra; Beynon, Jim; Bhalerao, Rishikesh P.; Bitton, Frédérique; Caboche, Michel; Cannoot, Bernard; Chardakov, Vasil; Cognet-Holliger, Cécile; Colot, Vincent; Crowe, Mark; Darimont, Caroline; Durinck, Steffen; Eickhoff, Holger; de Longevialle, Andéol Falcon; Farmer, Edward E.; Grant, Murray; Kuiper, Martin T.R.; Lehrach, Hans; Léon, Céline; Leyva, Antonio; Lundeberg, Joakim; Lurin, Claire; Moreau, Yves; Nietfeld, Wilfried; Paz-Ares, Javier; Reymond, Philippe; Rouzé, Pierre; Sandberg, Goran; Segura, Maria Dolores; Serizet, Carine; Tabrett, Alexandra; Taconnat, Ludivine; Thareau, Vincent; Van Hummelen, Paul; Vercruysse, Steven; Vuylsteke, Marnik; Weingartner, Magdalena; Weisbeek, Peter J.; Wirta, Valtteri; Wittink, Floyd R.A.; Zabeau, Marc; Small, Ian

2004-01-01

Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics. PMID:15489341

High-Resolution PET Detector. Final report

International Nuclear Information System (INIS)

Karp, Joel

2014-01-01

The objective of this project was to develop an understanding of the limits of performance for a high resolution PET detector using an approach based on continuous scintillation crystals rather than pixelated crystals. The overall goal was to design a high-resolution detector, which requires both high spatial resolution and high sensitivity for 511 keV gammas. Continuous scintillation detectors (Anger cameras) have been used extensively for both single-photon and PET scanners, however, these instruments were based on NaI(Tl) scintillators using relatively large, individual photo-multipliers. In this project we investigated the potential of this type of detector technology to achieve higher spatial resolution through the use of improved scintillator materials and photo-sensors, and modification of the detector surface to optimize the light response function.We achieved an average spatial resolution of 3-mm for a 25-mm thick, LYSO continuous detector using a maximum likelihood position algorithm and shallow slots cut into the entrance surface

AirCore-HR: a high-resolution column sampling to enhance the vertical description of CH4 and CO2

Directory of Open Access Journals (Sweden)

O. Membrive

2017-06-01

Full Text Available An original and innovative sampling system called AirCore was presented by NOAA in 2010 (Karion et al., 2010. It consists of a long (>  100 m and narrow (<  1 cm stainless steel tube that can retain a profile of atmospheric air. The captured air sample has then to be analyzed with a gas analyzer for trace mole fraction. In this study, we introduce a new AirCore aiming to improve resolution along the vertical with the objectives to (i better capture the vertical distribution of CO2 and CH4, (ii provide a tool to compare AirCores and validate the estimated vertical resolution achieved by AirCores. This (high-resolution AirCore-HR consists of a 300 m tube, combining 200 m of 0.125 in. (3.175 mm tube and a 100 m of 0.25 in. (6.35 mm tube. This new configuration allows us to achieve a vertical resolution of 300 m up to 15 km and better than 500 m up to 22 km (if analysis of the retained sample is performed within 3 h. The AirCore-HR was flown for the first time during the annual StratoScience campaign from CNES in August 2014 from Timmins (Ontario, Canada. High-resolution vertical profiles of CO2 and CH4 up to 25 km were successfully retrieved. These profiles revealed well-defined transport structures in the troposphere (also seen in CAMS-ECMWF high-resolution forecasts of CO2 and CH4 profiles and captured the decrease of CO2 and CH4 in the stratosphere. The multi-instrument gondola also carried two other low-resolution AirCore-GUF that allowed us to perform direct comparisons and study the underlying processing method used to convert the sample of air to greenhouse gases vertical profiles. In particular, degrading the AirCore-HR derived profiles to the low resolution of AirCore-GUF yields an excellent match between both sets of CH4 profiles and shows a good consistency in terms of vertical structures. This fully validates the theoretical vertical resolution achievable by AirCores. Concerning CO2 although a

Epigenomics of Total Acute Sleep Deprivation in Relation to Genome-Wide DNA Methylation Profiles and RNA Expression.

Science.gov (United States)

Nilsson, Emil K; Boström, Adrian E; Mwinyi, Jessica; Schiöth, Helgi B

2016-06-01

Despite an established link between sleep deprivation and epigenetic processes in humans, it remains unclear to what extent sleep deprivation modulates DNA methylation. We performed a within-subject randomized blinded study with 16 healthy subjects to examine the effect of one night of total sleep deprivation (TSD) on the genome-wide methylation profile in blood compared with that in normal sleep. Genome-wide differences in methylation between both conditions were assessed by applying a paired regression model that corrected for monocyte subpopulations. In addition, the correlations between the methylation of genes detected to be modulated by TSD and gene expression were examined in a separate, publicly available cohort of 10 healthy male donors (E-GEOD-49065). Sleep deprivation significantly affected the DNA methylation profile both independently and in dependency of shifts in monocyte composition. Our study detected differential methylation of 269 probes. Notably, one CpG site was located 69 bp upstream of ING5, which has been shown to be differentially expressed after sleep deprivation. Gene set enrichment analysis detected the Notch and Wnt signaling pathways to be enriched among the differentially methylated genes. These results provide evidence that total acute sleep deprivation alters the methylation profile in healthy human subjects. This is, to our knowledge, the first study that systematically investigated the impact of total acute sleep deprivation on genome-wide DNA methylation profiles in blood and related the epigenomic findings to the expression data.

Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC and its application for DNA methylation analysis

Directory of Open Access Journals (Sweden)

Ottaviani Diego

2008-05-01

Full Text Available Abstract Background The major histocompatibility complex (MHC is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome. Methods To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP, methylated DNA immunoprecipitation (MeDIP, array comparative genomic hybridization (aCGH and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls. Results Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs. Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation. Conclusion A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.

BarleyBase—an expression profiling database for plant genomics

Science.gov (United States)

Shen, Lishuang; Gong, Jian; Caldo, Rico A.; Nettleton, Dan; Cook, Dianne; Wise, Roger P.; Dickerson, Julie A.

2005-01-01

BarleyBase (BB) (www.barleybase.org) is an online database for plant microarrays with integrated tools for data visualization and statistical analysis. BB houses raw and normalized expression data from the two publicly available Affymetrix genome arrays, Barley1 and Arabidopsis ATH1 with plans to include the new Affymetrix 61K wheat, maize, soybean and rice arrays, as they become available. BB contains a broad set of query and display options at all data levels, ranging from experiments to individual hybridizations to probe sets down to individual probes. Users can perform cross-experiment queries on probe sets based on observed expression profiles and/or based on known biological information. Probe set queries are integrated with visualization and analysis tools such as the R statistical toolbox, data filters and a large variety of plot types. Controlled vocabularies for gene and plant ontologies, as well as interconnecting links to physical or genetic map and other genomic data in PlantGDB, Gramene and GrainGenes, allow users to perform EST alignments and gene function prediction using Barley1 exemplar sequences, thus, enhancing cross-species comparison. PMID:15608273

BioNano genome mapping of individual chromosomes supports physical mapping and sequence assembly in complex plant genomes.

Science.gov (United States)

Staňková, Helena; Hastie, Alex R; Chan, Saki; Vrána, Jan; Tulpová, Zuzana; Kubaláková, Marie; Visendi, Paul; Hayashi, Satomi; Luo, Mingcheng; Batley, Jacqueline; Edwards, David; Doležel, Jaroslav; Šimková, Hana

2016-07-01

The assembly of a reference genome sequence of bread wheat is challenging due to its specific features such as the genome size of 17 Gbp, polyploid nature and prevalence of repetitive sequences. BAC-by-BAC sequencing based on chromosomal physical maps, adopted by the International Wheat Genome Sequencing Consortium as the key strategy, reduces problems caused by the genome complexity and polyploidy, but the repeat content still hampers the sequence assembly. Availability of a high-resolution genomic map to guide sequence scaffolding and validate physical map and sequence assemblies would be highly beneficial to obtaining an accurate and complete genome sequence. Here, we chose the short arm of chromosome 7D (7DS) as a model to demonstrate for the first time that it is possible to couple chromosome flow sorting with genome mapping in nanochannel arrays and create a de novo genome map of a wheat chromosome. We constructed a high-resolution chromosome map composed of 371 contigs with an N50 of 1.3 Mb. Long DNA molecules achieved by our approach facilitated chromosome-scale analysis of repetitive sequences and revealed a ~800-kb array of tandem repeats intractable to current DNA sequencing technologies. Anchoring 7DS sequence assemblies obtained by clone-by-clone sequencing to the 7DS genome map provided a valuable tool to improve the BAC-contig physical map and validate sequence assembly on a chromosome-arm scale. Our results indicate that creating genome maps for the whole wheat genome in a chromosome-by-chromosome manner is feasible and that they will be an affordable tool to support the production of improved pseudomolecules. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Genomic outlier profile analysis: mixture models, null hypotheses, and nonparametric estimation.

Science.gov (United States)

Ghosh, Debashis; Chinnaiyan, Arul M

2009-01-01

In most analyses of large-scale genomic data sets, differential expression analysis is typically assessed by testing for differences in the mean of the distributions between 2 groups. A recent finding by Tomlins and others (2005) is of a different type of pattern of differential expression in which a fraction of samples in one group have overexpression relative to samples in the other group. In this work, we describe a general mixture model framework for the assessment of this type of expression, called outlier profile analysis. We start by considering the single-gene situation and establishing results on identifiability. We propose 2 nonparametric estimation procedures that have natural links to familiar multiple testing procedures. We then develop multivariate extensions of this methodology to handle genome-wide measurements. The proposed methodologies are compared using simulation studies as well as data from a prostate cancer gene expression study.

Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in Wilms tumor.

Science.gov (United States)

Williams, Richard D; Al-Saadi, Reem; Natrajan, Rachael; Mackay, Alan; Chagtai, Tasnim; Little, Suzanne; Hing, Sandra N; Fenwick, Kerry; Ashworth, Alan; Grundy, Paul; Anderson, James R; Dome, Jeffrey S; Perlman, Elizabeth J; Jones, Chris; Pritchard-Jones, Kathy

2011-12-01

Anaplasia in Wilms tumor, a distinctive histology characterized by abnormal mitoses, is associated with poor patient outcome. While anaplastic tumors frequently harbour TP53 mutations, little is otherwise known about their molecular biology. We have used array comparative genomic hybridization (aCGH) and cDNA microarray expression profiling to compare anaplastic and favorable histology Wilms tumors to determine their common and differentiating features. In addition to changes on 17p, consistent with TP53 deletion, recurrent anaplasia-specific genomic loss and under-expression were noted in several other regions, most strikingly 4q and 14q. Further aberrations, including gain of 1q and loss of 16q were common to both histologies. Focal gain of MYCN, initially detected by high resolution aCGH profiling in 6/61 anaplastic samples, was confirmed in a significant proportion of both tumor types by a genomic quantitative PCR survey of over 400 tumors. Overall, these results are consistent with a model where anaplasia, rather than forming an entirely distinct molecular entity, arises from the general continuum of Wilms tumor by the acquisition of additional genomic changes at multiple loci. Copyright © 2011 Wiley Periodicals, Inc.

Demonstration of a diode-laser-based high spectral resolution lidar (HSRL) for quantitative profiling of clouds and aerosols.

Science.gov (United States)

Hayman, Matthew; Spuler, Scott

2017-11-27

We present a demonstration of a diode-laser-based high spectral resolution lidar. It is capable of performing calibrated retrievals of aerosol and cloud optical properties at a 150 m range resolution with less than 1 minute integration time over an approximate range of 12 km during day and night. This instrument operates at 780 nm, a wavelength that is well established for reliable semiconductor lasers and detectors, and was chosen because it corresponds to the D2 rubidium absorption line. A heated vapor reference cell of isotopic rubidium 87 is used as an effective and reliable aerosol signal blocking filter in the instrument. In principle, the diode-laser-based high spectral resolution lidar can be made cost competitive with elastic backscatter lidar systems, yet delivers a significant improvement in data quality through direct retrieval of quantitative optical properties of clouds and aerosols.

High resolution sequence stratigraphy in China

International Nuclear Information System (INIS)

Zhang Shangfeng; Zhang Changmin; Yin Yanshi; Yin Taiju

2008-01-01

Since high resolution sequence stratigraphy was introduced into China by DENG Hong-wen in 1995, it has been experienced two development stages in China which are the beginning stage of theory research and development of theory research and application, and the stage of theoretical maturity and widely application that is going into. It is proved by practices that high resolution sequence stratigraphy plays more and more important roles in the exploration and development of oil and gas in Chinese continental oil-bearing basin and the research field spreads to the exploration of coal mine, uranium mine and other strata deposits. However, the theory of high resolution sequence stratigraphy still has some shortages, it should be improved in many aspects. The authors point out that high resolution sequence stratigraphy should be characterized quantitatively and modelized by computer techniques. (authors)

Developing High-resolution Soil Database for Regional Crop Modeling in East Africa

Science.gov (United States)

Han, E.; Ines, A. V. M.

2014-12-01

The most readily available soil data for regional crop modeling in Africa is the World Inventory of Soil Emission potentials (WISE) dataset, which has 1125 soil profiles for the world, but does not extensively cover countries Ethiopia, Kenya, Uganda and Tanzania in East Africa. Another dataset available is the HC27 (Harvest Choice by IFPRI) in a gridded format (10km) but composed of generic soil profiles based on only three criteria (texture, rooting depth, and organic carbon content). In this paper, we present a development and application of a high-resolution (1km), gridded soil database for regional crop modeling in East Africa. Basic soil information is extracted from Africa Soil Information Service (AfSIS), which provides essential soil properties (bulk density, soil organic carbon, soil PH and percentages of sand, silt and clay) for 6 different standardized soil layers (5, 15, 30, 60, 100 and 200 cm) in 1km resolution. Soil hydraulic properties (e.g., field capacity and wilting point) are derived from the AfSIS soil dataset using well-proven pedo-transfer functions and are customized for DSSAT-CSM soil data requirements. The crop model is used to evaluate crop yield forecasts using the new high resolution soil database and compared with WISE and HC27. In this paper we will present also the results of DSSAT loosely coupled with a hydrologic model (VIC) to assimilate root-zone soil moisture. Creating a grid-based soil database, which provides a consistent soil input for two different models (DSSAT and VIC) is a critical part of this work. The created soil database is expected to contribute to future applications of DSSAT crop simulation in East Africa where food security is highly vulnerable.

Vertical profiles of BC direct radiative effect over Italy: high vertical resolution data and atmospheric feedbacks

Science.gov (United States)

Močnik, Griša; Ferrero, Luca; Castelli, Mariapina; Ferrini, Barbara S.; Moscatelli, Marco; Grazia Perrone, Maria; Sangiorgi, Giorgia; Rovelli, Grazia; D'Angelo, Luca; Moroni, Beatrice; Scardazza, Francesco; Bolzacchini, Ezio; Petitta, Marcello; Cappelletti, David

2016-04-01

Black carbon (BC), and its vertical distribution, affects the climate. Global measurements of BC vertical profiles are lacking to support climate change research. To fill this gap, a campaign was conducted over three Italian basin valleys, Terni Valley (Appennines), Po Valley and Passiria Valley (Alps), to characterize the impact of BC on the radiative budget under similar orographic conditions. 120 vertical profiles were measured in winter 2010. The BC vertical profiles, together with aerosol size distribution, aerosol chemistry and meteorological parameters, have been determined using a tethered balloon-based platform equipped with: a micro-Aethalometer AE51 (Magee Scientific), a 1.107 Grimm OPC (0.25-32 μm, 31 size classes), a cascade impactor (Siuotas SKC), and a meteorological station (LSI-Lastem). The aerosol chemical composition was determined from collected PM2.5 samples. The aerosol absorption along the vertical profiles was measured and optical properties calculated using the Mie theory applied to the aerosol size distribution. The aerosol optical properties were validated with AERONET data and then used as inputs to the radiative transfer model libRadtran. Vertical profiles of the aerosol direct radiative effect, the related atmospheric absorption and the heating rate were calculated. Vertical profile measurements revealed some common behaviors over the studied basin valleys. From below the mixing height to above it, a marked concentration drop was found for both BC (from -48.4±5.3% up to -69.1±5.5%) and aerosol number concentration (from -23.9±4.3% up to -46.5±7.3%). These features reflected on the optical properties of the aerosol. Absorption and scattering coefficients decreased from below the MH to above it (babs from -47.6±2.5% up to -71.3±3.0% and bsca from -23.5±0.8% up to -61.2±3.1%, respectively). Consequently, the Single Scattering Albedo increased above the MH (from +4.9±2.2% to +7.4±1.0%). The highest aerosol absorption was

Whole-genome shotgun optical mapping of Rhodospirillum rubrum

Energy Technology Data Exchange (ETDEWEB)

Reslewic, S. [Univ. Wisc.-Madison; Zhou, S. [Univ. Wisc.-Madison; Place, M. [Univ. Wisc.-Madison; Zhang, Y. [Univ. Wisc.-Madison; Briska, A. [Univ. Wisc.-Madison; Goldstein, S. [Univ. Wisc.-Madison; Churas, C. [Univ. Wisc.-Madison; Runnheim, R. [Univ. Wisc.-Madison; Forrest, D. [Univ. Wisc.-Madison; Lim, A. [Univ. Wisc.-Madison; Lapidus, A. [Univ. Wisc.-Madison; Han, C. S. [Univ. Wisc.-Madison; Roberts, G. P. [Univ. Wisc.-Madison; Schwartz, D. C. [Univ. Wisc.-Madison

2005-09-01

Rhodospirillum rubrum is a phototrophic purple nonsulfur bacterium known for its unique and well-studied nitrogen fixation and carbon monoxide oxidation systems and as a source of hydrogen and biodegradable plastic production. To better understand this organism and to facilitate assembly of its sequence, three whole-genome restriction endonuclease maps (XbaI, NheI, and HindIII) of R. rubrum strain ATCC 11170 were created by optical mapping. Optical mapping is a system for creating whole-genome ordered restriction endonuclease maps from randomly sheared genomic DNA molecules extracted from cells. During the sequence finishing process, all three optical maps confirmed a putative error in sequence assembly, while the HindIII map acted as a scaffold for high-resolution alignment with sequence contigs spanning the whole genome. In addition to highlighting optical mapping's role in the assembly and confirmation of genome sequence, this work underscores the unique niche in resolution occupied by the optical mapping system. With a resolution ranging from 6.5 kb (previously published) to 45 kb (reported here), optical mapping advances a "molecular cytogenetics" approach to solving problems in genomic analysis.

Development of AMS high resolution injector system

International Nuclear Information System (INIS)

Bao Yiwen; Guan Xialing; Hu Yueming

2008-01-01

The Beijing HI-13 tandem accelerator AMS high resolution injector system was developed. The high resolution energy achromatic system consists of an electrostatic analyzer and a magnetic analyzer, which mass resolution can reach 600 and transmission is better than 80%. (authors)

Resolution enhancement of low quality videos using a high-resolution frame

NARCIS (Netherlands)

Pham, T.Q.; Van Vliet, L.J.; Schutte, K.

2006-01-01

This paper proposes an example-based Super-Resolution (SR) algorithm of compressed videos in the Discrete Cosine Transform (DCT) domain. Input to the system is a Low-Resolution (LR) compressed video together with a High-Resolution (HR) still image of similar content. Using a training set of

Highly informative multiclass profiling of lipids by ultra-high performance liquid chromatography - Low resolution (quadrupole) mass spectrometry by using electrospray ionization and atmospheric pressure chemical ionization interfaces.

Science.gov (United States)

Beccaria, Marco; Inferrera, Veronica; Rigano, Francesca; Gorynski, Krzysztof; Purcaro, Giorgia; Pawliszyn, Janusz; Dugo, Paola; Mondello, Luigi

2017-08-04

A simple, fast, and versatile method, using an ultra-high performance liquid chromatography system coupled with a low resolution (single quadrupole) mass spectrometer was optimized to perform multiclass lipid profiling of human plasma. Particular attention was made to develop a method suitable for both electrospray ionization and atmospheric pressure chemical ionization interfaces (sequentially in positive- and negative-ion mode), without any modification of the chromatographic conditions (mobile phase, flow-rate, gradient, etc.). Emphasis was given to the extrapolation of the structural information based on the fragmentation pattern obtained using atmospheric pressure chemical ionization interface, under each different ionization condition, highlighting the complementary information obtained using the electrospray ionization interface, of support for related molecule ions identification. Furthermore, mass spectra of phosphatidylserine and phosphatidylinositol obtained using the atmospheric pressure chemical ionization interface are reported and discussed for the first time. Copyright © 2017 Elsevier B.V. All rights reserved.

High resolution, high speed ultrahigh vacuum microscopy

International Nuclear Information System (INIS)

Poppa, Helmut

2004-01-01

The history and future of transmission electron microscopy (TEM) is discussed as it refers to the eventual development of instruments and techniques applicable to the real time in situ investigation of surface processes with high resolution. To reach this objective, it was necessary to transform conventional high resolution instruments so that an ultrahigh vacuum (UHV) environment at the sample site was created, that access to the sample by various in situ sample modification procedures was provided, and that in situ sample exchanges with other integrated surface analytical systems became possible. Furthermore, high resolution image acquisition systems had to be developed to take advantage of the high speed imaging capabilities of projection imaging microscopes. These changes to conventional electron microscopy and its uses were slowly realized in a few international laboratories over a period of almost 40 years by a relatively small number of researchers crucially interested in advancing the state of the art of electron microscopy and its applications to diverse areas of interest; often concentrating on the nucleation, growth, and properties of thin films on well defined material surfaces. A part of this review is dedicated to the recognition of the major contributions to surface and thin film science by these pioneers. Finally, some of the important current developments in aberration corrected electron optics and eventual adaptations to in situ UHV microscopy are discussed. As a result of all the path breaking developments that have led to today's highly sophisticated UHV-TEM systems, integrated fundamental studies are now possible that combine many traditional surface science approaches. Combined investigations to date have involved in situ and ex situ surface microscopies such as scanning tunneling microscopy/atomic force microscopy, scanning Auger microscopy, and photoemission electron microscopy, and area-integrating techniques such as x-ray photoelectron

Application of spatially resolved high resolution crystal spectrometry to inertial confinement fusion plasmas.

Science.gov (United States)

Hill, K W; Bitter, M; Delgado-Aparacio, L; Pablant, N A; Beiersdorfer, P; Schneider, M; Widmann, K; Sanchez del Rio, M; Zhang, L

2012-10-01

High resolution (λ∕Δλ ∼ 10 000) 1D imaging x-ray spectroscopy using a spherically bent crystal and a 2D hybrid pixel array detector is used world wide for Doppler measurements of ion-temperature and plasma flow-velocity profiles in magnetic confinement fusion plasmas. Meter sized plasmas are diagnosed with cm spatial resolution and 10 ms time resolution. This concept can also be used as a diagnostic of small sources, such as inertial confinement fusion plasmas and targets on x-ray light source beam lines, with spatial resolution of micrometers, as demonstrated by laboratory experiments using a 250-μm (55)Fe source, and by ray-tracing calculations. Throughput calculations agree with measurements, and predict detector counts in the range 10(-8)-10(-6) times source x-rays, depending on crystal reflectivity and spectrometer geometry. Results of the lab demonstrations, application of the technique to the National Ignition Facility (NIF), and predictions of performance on NIF will be presented.

Using high resolution tritium profiles to quantify the effects of melt on two Spitsbergen ice cores

NARCIS (Netherlands)

van der Wel, L.G.; Streurman, H.J.; Isaksson, E.; Helsen, M.M.; van de Wal, R.S.W.; Martma, T.; Pohjola, V.A.; Moore, J.C.; Meijer, H.A.J.

2011-01-01

Ice cores from small ice caps provide valuable climatic information, additional to that of Greenland and Antarctica. However, their integrity is usually compromised by summer meltwater percolation. To determine to what extent this can affect such ice cores, we performed high-resolution tritium

Using high-resolution tritium profiles to quantify the effects of melt on two Spitsbergen ice cores

NARCIS (Netherlands)

Wel, L.G. van der; Streurman, H.J.; Isaksson, E.; Helsen, M.M.; Wal, R.S.W. van de; Martma, T.; Pohjola, V.A.; Moore, J.C.; Meijer, H.A.J.

2011-01-01

Ice cores from small ice caps provide valuable climatic information, additional to that of Greenland and Antarctica. However, their integrity is usually compromised by summer meltwater percolation. To determine to what extent this can affect such ice cores, we performed high-resolution tritium

Measuring centimeter-resolution air temperature profiles above land and water using fiber-optic Distributed Temperature Sensing

Science.gov (United States)

Sigmund, Armin; Pfister, Lena; Olesch, Johannes; Thomas, Christoph K.

2016-04-01

The precise determination of near-surface air temperature profiles is of special importance for the characterization of airflows (e.g. cold air) and the quantification of sensible heat fluxes according to the flux-gradient similarity approach. In contrast to conventional multi-sensor techniques, measuring temperature profiles using fiber-optic Distributed Temperature Sensing (DTS) provides thousands of measurements referenced to a single calibration standard at much reduced costs. The aim of this work was to enhance the vertical resolution of Raman scatter DTS measurements up to the centimeter-scale using a novel approach for atmospheric applications: the optical fiber was helically coiled around a meshed fabric. In addition to testing the new fiber geometry, we quantified the measurement uncertainty and demonstrated the benefits of the enhanced-resolution profiles. The fiber-optic cable was coiled around a hollow column consisting of white reinforcing fabric supported by plexiglass rings every meter. Data from two columns of this type were collected for 47 days to measure air temperature vertically over 3.0 and 5.1 m over a gently inclined meadow and over and in a small lake, respectively. Both profiles had a vertical resolution of 1 cm in the lower section near the surface and 5 cm in the upper section with an along-fiber instrument-specific averaging of 1.0 m and a temporal resolution of 30 s. Measurement uncertainties, especially from conduction between reinforcing fabric and fiber-optic cable, were estimated by modeling the fiber temperature via a detailed energy balance approach. Air temperature, wind velocity and radiation components were needed as input data and measured separately. The temperature profiles revealed valuable details, especially in the lowest 1 m above surface. This was best demonstrated for nighttime observations when artefacts due to solar heating did not occur. For example, the dynamics of a cold air layer was detected in a clear night

D1A, a high resolution neutron powder diffractometer with a bank of mylar collimators

International Nuclear Information System (INIS)

Hewat, A.W.; Bailey, I.

1976-01-01

This paper describes a first attempt at following the design criteria set out earlier for a high resolution conventional powder diffractometer. An existing machine, D1A, has been modified using a bank of ten high pressure 3 He counters and almost perfect 10minutes of arc mylar foil collimators. The system is more successful than earlier multicollimator arrangements because each of the collimator/counters is virtually identical; this permits automatic addition of the intensities so that a single high resolution profile, up to X40 times as intense as on the original diffractometer, is obtained just as easily as on a single counter machine. A comparison is made with the other powder diffractometers, D1B and D2 at the ILL. (Auth.)

High-resolution WRF-LES simulations for real episodes: A case study for prealpine terrain

Science.gov (United States)

Hald, Cornelius; Mauder, Matthias; Laux, Patrick; Kunstmann, Harald

2017-04-01

While in most large or regional scale weather and climate models turbulence is parametrized, LES (Large Eddy Simulation) allows for the explicit modeling of turbulent structures in the atmosphere. With the exponential growth in available computing power the technique has become more and more applicable, yet it has mostly been used to model idealized scenarios. It is investigated how well WRF-LES can represent small scale weather patterns. The results are evaluated against different hydrometeorological measurements. We use WRF-LES to model the diurnal cycle for a 48 hour episode in summer over moderately complex terrain in southern Germany. The model setup uses a high resolution digital elevation model, land use and vegetation map. The atmospheric boundary conditions are set by reanalysis data. Schemes for radiation and microphysics and a land-surface model are employed. The biggest challenge in modeling arises from the high horizontal resolution of dx = 30m, since the subgrid-scale model then requires a vertical resolution dz ≈ 10m for optimal results. We observe model instabilities and present solutions like smoothing of the surface input data, careful positioning of the model domain and shortening of the model time step down to a twentieth of a second. Model results are compared to an array of various instruments including eddy covariance stations, LIDAR, RASS, SODAR, weather stations and unmanned aerial vehicles. All instruments are part of the TERENO pre-Alpine area and were employed in the orchestrated measurement campaign ScaleX in July 2015. Examination of the results show reasonable agreement between model and measurements in temperature- and moisture profiles. Modeled wind profiles are highly dependent on the vertical resolution and are in accordance with measurements only at higher wind speeds. A direct comparison of turbulence is made difficult by the purely statistical character of turbulent motions in the model.

Combined interpretation of SkyTEM and high-resolution seismic data

DEFF Research Database (Denmark)

Høyer, Anne-Sophie; Lykke-Andersen, Holger; Jørgensen, Flemming Voldum

2011-01-01

made based on AEM (SkyTEM) and high-resolution seismic data from an area covering 10 km2 in the western part of Denmark. As support for the interpretations, an exploration well was drilled to provide lithological and logging information in the form of resistivity and vertical seismic profiling. Based...... on the resistivity log, synthetic SkyTEM responses were calculated with a varying number of gate-times in order to illustrate the effect of the noise-level. At the exploration well geophysical data were compared to the lithological log; in general there is good agreement. The same tendency was recognised when Sky...

A high resolution solar atlas for fluorescence calculations

Science.gov (United States)

Hearn, M. F.; Ohlmacher, J. T.; Schleicher, D. G.

1983-01-01

The characteristics required of a solar atlas to be used for studying the fluorescence process in comets are examined. Several sources of low resolution data were combined to provide an absolutely calibrated spectrum from 2250 A to 7000A. Three different sources of high resolution data were also used to cover this same spectral range. The low resolution data were then used to put each high resolution spectrum on an absolute scale. The three high resolution spectra were then combined in their overlap regions to produce a single, absolutely calibrated high resolution spectrum over the entire spectral range.

High resolution γ-ray spectroscopy: The first 85 years

International Nuclear Information System (INIS)

Deslattes, R.D.

2000-01-01

This opening review attempts to follow the main trends in crystal diffraction spectrometry of nuclear γ rays from its 1914 beginning in Rutherford's laboratory to the ultra-high resolution instrumentation realized in the current generation of spectrometers at the Institute Laue Langeven (ILL). The authors perspective is that of an instrumentalist hoping to convey a sense of intellectual debt to a number of predecessors, each of whom realized a certain elegance in making the tools that have enabled much good science, including that to which the remainder of this workshop is dedicated. This overview follows some of the main ideas along a trajectory toward higher resolution at higher energies, thereby enabling not only the disentangling of dense spectra, but also allowing detailed study of aspects of spectral profiles sensitive to excited state lifetimes and interatomic potentials. The parallel evolution toward increasing efficiency while preserving needed resolution is also an interesting story of artful compromise that should not be neglected. Finally, it is the robustness of the measurement chain connecting γ-ray wavelengths with optical wave-lengths associated with the Rydberg constant that only recently has allowed γ-ray data to contribute to determine of particle masses and fundamental constants, as will be described in more detail in other papers from this workshop

A high-resolution map of the three-dimensional chromatin interactome in human cells.

Science.gov (United States)

Jin, Fulai; Li, Yan; Dixon, Jesse R; Selvaraj, Siddarth; Ye, Zhen; Lee, Ah Young; Yen, Chia-An; Schmitt, Anthony D; Espinoza, Celso A; Ren, Bing

2013-11-14

A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-α signalling in these cells. Unexpectedly, we found that TNF-α-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.

A high-resolution full-field range imaging system

Science.gov (United States)

Carnegie, D. A.; Cree, M. J.; Dorrington, A. A.

2005-08-01

There exist a number of applications where the range to all objects in a field of view needs to be obtained. Specific examples include obstacle avoidance for autonomous mobile robots, process automation in assembly factories, surface profiling for shape analysis, and surveying. Ranging systems can be typically characterized as being either laser scanning systems where a laser point is sequentially scanned over a scene or a full-field acquisition where the range to every point in the image is simultaneously obtained. The former offers advantages in terms of range resolution, while the latter tend to be faster and involve no moving parts. We present a system for determining the range to any object within a camera's field of view, at the speed of a full-field system and the range resolution of some point laser scans. Initial results obtained have a centimeter range resolution for a 10 second acquisition time. Modifications to the existing system are discussed that should provide faster results with submillimeter resolution.

Genomic and Metabolomic Profile Associated to Clustering of Cardio-Metabolic Risk Factors.

Science.gov (United States)

Marrachelli, Vannina G; Rentero, Pilar; Mansego, María L; Morales, Jose Manuel; Galan, Inma; Pardo-Tendero, Mercedes; Martinez, Fernando; Martin-Escudero, Juan Carlos; Briongos, Laisa; Chaves, Felipe Javier; Redon, Josep; Monleon, Daniel

2016-01-01

To identify metabolomic and genomic markers associated with the presence of clustering of cardiometabolic risk factors (CMRFs) from a general population. One thousand five hundred and two subjects, Caucasian, > 18 years, representative of the general population, were included. Blood pressure measurement, anthropometric parameters and metabolic markers were measured. Subjects were grouped according the number of CMRFs (Group 1: profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age 54±19, 50.6% men) with high genotyping call rate were analysed. A differential metabolomic profile, which included products from mitochondrial metabolism, extra mitochondrial metabolism, branched amino acids and fatty acid signals were observed among the three groups. The comparison of metabolomic patterns between subjects of Groups 1 to 3 for each of the genotypes associated to those subjects with three or more CMRFs revealed two SNPs, the rs174577_AA of FADS2 gene and the rs3803_TT of GATA2 transcription factor gene, with minimal or no statistically significant differences. Subjects with and without three or more CMRFs who shared the same genotype and metabolomic profile differed in the pattern of CMRFS cluster. Subjects of Group 3 and the AA genotype of the rs174577 had a lower prevalence of hypertension compared to the CC and CT genotype. In contrast, subjects of Group 3 and the TT genotype of the rs3803 polymorphism had a lower prevalence of T2DM, although they were predominantly males and had higher values of plasma creatinine. The results of the present study add information to the metabolomics profile and to the potential impact of genetic factors on the variants of clustering of cardiometabolic risk factors.

Genome-wide mapping of Painting of fourth on Drosophila melanogaster salivary gland polytene chromosomes.

Science.gov (United States)

Johansson, Anna-Mia; Larsson, Jan

2014-12-01

The protein Painting of fourth (POF) in Drosophila melanogaster specifically targets and stimulates expression output from the heterochromatic 4th chromosome, thereby representing an autosome specific protein [1,2]. Despite the high specificity for chromosome 4 genes, POF is occasionally observed binding to the cytological region 2L:31 in males and females [3] and two loci on the X-chromosome, PoX1 and PoX2 only in females [4]. Here we provide a detailed description of the experimental design and analysis of the tiling array data presented by Lundberg and colleagues in G3: Genes, Genomes, Genetics 2013 [4], where the female specific POF binding to PoX1 and PoX2 loci on the X chromosome was reported. We show the genome-wide high resolution binding profile of the POF protein where these different POF binding sites are detected. The complete data set is available at http://www.ncbi.nlm.nih.gov/geo/ (accession: GSE45402).

A High-Resolution LC-MS-Based Secondary Metabolite Fingerprint Database of Marine Bacteria

KAUST Repository

Lu, Liang

2014-10-09

© 2014 Macmillan Publishers Limited. All rights reserved. Marine bacteria are the most widely distributed organisms in the ocean environment and produce a wide variety of secondary metabolites. However, traditional screening for bioactive natural compounds is greatly hindered by the lack of a systematic way of cataloguing the chemical profiles of bacterial strains found in nature. Here we present a chemical fingerprint database of marine bacteria based on their secondary metabolite profiles, acquired by high-resolution LC-MS. Till now, 1,430 bacterial strains spanning 168 known species collected from different marine environments were cultured and profiled. Using this database, we demonstrated that secondary metabolite profile similarity is approximately, but not always, correlated with taxonomical similarity. We also validated the ability of this database to find species-specific metabolites, as well as to discover known bioactive compounds from previously unknown sources. An online interface to this database, as well as the accompanying software, is provided freely for the community to use.

A High-Resolution LC-MS-Based Secondary Metabolite Fingerprint Database of Marine Bacteria

KAUST Repository

Lu, Liang; Wang, Jijie; Xu, Ying; Wang, Kailing; Hu, Yingwei; Tian, Renmao; Yang, Bo; Lai, Qiliang; Li, Yongxin; Zhang, Weipeng; Shao, Zongze; Lam, Henry; Qian, Pei-Yuan

2014-01-01

© 2014 Macmillan Publishers Limited. All rights reserved. Marine bacteria are the most widely distributed organisms in the ocean environment and produce a wide variety of secondary metabolites. However, traditional screening for bioactive natural compounds is greatly hindered by the lack of a systematic way of cataloguing the chemical profiles of bacterial strains found in nature. Here we present a chemical fingerprint database of marine bacteria based on their secondary metabolite profiles, acquired by high-resolution LC-MS. Till now, 1,430 bacterial strains spanning 168 known species collected from different marine environments were cultured and profiled. Using this database, we demonstrated that secondary metabolite profile similarity is approximately, but not always, correlated with taxonomical similarity. We also validated the ability of this database to find species-specific metabolites, as well as to discover known bioactive compounds from previously unknown sources. An online interface to this database, as well as the accompanying software, is provided freely for the community to use.

High-resolution SPECT for small-animal imaging

International Nuclear Information System (INIS)

Qi Yujin

2006-01-01

This article presents a brief overview of the development of high-resolution SPECT for small-animal imaging. A pinhole collimator has been used for high-resolution animal SPECT to provide better spatial resolution and detection efficiency in comparison with a parallel-hole collimator. The theory of imaging characteristics of the pinhole collimator is presented and the designs of the pinhole aperture are discussed. The detector technologies used for the development of small-animal SPECT and the recent advances are presented. The evolving trend of small-animal SPECT is toward a multi-pinhole and a multi-detector system to obtain a high resolution and also a high detection efficiency. (authors)

Fungal Genomics Program

Energy Technology Data Exchange (ETDEWEB)

Grigoriev, Igor

2012-03-12

The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

Spatial and temporal beam profile monitor with nanosecond resolution for CERN's Linac4 and Superconducting Proton Linac

CERN Document Server

Hori, M

2008-01-01

The Linac4, now being developed at CERN, will provide 160-MeV H- beams of high intensity . Before this beam can be injected into the CERN Proton Synchrotron Booster or future Superconducting Proton Linac for further acceleration, some sequences of 500-ps-long micro-bunches must be removed from it, using a beam chopper. These bunches, if left in the beam, would fall outside the longitudinal acceptance of the accelerators and make them radioactive. We developed a monitor to measure the time structure and spatial profile of this chopped beam, with respective resolutions and . Its large active area and dynamic range also allows investigations of beam halos. The ion beam first struck a carbon foil, and secondary electrons emerging from the foil were accelerated by a series of parallel grid electrodes. These electrons struck a phosphor screen, and the resulting image of the scintillation light was guided to a thermoelectrically cooled, charge-coupled device camera. The time resolution was attained by applying high-...

Editor's Highlight: High-Throughput Functional Genomics Identifies Modulators of TCE Metabolite Genotoxicity and Candidate Susceptibility Genes.

Science.gov (United States)

De La Rosa, Vanessa Y; Asfaha, Jonathan; Fasullo, Michael; Loguinov, Alex; Li, Peng; Moore, Lee E; Rothman, Nathaniel; Nakamura, Jun; Swenberg, James A; Scelo, Ghislaine; Zhang, Luoping; Smith, Martyn T; Vulpe, Chris D

2017-11-01

Trichloroethylene (TCE), an industrial chemical and environmental contaminant, is a human carcinogen. Reactive metabolites are implicated in renal carcinogenesis associated with TCE exposure, yet the toxicity mechanisms of these metabolites and their contribution to cancer and other adverse effects remain unclear. We employed an integrated functional genomics approach that combined functional profiling studies in yeast and avian DT40 cell models to provide new insights into the specific mechanisms contributing to toxicity associated with TCE metabolites. Genome-wide profiling studies in yeast identified the error-prone translesion synthesis (TLS) pathway as an import mechanism in response to TCE metabolites. The role of TLS DNA repair was further confirmed by functional profiling in DT40 avian cell lines, but also revealed that TLS and homologous recombination DNA repair likely play competing roles in cellular susceptibility to TCE metabolites in higher eukaryotes. These DNA repair pathways are highly conserved between yeast, DT40, and humans. We propose that in humans, mutagenic TLS is favored over homologous recombination repair in response to TCE metabolites. The results of these studies contribute to the body of evidence supporting a mutagenic mode of action for TCE-induced renal carcinogenesis mediated by reactive metabolites in humans. Our approach illustrates the potential for high-throughput in vitro functional profiling in yeast to elucidate toxicity pathways (molecular initiating events, key events) and candidate susceptibility genes for focused study. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Design, Construction, and Initial Test of High Spatial Resolution Thermometry Arrays for Detection of Surface Temperature Profiles on SRF Cavities in Super Fluid Helium

Energy Technology Data Exchange (ETDEWEB)

Ari Palczewski, Rongli Geng, Grigory Eremeev

2011-07-01

We designed and built two high resolution (0.6-0.55mm special resolution [1.1-1.2mm separation]) thermometry arrays prototypes out of the Allen Bradley 90-120 ohm 1/8 watt resistor to measure surface temperature profiles on SRF cavities. One array was designed to be physically flexible and conform to any location on a SRF cavity; the other was modeled after the common G-10/stycast 2850 thermometer and designed to fit on the equator of an ILC (Tesla 1.3GHz) SRF cavity. We will discuss the advantages and disadvantages of each array and their construction. In addition we will present a case study of the arrays performance on a real SRF cavity TB9NR001. TB9NR001 presented a unique opportunity to test the performance of each array as it contained a dual (4mm separation) cat eye defect which conventional methods such as OST (Oscillating Superleak second-sound Transducers) and full coverage thermometry mapping were unable to distinguish between. We will discuss the new arrays ability to distinguish between the two defects and their preheating performance.

Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology

DEFF Research Database (Denmark)

Cao, Hongzhi; Hastie, Alex R.; Cao, Dandan

2014-01-01

mutations; however, none of the current detection methods are comprehensive, and currently available methodologies are incapable of providing sufficient resolution and unambiguous information across complex regions in the human genome. To address these challenges, we applied a high-throughput, cost......-effective genome mapping technology to comprehensively discover genome-wide SVs and characterize complex regions of the YH genome using long single molecules (>150 kb) in a global fashion. RESULTS: Utilizing nanochannel-based genome mapping technology, we obtained 708 insertions/deletions and 17 inversions larger...... fosmid data. Of the remaining 270 SVs, 260 are insertions and 213 overlap known SVs in the Database of Genomic Variants. Overall, 609 out of 666 (90%) variants were supported by experimental orthogonal methods or historical evidence in public databases. At the same time, genome mapping also provides...

Epigenomics of Total Acute Sleep Deprivation in Relation to Genome-Wide DNA Methylation Profiles and RNA Expression

OpenAIRE

Nilsson, Emil K.; Bostr?m, Adrian E.; Mwinyi, Jessica; Schi?th, Helgi B.

2016-01-01

Abstract Despite an established link between sleep deprivation and epigenetic processes in humans, it remains unclear to what extent sleep deprivation modulates DNA methylation. We performed a within-subject randomized blinded study with 16 healthy subjects to examine the effect of one night of total sleep deprivation (TSD) on the genome-wide methylation profile in blood compared with that in normal sleep. Genome-wide differences in methylation between both conditions were assessed by applyin...

Deep whole-genome sequencing of 90 Han Chinese genomes.

Science.gov (United States)

Lan, Tianming; Lin, Haoxiang; Zhu, Wenjuan; Laurent, Tellier Christian Asker Melchior; Yang, Mengcheng; Liu, Xin; Wang, Jun; Wang, Jian; Yang, Huanming; Xu, Xun; Guo, Xiaosen

2017-09-01

Next-generation sequencing provides a high-resolution insight into human genetic information. However, the focus of previous studies has primarily been on low-coverage data due to the high cost of sequencing. Although the 1000 Genomes Project and the Haplotype Reference Consortium have both provided powerful reference panels for imputation, low-frequency and novel variants remain difficult to discover and call with accuracy on the basis of low-coverage data. Deep sequencing provides an optimal solution for the problem of these low-frequency and novel variants. Although whole-exome sequencing is also a viable choice for exome regions, it cannot account for noncoding regions, sometimes resulting in the absence of important, causal variants. For Han Chinese populations, the majority of variants have been discovered based upon low-coverage data from the 1000 Genomes Project. However, high-coverage, whole-genome sequencing data are limited for any population, and a large amount of low-frequency, population-specific variants remain uncharacterized. We have performed whole-genome sequencing at a high depth (∼×80) of 90 unrelated individuals of Chinese ancestry, collected from the 1000 Genomes Project samples, including 45 Northern Han Chinese and 45 Southern Han Chinese samples. Eighty-three of these 90 have been sequenced by the 1000 Genomes Project. We have identified 12 568 804 single nucleotide polymorphisms, 2 074 210 short InDels, and 26 142 structural variations from these 90 samples. Compared to the Han Chinese data from the 1000 Genomes Project, we have found 7 000 629 novel variants with low frequency (defined as minor allele frequency genome. Compared to the 1000 Genomes Project, these Han Chinese deep sequencing data enhance the characterization of a large number of low-frequency, novel variants. This will be a valuable resource for promoting Chinese genetics research and medical development. Additionally, it will provide a valuable supplement to the 1000

High-resolution passive sampling of dissolved methane in the water column of lakes in Greenland

Science.gov (United States)

Goldman, A. E.; Cadieux, S. B.; White, J. R.; Pratt, L. M.

2013-12-01

Arctic lakes are important participants in the global carbon cycle, releasing methane in a warming climate and contributing to a positive feedback to climate change. In order to yield detailed methane budgets and understand the implications of warming on methane dynamics, high-resolution profiles revealing methane behavior within the water column need to be obtained. Single day sampling using disruptive techniques has the potential to result in biases. In order to obtain high-resolution, undisturbed profiles of methane concentration and isotopic composition, this study evaluates a passive sampling method over a multi-day equilibration period. Selected for this study were two small lakes (Gatos Research Methane Carbon Isotope Analyzer. PDB sampling and pump sampling resulted in statistically similar concentrations (R2=0.89), ranging from 0.85 to 135 uM from PDB and 0.74 to 143 uM from pump sampling. In anoxic waters of the lake, where concentrations were high enough to yield robust isotopic results on the LGR MCIA, δ13C were also similar between the two methods, yielding -73‰ from PDB and -74‰ from pump sampling. Further investigation will produce results for a second lake and methane carbon and hydrogen isotopic composition for both lakes. Preliminary results for this passive sampling method are promising. We envision the use of this technique in future studies of dissolved methane and expect that it will provide a more finely resolved vertical profile, allowing for a more complete understanding of lacustrine methane dynamics.

Finished Genome Sequence of Collimonas arenae Cal35

NARCIS (Netherlands)

Wu, Je-Jia; de Jager, Victor; Deng, Wen-ling; Leveau, Johan

2015-01-01

We announce the finished genome sequence of soil forest isolate Collimonas arenae Cal35, which comprises a 5.6-Mbp chromosome and 41-kb plasmid. The Cal35 genome is the second one published for the bacterial genus Collimonas and represents the first opportunity for high-resolution comparison of

GI-POP: a combinational annotation and genomic island prediction pipeline for ongoing microbial genome projects.

Science.gov (United States)

Lee, Chi-Ching; Chen, Yi-Ping Phoebe; Yao, Tzu-Jung; Ma, Cheng-Yu; Lo, Wei-Cheng; Lyu, Ping-Chiang; Tang, Chuan Yi

2013-04-10

Sequencing of microbial genomes is important because of microbial-carrying antibiotic and pathogenetic activities. However, even with the help of new assembling software, finishing a whole genome is a time-consuming task. In most bacteria, pathogenetic or antibiotic genes are carried in genomic islands. Therefore, a quick genomic island (GI) prediction method is useful for ongoing sequencing genomes. In this work, we built a Web server called GI-POP (http://gipop.life.nthu.edu.tw) which integrates a sequence assembling tool, a functional annotation pipeline, and a high-performance GI predicting module, in a support vector machine (SVM)-based method called genomic island genomic profile scanning (GI-GPS). The draft genomes of the ongoing genome projects in contigs or scaffolds can be submitted to our Web server, and it provides the functional annotation and highly probable GI-predicting results. GI-POP is a comprehensive annotation Web server designed for ongoing genome project analysis. Researchers can perform annotation and obtain pre-analytic information include possible GIs, coding/non-coding sequences and functional analysis from their draft genomes. This pre-analytic system can provide useful information for finishing a genome sequencing project. Copyright © 2012 Elsevier B.V. All rights reserved.

The PiGeOn project: protocol for a longitudinal study examining psychosocial, behavioural and ethical issues and outcomes in cancer tumour genomic profiling.

Science.gov (United States)

Best, Megan; Newson, Ainsley J; Meiser, Bettina; Juraskova, Ilona; Goldstein, David; Tucker, Kathy; Ballinger, Mandy L; Hess, Dominique; Schlub, Timothy E; Biesecker, Barbara; Vines, Richard; Vines, Kate; Thomas, David; Young, Mary-Anne; Savard, Jacqueline; Jacobs, Chris; Butow, Phyllis

2018-04-05

Genomic sequencing in cancer (both tumour and germline), and development of therapies targeted to tumour genetic status, hold great promise for improvement of patient outcomes. However, the imminent introduction of genomics into clinical practice calls for better understanding of how patients value, experience, and cope with this novel technology and its often complex results. Here we describe a protocol for a novel mixed-methods, prospective study (PiGeOn) that aims to examine patients' psychosocial, cognitive, affective and behavioural responses to tumour genomic profiling and to integrate a parallel critical ethical analysis of returning results. This is a cohort sub-study of a parent tumour genomic profiling programme enrolling patients with advanced cancer. One thousand patients will be recruited for the parent study in Sydney, Australia from 2016 to 2019. They will be asked to complete surveys at baseline, three, and five months. Primary outcomes are: knowledge, preferences, attitudes and values. A purposively sampled subset of patients will be asked to participate in three semi-structured interviews (at each time point) to provide deeper data interpretation. Relevant ethical themes will be critically analysed to iteratively develop or refine normative ethical concepts or frameworks currently used in the return of genetic information. This will be the first Australian study to collect longitudinal data on cancer patients' experience of tumour genomic profiling. Findings will be used to inform ongoing ethical debates on issues such as how to effectively obtain informed consent for genomic profiling return results, distinguish between research and clinical practice and manage patient expectations. The combination of quantitative and qualitative methods will provide comprehensive and critical data on how patients cope with 'actionable' and 'non-actionable' results. This information is needed to ensure that when tumour genomic profiling becomes part of routine

High resolution time integration for SN radiation transport

International Nuclear Information System (INIS)

Thoreson, Greg; McClarren, Ryan G.; Chang, Jae H.

2009-01-01

First-order, second-order, and high resolution time discretization schemes are implemented and studied for the discrete ordinates (S N ) equations. The high resolution method employs a rate of convergence better than first-order, but also suppresses artificial oscillations introduced by second-order schemes in hyperbolic partial differential equations. The high resolution method achieves these properties by nonlinearly adapting the time stencil to use a first-order method in regions where oscillations could be created. We employ a quasi-linear solution scheme to solve the nonlinear equations that arise from the high resolution method. All three methods were compared for accuracy and convergence rates. For non-absorbing problems, both second-order and high resolution converged to the same solution as the first-order with better convergence rates. High resolution is more accurate than first-order and matches or exceeds the second-order method

High resolution polarimeter-interferometer system for fast equilibrium dynamics and MHD instability studies on Joint-TEXT tokamak (invited)

Energy Technology Data Exchange (ETDEWEB)

Chen, J.; Zhuang, G., E-mail: ge-zhuang@hust.edu.cn; Li, Q.; Liu, Y.; Gao, L.; Zhou, Y. N.; Jian, X.; Xiong, C. Y.; Wang, Z. J. [State Key Laboratory of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China); Brower, D. L.; Ding, W. X. [Department of Physics and Astronomy, University of California Los Angeles, Los Angeles, California 90095 (United States)

2014-11-15

A high-performance Faraday-effect polarimeter-interferometer system has been developed for the J-TEXT tokamak. This system has time response up to 1 μs, phase resolution < 0.1° and minimum spatial resolution ∼15 mm. High resolution permits investigation of fast equilibrium dynamics as well as magnetic and density perturbations associated with intrinsic Magneto-Hydro-Dynamic (MHD) instabilities and external coil-induced Resonant Magnetic Perturbations (RMP). The 3-wave technique, in which the line-integrated Faraday angle and electron density are measured simultaneously by three laser beams with specific polarizations and frequency offsets, is used. In order to achieve optimum resolution, three frequency-stabilized HCOOH lasers (694 GHz, >35 mW per cavity) and sensitive Planar Schottky Diode mixers are used, providing stable intermediate-frequency signals (0.5–3 MHz) with S/N > 50. The collinear R- and L-wave probe beams, which propagate through the plasma poloidal cross section (a = 0.25–0.27 m) vertically, are expanded using parabolic mirrors to cover the entire plasma column. Sources of systematic errors, e.g., stemming from mechanical vibration, beam non-collinearity, and beam polarization distortion are individually examined and minimized to ensure measurement accuracy. Simultaneous density and Faraday measurements have been successfully achieved for 14 chords. Based on measurements, temporal evolution of safety factor profile, current density profile, and electron density profile are resolved. Core magnetic and density perturbations associated with MHD tearing instabilities are clearly detected. Effects of non-axisymmetric 3D RMP in ohmically heated plasmas are directly observed by polarimetry for the first time.

High tracking resolution detectors. Final Technical Report

International Nuclear Information System (INIS)

Vasile, Stefan; Li, Zheng

2010-01-01

High-resolution tracking detectors based on Active Pixel Sensor (APS) have been valuable tools in Nuclear Physics and High-Energy Physics research, and have contributed to major discoveries. Their integration time, radiation length and readout rate is a limiting factor for the planed luminosity upgrades in nuclear and high-energy physics collider-based experiments. The goal of this program was to demonstrate and develop high-gain, high-resolution tracking detector arrays with faster readout, and shorter radiation length than APS arrays. These arrays may operate as direct charged particle detectors or as readouts of high resolution scintillating fiber arrays. During this program, we developed in CMOS large, high-resolution pixel sensor arrays with integrated readout, and reset at pixel level. Their intrinsic gain, high immunity to surface and moisture damage, will allow operating these detectors with minimal packaging/passivation requirements and will result in radiation length superior to APS. In Phase I, we designed and fabricated arrays with calorimetric output capable of sub-pixel resolution and sub-microsecond readout rate. The technical effort was dedicated to detector and readout structure development, performance verification, as well as to radiation damage and damage annealing.

High resolution 3D imaging of synchrotron generated microbeams

Energy Technology Data Exchange (ETDEWEB)

Gagliardi, Frank M., E-mail: frank.gagliardi@wbrc.org.au [Alfred Health Radiation Oncology, The Alfred, Melbourne, Victoria 3004, Australia and School of Medical Sciences, RMIT University, Bundoora, Victoria 3083 (Australia); Cornelius, Iwan [Imaging and Medical Beamline, Australian Synchrotron, Clayton, Victoria 3168, Australia and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, New South Wales 2500 (Australia); Blencowe, Anton [Division of Health Sciences, School of Pharmacy and Medical Sciences, The University of South Australia, Adelaide, South Australia 5000, Australia and Division of Information Technology, Engineering and the Environment, Mawson Institute, University of South Australia, Mawson Lakes, South Australia 5095 (Australia); Franich, Rick D. [School of Applied Sciences and Health Innovations Research Institute, RMIT University, Melbourne, Victoria 3000 (Australia); Geso, Moshi [School of Medical Sciences, RMIT University, Bundoora, Victoria 3083 (Australia)

2015-12-15

Purpose: Microbeam radiation therapy (MRT) techniques are under investigation at synchrotrons worldwide. Favourable outcomes from animal and cell culture studies have proven the efficacy of MRT. The aim of MRT researchers currently is to progress to human clinical trials in the near future. The purpose of this study was to demonstrate the high resolution and 3D imaging of synchrotron generated microbeams in PRESAGE® dosimeters using laser fluorescence confocal microscopy. Methods: Water equivalent PRESAGE® dosimeters were fabricated and irradiated with microbeams on the Imaging and Medical Beamline at the Australian Synchrotron. Microbeam arrays comprised of microbeams 25–50 μm wide with 200 or 400 μm peak-to-peak spacing were delivered as single, cross-fire, multidirectional, and interspersed arrays. Imaging of the dosimeters was performed using a NIKON A1 laser fluorescence confocal microscope. Results: The spatial fractionation of the MRT beams was clearly visible in 2D and up to 9 mm in depth. Individual microbeams were easily resolved with the full width at half maximum of microbeams measured on images with resolutions of as low as 0.09 μm/pixel. Profiles obtained demonstrated the change of the peak-to-valley dose ratio for interspersed MRT microbeam arrays and subtle variations in the sample positioning by the sample stage goniometer were measured. Conclusions: Laser fluorescence confocal microscopy of MRT irradiated PRESAGE® dosimeters has been validated in this study as a high resolution imaging tool for the independent spatial and geometrical verification of MRT beam delivery.

High resolution 3D imaging of synchrotron generated microbeams

International Nuclear Information System (INIS)

Gagliardi, Frank M.; Cornelius, Iwan; Blencowe, Anton; Franich, Rick D.; Geso, Moshi

2015-01-01

Purpose: Microbeam radiation therapy (MRT) techniques are under investigation at synchrotrons worldwide. Favourable outcomes from animal and cell culture studies have proven the efficacy of MRT. The aim of MRT researchers currently is to progress to human clinical trials in the near future. The purpose of this study was to demonstrate the high resolution and 3D imaging of synchrotron generated microbeams in PRESAGE® dosimeters using laser fluorescence confocal microscopy. Methods: Water equivalent PRESAGE® dosimeters were fabricated and irradiated with microbeams on the Imaging and Medical Beamline at the Australian Synchrotron. Microbeam arrays comprised of microbeams 25–50 μm wide with 200 or 400 μm peak-to-peak spacing were delivered as single, cross-fire, multidirectional, and interspersed arrays. Imaging of the dosimeters was performed using a NIKON A1 laser fluorescence confocal microscope. Results: The spatial fractionation of the MRT beams was clearly visible in 2D and up to 9 mm in depth. Individual microbeams were easily resolved with the full width at half maximum of microbeams measured on images with resolutions of as low as 0.09 μm/pixel. Profiles obtained demonstrated the change of the peak-to-valley dose ratio for interspersed MRT microbeam arrays and subtle variations in the sample positioning by the sample stage goniometer were measured. Conclusions: Laser fluorescence confocal microscopy of MRT irradiated PRESAGE® dosimeters has been validated in this study as a high resolution imaging tool for the independent spatial and geometrical verification of MRT beam delivery

Ultra high resolution tomography

Energy Technology Data Exchange (ETDEWEB)

Haddad, W.S.

1994-11-15

Recent work and results on ultra high resolution three dimensional imaging with soft x-rays will be presented. This work is aimed at determining microscopic three dimensional structure of biological and material specimens. Three dimensional reconstructed images of a microscopic test object will be presented; the reconstruction has a resolution on the order of 1000 A in all three dimensions. Preliminary work with biological samples will also be shown, and the experimental and numerical methods used will be discussed.

Competitive PCR-High Resolution Melting Analysis (C-PCR-HRMA) for large genomic rearrangements (LGRs) detection: A new approach to assess quantitative status of BRCA1 gene in a reference laboratory.

Science.gov (United States)

Minucci, Angelo; De Paolis, Elisa; Concolino, Paola; De Bonis, Maria; Rizza, Roberta; Canu, Giulia; Scaglione, Giovanni Luca; Mignone, Flavio; Scambia, Giovanni; Zuppi, Cecilia; Capoluongo, Ettore

2017-07-01

Evaluation of copy number variation (CNV) in BRCA1/2 genes, due to large genomic rearrangements (LGRs), is a mandatory analysis in hereditary breast and ovarian cancers families, if no pathogenic variants are found by sequencing. LGRs cannot be detected by conventional methods and several alternative methods have been developed. Since these approaches are expensive and time consuming, identification of alternative screening methods for LGRs detection is needed in order to reduce and optimize the diagnostic procedure. The aim of this study was to investigate a Competitive PCR-High Resolution Melting Analysis (C-PCR-HRMA) as molecular tool to detect recurrent BRCA1 LGRs. C-PCR-HRMA was performed on exons 3, 14, 18, 19, 20 and 21 of the BRCA1 gene; exons 4, 6 and 7 of the ALB gene were used as reference fragments. This study showed that it is possible to identify recurrent BRCA1 LGRs, by melting peak height ratio between target (BRCA1) and reference (ALB) fragments. Furthermore, we underline that a peculiar amplicon-melting profile is associated to a specific BRCA1 LGR. All C-PCR-HRMA results were confirmed by Multiplex ligation-dependent probe amplification. C-PCR-HRMA has proved to be an innovative, efficient and fast method for BRCA1 LGRs detection. Given the sensitivity, specificity and ease of use, c-PCR-HRMA can be considered an attractive and powerful alternative to other methods for BRCA1 CNVs screening, improving molecular strategies for BRCA testing in the context of Massive Parallel Sequencing. Copyright © 2017 Elsevier B.V. All rights reserved.

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

NARCIS (Netherlands)

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it

Genome-wide mapping of DNA strand breaks.

Directory of Open Access Journals (Sweden)

Frédéric Leduc

Full Text Available Determination of cellular DNA damage has so far been limited to global assessment of genome integrity whereas nucleotide-level mapping has been restricted to specific loci by the use of specific primers. Therefore, only limited DNA sequences can be studied and novel regions of genomic instability can hardly be discovered. Using a well-characterized yeast model, we describe a straightforward strategy to map genome-wide DNA strand breaks without compromising nucleotide-level resolution. This technique, termed "damaged DNA immunoprecipitation" (dDIP, uses immunoprecipitation and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labeling (TUNEL to capture DNA at break sites. When used in combination with microarray or next-generation sequencing technologies, dDIP will allow researchers to map genome-wide DNA strand breaks as well as other types of DNA damage and to establish a clear profiling of altered genes and/or intergenic sequences in various experimental conditions. This mapping technique could find several applications for instance in the study of aging, genotoxic drug screening, cancer, meiosis, radiation and oxidative DNA damage.

TEGS-CN: A Statistical Method for Pathway Analysis of Genome-wide Copy Number Profile.

Science.gov (United States)

Huang, Yen-Tsung; Hsu, Thomas; Christiani, David C

2014-01-01

The effects of copy number alterations make up a significant part of the tumor genome profile, but pathway analyses of these alterations are still not well established. We proposed a novel method to analyze multiple copy numbers of genes within a pathway, termed Test for the Effect of a Gene Set with Copy Number data (TEGS-CN). TEGS-CN was adapted from TEGS, a method that we previously developed for gene expression data using a variance component score test. With additional development, we extend the method to analyze DNA copy number data, accounting for different sizes and thus various numbers of copy number probes in genes. The test statistic follows a mixture of X (2) distributions that can be obtained using permutation with scaled X (2) approximation. We conducted simulation studies to evaluate the size and the power of TEGS-CN and to compare its performance with TEGS. We analyzed a genome-wide copy number data from 264 patients of non-small-cell lung cancer. With the Molecular Signatures Database (MSigDB) pathway database, the genome-wide copy number data can be classified into 1814 biological pathways or gene sets. We investigated associations of the copy number profile of the 1814 gene sets with pack-years of cigarette smoking. Our analysis revealed five pathways with significant P values after Bonferroni adjustment (number data, and causal mechanisms of the five pathways require further study.

Rapid Detection and Differentiation of Clonorchis sinensis and Opisthorchis viverrini Using Real-Time PCR and High Resolution Melting Analysis

OpenAIRE

Cai, Xian-Quan; Yu, Hai-Qiong; Li, Rong; Yue, Qiao-Yun; Liu, Guo-Hua; Bai, Jian-Shan; Deng, Yan; Qiu, De-Yi; Zhu, Xing-Quan

2014-01-01

Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA...

Estimating NOx emissions and surface concentrations at high spatial resolution using OMI

Science.gov (United States)

Goldberg, D. L.; Lamsal, L. N.; Loughner, C.; Swartz, W. H.; Saide, P. E.; Carmichael, G. R.; Henze, D. K.; Lu, Z.; Streets, D. G.

2017-12-01

In many instances, NOx emissions are not measured at the source. In these cases, remote sensing techniques are extremely useful in quantifying NOx emissions. Using an exponential modified Gaussian (EMG) fitting of oversampled Ozone Monitoring Instrument (OMI) NO2 data, we estimate NOx emissions and lifetimes in regions where these emissions are uncertain. This work also presents a new high-resolution OMI NO2 dataset derived from the NASA retrieval that can be used to estimate surface level concentrations in the eastern United States and South Korea. To better estimate vertical profile shape factors, we use high-resolution model simulations (Community Multi-scale Air Quality (CMAQ) and WRF-Chem) constrained by in situ aircraft observations to re-calculate tropospheric air mass factors and tropospheric NO2 vertical columns during summertime. The correlation between our satellite product and ground NO2 monitors in urban areas has improved dramatically: r2 = 0.60 in new product, r2 = 0.39 in operational product, signifying that this new product is a better indicator of surface concentrations than the operational product. Our work emphasizes the need to use both high-resolution and high-fidelity models in order to re-calculate vertical column data in areas with large spatial heterogeneities in NOx emissions. The methodologies developed in this work can be applied to other world regions and other satellite data sets to produce high-quality region-specific emissions estimates.

Tandem repeat regions within the Burkholderia pseudomallei genome and their application for high resolution genotyping

Directory of Open Access Journals (Sweden)

Harvey Steven P

2007-03-01

Full Text Available Abstract Background The facultative, intracellular bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease of humans and animals. We identified and categorized tandem repeat arrays and their distribution throughout the genome of B. pseudomallei strain K96243 in order to develop a genetic typing method for B. pseudomallei. We then screened 104 of the potentially polymorphic loci across a diverse panel of 31 isolates including B. pseudomallei, B. mallei and B. thailandensis in order to identify loci with varying degrees of polymorphism. A subset of these tandem repeat arrays were subsequently developed into a multiple-locus VNTR analysis to examine 66 B. pseudomallei and 21 B. mallei isolates from around the world, as well as 95 lineages from a serial transfer experiment encompassing ~18,000 generations. Results B. pseudomallei contains a preponderance of tandem repeat loci throughout its genome, many of which are duplicated elsewhere in the genome. The majority of these loci are composed of repeat motif lengths of 6 to 9 bp with 4 to 10 repeat units and are predominately located in intergenic regions of the genome. Across geographically diverse B. pseudomallei and B.mallei isolates, the 32 VNTR loci displayed between 7 and 28 alleles, with Nei's diversity values ranging from 0.47 and 0.94. Mutation rates for these loci are comparable (>10-5 per locus per generation to that of the most diverse tandemly repeated regions found in other less diverse bacteria. Conclusion The frequency, location and duplicate nature of tandemly repeated regions within the B. pseudomallei genome indicate that these tandem repeat regions may play a role in generating and maintaining adaptive genomic variation. Multiple-locus VNTR analysis revealed extensive diversity within the global isolate set containing B. pseudomallei and B. mallei, and it detected genotypic differences within clonal lineages of both species that were

A high resolution portable spectroscopy system

International Nuclear Information System (INIS)

Kulkarni, C.P.; Vaidya, P.P.; Paulson, M.; Bhatnagar, P.V.; Pande, S.S.; Padmini, S.

2003-01-01

Full text: This paper describes the system details of a High Resolution Portable Spectroscopy System (HRPSS) developed at Electronics Division, BARC. The system can be used for laboratory class, high-resolution nuclear spectroscopy applications. The HRPSS consists of a specially designed compact NIM bin, with built-in power supplies, accommodating a low power, high resolution MCA, and on-board embedded computer for spectrum building and communication. A NIM based spectroscopy amplifier and a HV module for detector bias are integrated (plug-in) in the bin. The system communicates with a host PC via a serial link. Along-with a laptop PC, and a portable HP-Ge detector, the HRPSS offers a laboratory class performance for portable applications

High resolution laser spectroscopy as a diagnostic tool in beams

International Nuclear Information System (INIS)

Bergmann, K.; Hefter, U.; Hering, P.

1977-01-01

The combination of high resolution laser spectroscopy with the technique of molecular beams allows a very detailed beam research since molecules or atoms in specific quantum states can be sampled yielding previously unavailable sources of data. In these experiments a Na/Na 2 beam emerges from a 0.2 mm nozzle and is collimated by a 2 mm wide slit 50 cm downstream. To probe the molecules a single mode Ar + -laser was used which can be tuned within the gain profile of the laser line (8 GHz) to several transitions between specific levels in the ground state and second electronically excited state of the Na 2 molecule. (Auth.)

Sub-nanometer resolution XPS depth profiling: Sensing of atoms

Energy Technology Data Exchange (ETDEWEB)

Szklarczyk, Marek, E-mail: szklarcz@chem.uw.edu.pl [Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02-093 Warsaw (Poland); Shim-Pol, ul. Lubomirskiego 5, 05-080 Izabelin (Poland); Macak, Karol; Roberts, Adam J. [Kratos Analytical Ltd, Wharfside, Trafford Wharf Road, Manchester, M17 1GP (United Kingdom); Takahashi, Kazuhiro [Kratos XPS Section, Shimadzu Corp., 380-1 Horiyamashita, Hadano, Kanagawa 259-1304 (Japan); Hutton, Simon [Kratos Analytical Ltd, Wharfside, Trafford Wharf Road, Manchester, M17 1GP (United Kingdom); Głaszczka, Rafał [Shim-Pol, ul. Lubomirskiego 5, 05-080 Izabelin (Poland); Blomfield, Christopher [Kratos Analytical Ltd, Wharfside, Trafford Wharf Road, Manchester, M17 1GP (United Kingdom)

2017-07-31

Highlights: • Angle resolved photoelectron depth profiling of nano thin films. • Sensing atomic position in SAM films. • Detection of direction position of adsorbed molecules. - Abstract: The development of a method capable of distinguishing a single atom in a single molecule is important in many fields. The results reported herein demonstrate sub-nanometer resolution for angularly resolved X-ray photoelectron spectroscopy (ARXPS). This is made possible by the incorporation of a Maximum Entropy Method (MEM) model, which utilize density corrected electronic emission factors to the X-ray photoelectron spectroscopy (XPS) experimental results. In this paper we report on the comparison between experimental ARXPS results and reconstructed for both inorganic and organic thin film samples. Unexpected deviations between experimental data and calculated points are explained by the inaccuracy of the constants and standards used for the calculation, e.g. emission factors, scattering intensity and atomic density through the studied thickness. The positions of iron, nitrogen and fluorine atoms were determined in the molecules of the studied self-assembled monolayers. It has been shown that reconstruction of real spectroscopic data with 0.2 nm resolution is possible.

Mitochondrial Genome Sequences and Structures Aid in the Resolution of Piroplasmida phylogeny

Science.gov (United States)

Marr, Henry S.; Tarigo, Jaime L.; Cohn, Leah A.; Bird, David M.; Scholl, Elizabeth H.; Levy, Michael G.; Wiegmann, Brian M.; Birkenheuer, Adam J.

2016-01-01

The taxonomy of the order Piroplasmida, which includes a number of clinically and economically relevant organisms, is a hotly debated topic amongst parasitologists. Three genera (Babesia, Theileria, and Cytauxzoon) are recognized based on parasite life cycle characteristics, but molecular phylogenetic analyses of 18S sequences have suggested the presence of five or more distinct Piroplasmida lineages. Despite these important advancements, a few studies have been unable to define the taxonomic relationships of some organisms (e.g. C. felis and T. equi) with respect to other Piroplasmida. Additional evidence from mitochondrial genome sequences and synteny should aid in the inference of Piroplasmida phylogeny and resolution of taxonomic uncertainties. In this study, we have amplified, sequenced, and annotated seven previously uncharacterized mitochondrial genomes (Babesia canis, Babesia vogeli, Babesia rossi, Babesia sp. Coco, Babesia conradae, Babesia microti-like sp., and Cytauxzoon felis) and identified additional ribosomal fragments in ten previously characterized mitochondrial genomes. Phylogenetic analysis of concatenated mitochondrial and 18S sequences as well as cox1 amino acid sequence identified five distinct Piroplasmida groups, each of which possesses a unique mitochondrial genome structure. Specifically, our results confirm the existence of four previously identified clades (B. microti group, Babesia sensu stricto, Theileria equi, and a Babesia sensu latu group that includes B. conradae) while supporting the integration of Theileria and Cytauxzoon species into a single fifth taxon. Although known biological characteristics of Piroplasmida corroborate the proposed phylogeny, more investigation into parasite life cycles is warranted to further understand the evolution of the Piroplasmida. Our results provide an evolutionary framework for comparative biology of these important animal and human pathogens and help focus renewed efforts toward understanding the

Mitochondrial Genome Sequences and Structures Aid in the Resolution of Piroplasmida phylogeny.

Directory of Open Access Journals (Sweden)

Megan E Schreeg

Full Text Available The taxonomy of the order Piroplasmida, which includes a number of clinically and economically relevant organisms, is a hotly debated topic amongst parasitologists. Three genera (Babesia, Theileria, and Cytauxzoon are recognized based on parasite life cycle characteristics, but molecular phylogenetic analyses of 18S sequences have suggested the presence of five or more distinct Piroplasmida lineages. Despite these important advancements, a few studies have been unable to define the taxonomic relationships of some organisms (e.g. C. felis and T. equi with respect to other Piroplasmida. Additional evidence from mitochondrial genome sequences and synteny should aid in the inference of Piroplasmida phylogeny and resolution of taxonomic uncertainties. In this study, we have amplified, sequenced, and annotated seven previously uncharacterized mitochondrial genomes (Babesia canis, Babesia vogeli, Babesia rossi, Babesia sp. Coco, Babesia conradae, Babesia microti-like sp., and Cytauxzoon felis and identified additional ribosomal fragments in ten previously characterized mitochondrial genomes. Phylogenetic analysis of concatenated mitochondrial and 18S sequences as well as cox1 amino acid sequence identified five distinct Piroplasmida groups, each of which possesses a unique mitochondrial genome structure. Specifically, our results confirm the existence of four previously identified clades (B. microti group, Babesia sensu stricto, Theileria equi, and a Babesia sensu latu group that includes B. conradae while supporting the integration of Theileria and Cytauxzoon species into a single fifth taxon. Although known biological characteristics of Piroplasmida corroborate the proposed phylogeny, more investigation into parasite life cycles is warranted to further understand the evolution of the Piroplasmida. Our results provide an evolutionary framework for comparative biology of these important animal and human pathogens and help focus renewed efforts toward

Streptococcus iniae SF1: complete genome sequence, proteomic profile, and immunoprotective antigens.

Directory of Open Access Journals (Sweden)

Bao-cun Zhang

Full Text Available Streptococcus iniae is a Gram-positive bacterium that is reckoned one of the most severe aquaculture pathogens. It has a broad host range among farmed marine and freshwater fish and can also cause zoonotic infection in humans. Here we report for the first time the complete genome sequence as well as the host factor-induced proteomic profile of a pathogenic S. iniae strain, SF1, a serotype I isolate from diseased fish. SF1 possesses a single chromosome of 2,149,844 base pairs, which contains 2,125 predicted protein coding sequences (CDS, 12 rRNA genes, and 45 tRNA genes. Among the protein-encoding CDS are genes involved in resource acquisition and utilization, signal sensing and transduction, carbohydrate metabolism, and defense against host immune response. Potential virulence genes include those encoding adhesins, autolysins, toxins, exoenzymes, and proteases. In addition, two putative prophages and a CRISPR-Cas system were found in the genome, the latter containing a CRISPR locus and four cas genes. Proteomic analysis detected 21 secreted proteins whose expressions were induced by host serum. Five of the serum-responsive proteins were subjected to immunoprotective analysis, which revealed that two of the proteins were highly protective against lethal S. iniae challenge when used as purified recombinant subunit vaccines. Taken together, these results provide an important molecular basis for future study of S. iniae in various aspects, in particular those related to pathogenesis and disease control.

Streptococcus iniae SF1: Complete Genome Sequence, Proteomic Profile, and Immunoprotective Antigens

Science.gov (United States)

Zhang, Bao-cun; Zhang, Jian; Sun, Li

2014-01-01

Streptococcus iniae is a Gram-positive bacterium that is reckoned one of the most severe aquaculture pathogens. It has a broad host range among farmed marine and freshwater fish and can also cause zoonotic infection in humans. Here we report for the first time the complete genome sequence as well as the host factor-induced proteomic profile of a pathogenic S. iniae strain, SF1, a serotype I isolate from diseased fish. SF1 possesses a single chromosome of 2,149,844 base pairs, which contains 2,125 predicted protein coding sequences (CDS), 12 rRNA genes, and 45 tRNA genes. Among the protein-encoding CDS are genes involved in resource acquisition and utilization, signal sensing and transduction, carbohydrate metabolism, and defense against host immune response. Potential virulence genes include those encoding adhesins, autolysins, toxins, exoenzymes, and proteases. In addition, two putative prophages and a CRISPR-Cas system were found in the genome, the latter containing a CRISPR locus and four cas genes. Proteomic analysis detected 21 secreted proteins whose expressions were induced by host serum. Five of the serum-responsive proteins were subjected to immunoprotective analysis, which revealed that two of the proteins were highly protective against lethal S. iniae challenge when used as purified recombinant subunit vaccines. Taken together, these results provide an important molecular basis for future study of S. iniae in various aspects, in particular those related to pathogenesis and disease control. PMID:24621602

Targeted and untargeted high resolution mass approach for a putative profiling of glycosylated simple phenols in hybrid grapes.

Science.gov (United States)

Barnaba, Chiara; Dellacassa, Eduardo; Nicolini, Giorgio; Giacomelli, Mattia; Roman Villegas, Tomas; Nardin, Tiziana; Larcher, Roberto

2017-08-01

Vitis vinifera is one of the most widespread grapevines around the world representing the raw material for high quality wine production. The availability of more resistant interspecific hybrid vine varieties, developed from crosses between Vitis vinifera and other Vitis species, has generated much interest, also due to the low environmental effect of production. However, hybrid grape wine composition and varietal differences between interspecific hybrids have not been well defined, particularly for the simple phenols profile. The dynamic of these phenols in wines, where the glycosylated forms can be transformed into the free ones during winemaking, also raises an increasing health interest by their role as antoxidants in wine consumers. In this work an on-line SPE clean-up device, to reduce matrix interference, was combined with ultra-high liquid chromatography-high resolution mass spectrometry in order to increase understanding of the phenolic composition of hybrid grape varieties. Specifically, the phenolic composition of 4 hybrid grape varieties (red, Cabernet Cantor and Prior; white, Muscaris and Solaris) and 2 European grape varieties (red, Merlot; white, Chardonnay) was investigated, focusing on free and glycosidically bound simple phenols and considering compound distribution in pulp, skin, seeds and wine. Using a targeted approach 53 free simple phenols and 7 glycosidic precursors were quantified with quantification limits ranging from 0.001 to 2mgKg -1 and calibration R 2 of 0.99 for over 86% of compounds. The untargeted approach made it possible to tentatively identify 79 glycosylated precursors of selected free simple phenols in the form of -hexoside (N=30), -pentoside (21), -hexoside-hexoside (17), -hexoside-pentoside (4), -pentoside-hexoside (5) and -pentoside-pentoside (2) derivatives on the basis of accurate mass, isotopic pattern and MS/MS fragmentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

High Resolution Elevation Contours

Data.gov (United States)

Minnesota Department of Natural Resources — This dataset contains contours generated from high resolution data sources such as LiDAR. Generally speaking this data is 2 foot or less contour interval.

Extension of least squares spectral resolution algorithm to high-resolution lipidomics data

Energy Technology Data Exchange (ETDEWEB)

Zeng, Ying-Xu [Department of Chemistry, University of Bergen, PO Box 7803, N-5020 Bergen (Norway); Mjøs, Svein Are, E-mail: svein.mjos@kj.uib.no [Department of Chemistry, University of Bergen, PO Box 7803, N-5020 Bergen (Norway); David, Fabrice P.A. [Bioinformatics and Biostatistics Core Facility, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL) and Swiss Institute of Bioinformatics (SIB), Lausanne (Switzerland); Schmid, Adrien W. [Proteomics Core Facility, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne (Switzerland)

2016-03-31

Lipidomics, which focuses on the global study of molecular lipids in biological systems, has been driven tremendously by technical advances in mass spectrometry (MS) instrumentation, particularly high-resolution MS. This requires powerful computational tools that handle the high-throughput lipidomics data analysis. To address this issue, a novel computational tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. The algorithm features the customized generation of a lipid compound library and mass spectral library, which covers the major lipid classes such as glycerolipids, glycerophospholipids and sphingolipids. Next, the algorithm performs least squares resolution of spectra and chromatograms based on the theoretical isotope distribution of molecular ions, which enables automated identification and quantification of molecular lipid species. Currently, this methodology supports analysis of both high and low resolution MS as well as liquid chromatography-MS (LC-MS) lipidomics data. The flexibility of the methodology allows it to be expanded to support more lipid classes and more data interpretation functions, making it a promising tool in lipidomic data analysis. - Highlights: • A flexible strategy for analyzing MS and LC-MS data of lipid molecules is proposed. • Isotope distribution spectra of theoretically possible compounds were generated. • High resolution MS and LC-MS data were resolved by least squares spectral resolution. • The method proposed compounds that are likely to occur in the analyzed samples. • The proposed compounds matched results from manual interpretation of fragment spectra.

Extension of least squares spectral resolution algorithm to high-resolution lipidomics data

International Nuclear Information System (INIS)

Zeng, Ying-Xu; Mjøs, Svein Are; David, Fabrice P.A.; Schmid, Adrien W.

2016-01-01

Lipidomics, which focuses on the global study of molecular lipids in biological systems, has been driven tremendously by technical advances in mass spectrometry (MS) instrumentation, particularly high-resolution MS. This requires powerful computational tools that handle the high-throughput lipidomics data analysis. To address this issue, a novel computational tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. The algorithm features the customized generation of a lipid compound library and mass spectral library, which covers the major lipid classes such as glycerolipids, glycerophospholipids and sphingolipids. Next, the algorithm performs least squares resolution of spectra and chromatograms based on the theoretical isotope distribution of molecular ions, which enables automated identification and quantification of molecular lipid species. Currently, this methodology supports analysis of both high and low resolution MS as well as liquid chromatography-MS (LC-MS) lipidomics data. The flexibility of the methodology allows it to be expanded to support more lipid classes and more data interpretation functions, making it a promising tool in lipidomic data analysis. - Highlights: • A flexible strategy for analyzing MS and LC-MS data of lipid molecules is proposed. • Isotope distribution spectra of theoretically possible compounds were generated. • High resolution MS and LC-MS data were resolved by least squares spectral resolution. • The method proposed compounds that are likely to occur in the analyzed samples. • The proposed compounds matched results from manual interpretation of fragment spectra.

Broad genomic and transcriptional analysis reveals a highly derived genome in dinoflagellate mitochondria

Directory of Open Access Journals (Sweden)

Keeling Patrick J

2007-09-01

Full Text Available Abstract Background Dinoflagellates comprise an ecologically significant and diverse eukaryotic phylum that is sister to the phylum containing apicomplexan endoparasites. The mitochondrial genome of apicomplexans is uniquely reduced in gene content and size, encoding only three proteins and two ribosomal RNAs (rRNAs within a highly compacted 6 kb DNA. Dinoflagellate mitochondrial genomes have been comparatively poorly studied: limited available data suggest some similarities with apicomplexan mitochondrial genomes but an even more radical type of genomic organization. Here, we investigate structure, content and expression of dinoflagellate mitochondrial genomes. Results From two dinoflagellates, Crypthecodinium cohnii and Karlodinium micrum, we generated over 42 kb of mitochondrial genomic data that indicate a reduced gene content paralleling that of mitochondrial genomes in apicomplexans, i.e., only three protein-encoding genes and at least eight conserved components of the highly fragmented large and small subunit rRNAs. Unlike in apicomplexans, dinoflagellate mitochondrial genes occur in multiple copies, often as gene fragments, and in numerous genomic contexts. Analysis of cDNAs suggests several novel aspects of dinoflagellate mitochondrial gene expression. Polycistronic transcripts were found, standard start codons are absent, and oligoadenylation occurs upstream of stop codons, resulting in the absence of termination codons. Transcripts of at least one gene, cox3, are apparently trans-spliced to generate full-length mRNAs. RNA substitutional editing, a process previously identified for mRNAs in dinoflagellate mitochondria, is also implicated in rRNA expression. Conclusion The dinoflagellate mitochondrial genome shares the same gene complement and fragmentation of rRNA genes with its apicomplexan counterpart. However, it also exhibits several unique characteristics. Most notable are the expansion of gene copy numbers and their arrangements

Ultra-high resolution coded wavefront sensor

KAUST Repository

Wang, Congli

2017-06-08

Wavefront sensors and more general phase retrieval methods have recently attracted a lot of attention in a host of application domains, ranging from astronomy to scientific imaging and microscopy. In this paper, we introduce a new class of sensor, the Coded Wavefront Sensor, which provides high spatio-temporal resolution using a simple masked sensor under white light illumination. Specifically, we demonstrate megapixel spatial resolution and phase accuracy better than 0.1 wavelengths at reconstruction rates of 50 Hz or more, thus opening up many new applications from high-resolution adaptive optics to real-time phase retrieval in microscopy.

Recent Advancements in DNA Damage-Transcription Crosstalk and High-Resolution Mapping of DNA Breaks.

Science.gov (United States)

Vitelli, Valerio; Galbiati, Alessandro; Iannelli, Fabio; Pessina, Fabio; Sharma, Sheetal; d'Adda di Fagagna, Fabrizio

2017-08-31

Until recently, DNA damage arising from physiological DNA metabolism was considered a detrimental by-product for cells. However, an increasing amount of evidence has shown that DNA damage could have a positive role in transcription activation. In particular, DNA damage has been detected in transcriptional elements following different stimuli. These physiological DNA breaks are thought to be instrumental for the correct expression of genomic loci through different mechanisms. In this regard, although a plethora of methods are available to precisely map transcribed regions and transcription start sites, commonly used techniques for mapping DNA breaks lack sufficient resolution and sensitivity to draw a robust correlation between DNA damage generation and transcription. Recently, however, several methods have been developed to map DNA damage at single-nucleotide resolution, thus providing a new set of tools to correlate DNA damage and transcription. Here, we review how DNA damage can positively regulate transcription initiation, the current techniques for mapping DNA breaks at high resolution, and how these techniques can benefit future studies of DNA damage and transcription.

Reconstruction of high temporal resolution Thomson scattering data during a modulated electron cyclotron resonance heating using conditional averaging

International Nuclear Information System (INIS)

Kobayashi, T.; Yoshinuma, M.; Ohdachi, S.; Ida, K.; Itoh, K.; Moon, C.; Yamada, I.; Funaba, H.; Yasuhara, R.; Tsuchiya, H.; Yoshimura, Y.; Igami, H.; Shimozuma, T.; Kubo, S.; Tsujimura, T. I.; Inagaki, S.

2016-01-01

This paper provides a software application of the sampling scope concept for fusion research. The time evolution of Thomson scattering data is reconstructed with a high temporal resolution during a modulated electron cyclotron resonance heating (MECH) phase. The amplitude profile and the delay time profile of the heat pulse propagation are obtained from the reconstructed signal for discharges having on-axis and off-axis MECH depositions. The results are found to be consistent with the MECH deposition.

Reconstruction of high temporal resolution Thomson scattering data during a modulated electron cyclotron resonance heating using conditional averaging

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, T., E-mail: kobayashi.tatsuya@LHD.nifs.ac.jp; Yoshinuma, M.; Ohdachi, S. [National Institute for Fusion Science, Toki 509-5292 (Japan); SOKENDAI (The Graduate University for Advanced Studies), Toki 509-5292 (Japan); Ida, K. [National Institute for Fusion Science, Toki 509-5292 (Japan); SOKENDAI (The Graduate University for Advanced Studies), Toki 509-5292 (Japan); Research Center for Plasma Turbulence, Kyushu University, Kasuga 816-8580 (Japan); Itoh, K. [National Institute for Fusion Science, Toki 509-5292 (Japan); Research Center for Plasma Turbulence, Kyushu University, Kasuga 816-8580 (Japan); Moon, C.; Yamada, I.; Funaba, H.; Yasuhara, R.; Tsuchiya, H.; Yoshimura, Y.; Igami, H.; Shimozuma, T.; Kubo, S.; Tsujimura, T. I. [National Institute for Fusion Science, Toki 509-5292 (Japan); Inagaki, S. [Research Center for Plasma Turbulence, Kyushu University, Kasuga 816-8580 (Japan); Research Institute for Applied Mechanics, Kyushu University, Kasuga 816-8580 (Japan)

2016-04-15

This paper provides a software application of the sampling scope concept for fusion research. The time evolution of Thomson scattering data is reconstructed with a high temporal resolution during a modulated electron cyclotron resonance heating (MECH) phase. The amplitude profile and the delay time profile of the heat pulse propagation are obtained from the reconstructed signal for discharges having on-axis and off-axis MECH depositions. The results are found to be consistent with the MECH deposition.

Comprehensive genome-wide survey, genomic constitution and expression profiling of the NAC transcription factor family in foxtail millet (Setaria italica L..

Directory of Open Access Journals (Sweden)

Swati Puranik

Full Text Available The NAC proteins represent a major plant-specific transcription factor family that has established enormously diverse roles in various plant processes. Aided by the availability of complete genomes, several members of this family have been identified in Arabidopsis, rice, soybean and poplar. However, no comprehensive investigation has been presented for the recently sequenced, naturally stress tolerant crop, Setaria italica (foxtail millet that is famed as a model crop for bioenergy research. In this study, we identified 147 putative NAC domain-encoding genes from foxtail millet by systematic sequence analysis and physically mapped them onto nine chromosomes. Genomic organization suggested that inter-chromosomal duplications may have been responsible for expansion of this gene family in foxtail millet. Phylogenetically, they were arranged into 11 distinct sub-families (I-XI, with duplicated genes fitting into one cluster and possessing conserved motif compositions. Comparative mapping with other grass species revealed some orthologous relationships and chromosomal rearrangements including duplication, inversion and deletion of genes. The evolutionary significance as duplication and divergence of NAC genes based on their amino acid substitution rates was understood. Expression profiling against various stresses and phytohormones provides novel insights into specific and/or overlapping expression patterns of SiNAC genes, which may be responsible for functional divergence among individual members in this crop. Further, we performed structure modeling and molecular simulation of a stress-responsive protein, SiNAC128, proffering an initial framework for understanding its molecular function. Taken together, this genome-wide identification and expression profiling unlocks new avenues for systematic functional analysis of novel NAC gene family candidates which may be applied for improvising stress adaption in plants.

Comprehensive genome-wide survey, genomic constitution and expression profiling of the NAC transcription factor family in foxtail millet (Setaria italica L.).

Science.gov (United States)

Puranik, Swati; Sahu, Pranav Pankaj; Mandal, Sambhu Nath; B, Venkata Suresh; Parida, Swarup Kumar; Prasad, Manoj

2013-01-01

The NAC proteins represent a major plant-specific transcription factor family that has established enormously diverse roles in various plant processes. Aided by the availability of complete genomes, several members of this family have been identified in Arabidopsis, rice, soybean and poplar. However, no comprehensive investigation has been presented for the recently sequenced, naturally stress tolerant crop, Setaria italica (foxtail millet) that is famed as a model crop for bioenergy research. In this study, we identified 147 putative NAC domain-encoding genes from foxtail millet by systematic sequence analysis and physically mapped them onto nine chromosomes. Genomic organization suggested that inter-chromosomal duplications may have been responsible for expansion of this gene family in foxtail millet. Phylogenetically, they were arranged into 11 distinct sub-families (I-XI), with duplicated genes fitting into one cluster and possessing conserved motif compositions. Comparative mapping with other grass species revealed some orthologous relationships and chromosomal rearrangements including duplication, inversion and deletion of genes. The evolutionary significance as duplication and divergence of NAC genes based on their amino acid substitution rates was understood. Expression profiling against various stresses and phytohormones provides novel insights into specific and/or overlapping expression patterns of SiNAC genes, which may be responsible for functional divergence among individual members in this crop. Further, we performed structure modeling and molecular simulation of a stress-responsive protein, SiNAC128, proffering an initial framework for understanding its molecular function. Taken together, this genome-wide identification and expression profiling unlocks new avenues for systematic functional analysis of novel NAC gene family candidates which may be applied for improvising stress adaption in plants.

High resolution data acquisition

Science.gov (United States)

Thornton, Glenn W.; Fuller, Kenneth R.

1993-01-01

A high resolution event interval timing system measures short time intervals such as occur in high energy physics or laser ranging. Timing is provided from a clock (38) pulse train (37) and analog circuitry (44) for generating a triangular wave (46) synchronously with the pulse train (37). The triangular wave (46) has an amplitude and slope functionally related to the time elapsed during each clock pulse in the train. A converter (18, 32) forms a first digital value of the amplitude and slope of the triangle wave at the start of the event interval and a second digital value of the amplitude and slope of the triangle wave at the end of the event interval. A counter (26) counts the clock pulse train (37) during the interval to form a gross event interval time. A computer (52) then combines the gross event interval time and the first and second digital values to output a high resolution value for the event interval.

High resolution time integration for Sn radiation transport

International Nuclear Information System (INIS)

Thoreson, Greg; McClarren, Ryan G.; Chang, Jae H.

2008-01-01

First order, second order and high resolution time discretization schemes are implemented and studied for the S n equations. The high resolution method employs a rate of convergence better than first order, but also suppresses artificial oscillations introduced by second order schemes in hyperbolic differential equations. All three methods were compared for accuracy and convergence rates. For non-absorbing problems, both second order and high resolution converged to the same solution as the first order with better convergence rates. High resolution is more accurate than first order and matches or exceeds the second order method. (authors)

Whole genome DNA methylation: beyond genes silencing

OpenAIRE

Tirado-Magallanes, Roberto; Rebbani, Khadija; Lim, Ricky; Pradhan, Sriharsa; Benoukraf, Touati

2016-01-01

The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation at near base pair level resolution, far beyond that of the kilobase-long canonical CpG islands that initially revealed the biological relevance of this covalent DNA modification. The latest high-resolution studies have revealed a role for very punctual DNA methylation in chromatin plasticity, gene regulation and splicing. Here, we aim to outline the ...

Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma.

Directory of Open Access Journals (Sweden)

Derek J Nancarrow

Full Text Available Esophageal adenocarcinoma (EAC has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE, which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2 designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1 and xenobiotic (AKR1C2, AKR1B10 defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.

Genomic research in Eucalyptus.

Science.gov (United States)

Poke, Fiona S; Vaillancourt, René E; Potts, Brad M; Reid, James B

2005-09-01

Eucalyptus L'Hérit. is a genus comprised of more than 700 species that is of vital importance ecologically to Australia and to the forestry industry world-wide, being grown in plantations for the production of solid wood products as well as pulp for paper. With the sequencing of the genomes of Arabidopsis thaliana and Oryza sativa and the recent completion of the first tree genome sequence, Populus trichocarpa, attention has turned to the current status of genomic research in Eucalyptus. For several eucalypt species, large segregating families have been established, high-resolution genetic maps constructed and large EST databases generated. Collaborative efforts have been initiated for the integration of diverse genomic projects and will provide the framework for future research including exploiting the sequence of the entire eucalypt genome which is currently being sequenced. This review summarises the current position of genomic research in Eucalyptus and discusses the direction of future research.

Structure of high-resolution NMR spectra

CERN Document Server

Corio, PL

2012-01-01

Structure of High-Resolution NMR Spectra provides the principles, theories, and mathematical and physical concepts of high-resolution nuclear magnetic resonance spectra.The book presents the elementary theory of magnetic resonance; the quantum mechanical theory of angular momentum; the general theory of steady state spectra; and multiple quantum transitions, double resonance and spin echo experiments.Physicists, chemists, and researchers will find the book a valuable reference text.

Snowpack spatial and temporal variability assessment using SMP high-resolution penetrometer

Science.gov (United States)

Komarov, Anton; Seliverstov, Yuriy; Sokratov, Sergey; Grebennikov, Pavel

2017-04-01

This research is focused on study of spatial and temporal variability of structure and characteristics of snowpack, quick identification of layers based on hardness and dispersion values received from snow micro penetrometer (SMP). We also discuss the detection of weak layers and definition of their parameters in non-alpine terrain. As long as it is the first SMP tool available in Russia, our intent is to test it in different climate and weather conditions. During two separate snowpack studies in plain and mountain landscapes, we derived density and grain size profiles by comparing snow density and grain size from snowpits and SMP measurements. The first case study was MSU meteorological observatory test site in Moscow. SMP data was obtained by 6 consecutive measurements along 10 m transects with a horizontal resolution of approximately 50 cm. The detailed description of snowpack structure, density, grain size, air and snow temperature was also performed. By comparing this information, the detailed scheme of snowpack evolution was created. The second case study was in Khibiny mountains. One 10-meter-long transect was made. SMP, density, grain size and snow temperature data was obtained with horizontal resolution of approximately 50 cm. The high-definition profile of snowpack density variation was acquired using received data. The analysis of data reveals high spatial and temporal variability in snow density and layer structure in both horizontal and vertical dimensions. It indicates that the spatial variability is exhibiting similar spatial patterns as surface topology. This suggests a strong influence from such factors as wind and liquid water pressure on the temporal and spatial evolution of snow structure. It was also defined, that spatial variation of snowpack characteristics is substantial even within homogeneous plain landscape, while in high-latitude mountain regions it grows significantly.

High-resolution multi-slice PET

International Nuclear Information System (INIS)

Yasillo, N.J.; Chintu Chen; Ordonez, C.E.; Kapp, O.H.; Sosnowski, J.; Beck, R.N.

1992-01-01

This report evaluates the progress to test the feasibility and to initiate the design of a high resolution multi-slice PET system. The following specific areas were evaluated: detector development and testing; electronics configuration and design; mechanical design; and system simulation. The design and construction of a multiple-slice, high-resolution positron tomograph will provide substantial improvements in the accuracy and reproducibility of measurements of the distribution of activity concentrations in the brain. The range of functional brain research and our understanding of local brain function will be greatly extended when the development of this instrumentation is completed

High resolution NMR spectroscopy of synthetic polymers in bulk

International Nuclear Information System (INIS)

Komorski, R.A.

1986-01-01

The contents of this book are: Overview of high-resolution NMR of solid polymers; High-resolution NMR of glassy amorphous polymers; Carbon-13 solid-state NMR of semicrystalline polymers; Conformational analysis of polymers of solid-state NMR; High-resolution NMR studies of oriented polymers; High-resolution solid-state NMR of protons in polymers; and Deuterium NMR of solid polymers. This work brings together the various approaches for high-resolution NMR studies of bulk polymers into one volume. Heavy emphasis is, of course, given to 13C NMR studies both above and below Tg. Standard high-power pulse and wide-line techniques are not covered

Genomic analyses inform on migration events during the peopling of Eurasia

OpenAIRE

Pagani, L; Lawson, DJ; Jagoda, E; Mörseburg, A; Eriksson, A; Mitt, M; Clemente, F; Hudjashov, G; Degiorgio, M; Saag, L; Wall, JD; Cardona, A; Mägi, R; Sayres, MAW; Kaewert, S

2016-01-01

© 2016 Macmillan Publishers Limited, part of Springer Nature. High-Coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome D...

Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs

Directory of Open Access Journals (Sweden)

Ringnér Markus

2008-07-01

Full Text Available Abstract Background Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors. Methods 32 K tiling microarray-based comparative genomic hybridization (aCGH was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters. Results Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 × 10-5 unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29 displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses. Conclusion Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and

Extended-Range High-Resolution Dynamical Downscaling over a Continental-Scale Domain

Science.gov (United States)

Husain, S. Z.; Separovic, L.; Yu, W.; Fernig, D.

2014-12-01

High-resolution mesoscale simulations, when applied for downscaling meteorological fields over large spatial domains and for extended time periods, can provide valuable information for many practical application scenarios including the weather-dependent renewable energy industry. In the present study, a strategy has been proposed to dynamically downscale coarse-resolution meteorological fields from Environment Canada's regional analyses for a period of multiple years over the entire Canadian territory. The study demonstrates that a continuous mesoscale simulation over the entire domain is the most suitable approach in this regard. Large-scale deviations in the different meteorological fields pose the biggest challenge for extended-range simulations over continental scale domains, and the enforcement of the lateral boundary conditions is not sufficient to restrict such deviations. A scheme has therefore been developed to spectrally nudge the simulated high-resolution meteorological fields at the different model vertical levels towards those embedded in the coarse-resolution driving fields derived from the regional analyses. A series of experiments were carried out to determine the optimal nudging strategy including the appropriate nudging length scales, nudging vertical profile and temporal relaxation. A forcing strategy based on grid nudging of the different surface fields, including surface temperature, soil-moisture, and snow conditions, towards their expected values obtained from a high-resolution offline surface scheme was also devised to limit any considerable deviation in the evolving surface fields due to extended-range temporal integrations. The study shows that ensuring large-scale atmospheric similarities helps to deliver near-surface statistical scores for temperature, dew point temperature and horizontal wind speed that are better or comparable to the operational regional forecasts issued by Environment Canada. Furthermore, the meteorological fields

Development of a high-resolution Thomson scattering system for plasma interactions with molten salt (FLiNaK)

Energy Technology Data Exchange (ETDEWEB)

Lee, K. Y. [National Fusion Research Institute, Gunsan (Korea, Republic of)

2014-10-15

A high-resolution Thomson scattering system is presently being developed to measure the electron temperature and density profile during plasma interaction with molten salt. The system uses a 20-Hz Nd:YAG laser operating at the second harmonic (532 nm). The collection lens, having a 1:10 magnification ratio, measures 63 points along the 10-cm profile. The scattered light is transmitted by using an optical-fiber bundle, and is analyzed with a triple-grating spectrometer to further reduce stray light. Its spectral resolution is expected to be 0.03 nm. An intensified charge-coupled device (ICCD) camera consisting of a gated image intensifier coupled to the CCD camera is used to record the spectral distribution of the scattered light. An additional feature of operating the ICCD camera at 40-Hz to record the background signal is incorporated.

High resolution integral holography using Fourier ptychographic approach.

Science.gov (United States)

Li, Zhaohui; Zhang, Jianqi; Wang, Xiaorui; Liu, Delian

2014-12-29

An innovative approach is proposed for calculating high resolution computer generated integral holograms by using the Fourier Ptychographic (FP) algorithm. The approach initializes a high resolution complex hologram with a random guess, and then stitches together low resolution multi-view images, synthesized from the elemental images captured by integral imaging (II), to recover the high resolution hologram through an iterative retrieval with FP constrains. This paper begins with an analysis of the principle of hologram synthesis from multi-projections, followed by an accurate determination of the constrains required in the Fourier ptychographic integral-holography (FPIH). Next, the procedure of the approach is described in detail. Finally, optical reconstructions are performed and the results are demonstrated. Theoretical analysis and experiments show that our proposed approach can reconstruct 3D scenes with high resolution.

Multi-pinhole collimator design for small-object imaging with SiliSPECT: a high-resolution SPECT

International Nuclear Information System (INIS)

Shokouhi, S; Peterson, T E; Metzler, S D; Wilson, D W

2009-01-01

We have designed a multi-pinhole collimator for a dual-headed, stationary SPECT system that incorporates high-resolution silicon double-sided strip detectors. The compact camera design of our system enables imaging at source-collimator distances between 20 and 30 mm. Our analytical calculations show that using knife-edge pinholes with small-opening angles or cylindrically shaped pinholes in a focused, multi-pinhole configuration in combination with this camera geometry can generate narrow sensitivity profiles across the field of view that can be useful for imaging small objects at high sensitivity and resolution. The current prototype system uses two collimators each containing 127 cylindrically shaped pinholes that are focused toward a target volume. Our goal is imaging objects such as a mouse brain, which could find potential applications in molecular imaging.

Assembly of highly repetitive genomes using short reads: the genome of discrete typing unit III Trypanosoma cruzi strain 231.

Science.gov (United States)

Baptista, Rodrigo P; Reis-Cunha, Joao Luis; DeBarry, Jeremy D; Chiari, Egler; Kissinger, Jessica C; Bartholomeu, Daniella C; Macedo, Andrea M

2018-02-14

Next-generation sequencing (NGS) methods are low-cost high-throughput technologies that produce thousands to millions of sequence reads. Despite the high number of raw sequence reads, their short length, relative to Sanger, PacBio or Nanopore reads, complicates the assembly of genomic repeats. Many genome tools are available, but the assembly of highly repetitive genome sequences using only NGS short reads remains challenging. Genome assembly of organisms responsible for important neglected diseases such as Trypanosoma cruzi, the aetiological agent of Chagas disease, is known to be challenging because of their repetitive nature. Only three of six recognized discrete typing units (DTUs) of the parasite have their draft genomes published and therefore genome evolution analyses in the taxon are limited. In this study, we developed a computational workflow to assemble highly repetitive genomes via a combination of de novo and reference-based assembly strategies to better overcome the intrinsic limitations of each, based on Illumina reads. The highly repetitive genome of the human-infecting parasite T. cruzi 231 strain was used as a test subject. The combined-assembly approach shown in this study benefits from the reference-based assembly ability to resolve highly repetitive sequences and from the de novo capacity to assemble genome-specific regions, improving the quality of the assembly. The acceptable confidence obtained by analyzing our results showed that our combined approach is an attractive option to assemble highly repetitive genomes with NGS short reads. Phylogenomic analysis including the 231 strain, the first representative of DTU III whose genome was sequenced, was also performed and provides new insights into T. cruzi genome evolution.

High-spatial resolution and high-spectral resolution detector for use in the measurement of solar flare hard x rays

International Nuclear Information System (INIS)

Desai, U.D.; Orwig, L.E.

1988-01-01

In the areas of high spatial resolution, the evaluation of a hard X-ray detector with 65 micron spatial resolution for operation in the energy range from 30 to 400 keV is proposed. The basic detector is a thick large-area scintillator faceplate, composed of a matrix of high-density scintillating glass fibers, attached to a proximity type image intensifier tube with a resistive-anode digital readout system. Such a detector, combined with a coded-aperture mask, would be ideal for use as a modest-sized hard X-ray imaging instrument up to X-ray energies as high as several hundred keV. As an integral part of this study it was also proposed that several techniques be critically evaluated for X-ray image coding which could be used with this detector. In the area of high spectral resolution, it is proposed to evaluate two different types of detectors for use as X-ray spectrometers for solar flares: planar silicon detectors and high-purity germanium detectors (HPGe). Instruments utilizing these high-spatial-resolution detectors for hard X-ray imaging measurements from 30 to 400 keV and high-spectral-resolution detectors for measurements over a similar energy range would be ideally suited for making crucial solar flare observations during the upcoming maximum in the solar cycle

Comparative high-resolution mapping of the wax inhibitors Iw1 and Iw2 in hexaploid wheat.

Directory of Open Access Journals (Sweden)

Haibin Wu

Full Text Available The wax (glaucousness on wheat leaves and stems is mainly controlled by two sets of genes: glaucousness loci (W1 and W2 and non-glaucousness loci (Iw1 and Iw2. The non-glaucousness (Iw loci act as inhibitors of the glaucousness loci (W. High-resolution comparative genetic linkage maps of the wax inhibitors Iw1 originating from Triticum dicoccoides, and Iw2 from Aegilops tauschii were developed by comparative genomics analyses of Brachypodium, sorghum and rice genomic sequences corresponding to the syntenic regions of the Iw loci in wheat. Eleven Iw1 and eight Iw2 linked EST markers were developed and mapped to linkage maps on the distal regions of chromosomes 2BS and 2DS, respectively. The Iw1 locus mapped within a 0.96 cM interval flanked by the BE498358 and CA499581 EST markers that are collinear with 122 kb, 202 kb, and 466 kb genomic regions in the Brachypodium 5S chromosome, the sorghum 6S chromosome and the rice 4S chromosome, respectively. The Iw2 locus was located in a 4.1 to 5.4-cM interval in chromosome 2DS that is flanked by the CJ886319 and CJ519831 EST markers, and this region is collinear with a 2.3 cM region spanning the Iw1 locus on chromosome 2BS. Both Iw1 and Iw2 co-segregated with the BF474014 and CJ876545 EST markers, indicating they are most likely orthologs on 2BS and 2DS. These high-resolution maps can serve as a framework for chromosome landing, physical mapping and map-based cloning of the wax inhibitors in wheat.

High-Resolution Gas Metering and Nonintrusive Appliance Load Monitoring System

Science.gov (United States)

Tewolde, Mahder

This thesis deals with design and implementation of a high-resolution metering system for residential natural gas meters. Detailed experimental measurements are performed on the meter to characterize and understand its measurement properties. Results from these experiments are used to develop a simple, fast and accurate technique to non-intrusively monitor the gas consumption of individual appliances in homes by resolving small amounts of gas usage. The technique is applied on an existing meter retrofitted with a module that includes a high-resolution encoder to collect gas flow data and a microprocessor to analyze and identify appliance load profiles. This approach provides a number of appealing features including low cost, easy installation and integration with automated meter reading (AMR) systems. The application of this method to residential gas meters currently deployed is also given. This is done by performing a load simulation on realistic gas loads with the aim of identifying the necessary parameters that minimize the cost and complexity of the mechanical encoder module. The primary benefits of the system are efficiency analysis, appliance health monitoring and real-time customer feedback of gas usage. Additional benefits of include the ability to detect very small leaks and theft. This system has the potential for wide scale market adoption.

Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia--a comparative study of four differently designed, high resolution microarray platforms

DEFF Research Database (Denmark)

Gunnarsson, R.; Staaf, J.; Jansson, M.

2008-01-01

Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K)...

High resolution photoelectron spectroscopy

International Nuclear Information System (INIS)

Arko, A.J.

1988-01-01

Photoelectron Spectroscopy (PES) covers a very broad range of measurements, disciplines, and interests. As the next generation light source, the FEL will result in improvements over the undulator that are larger than the undulater improvements over bending magnets. The combination of high flux and high inherent resolution will result in several orders of magnitude gain in signal to noise over measurements using synchrotron-based undulators. The latter still require monochromators. Their resolution is invariably strongly energy-dependent so that in the regions of interest for many experiments (h upsilon > 100 eV) they will not have a resolving power much over 1000. In order to study some of the interesting phenomena in actinides (heavy fermions e.g.) one would need resolving powers of 10 4 to 10 5 . These values are only reachable with the FEL

DETECTING LOW-LEVEL SYNTHESIS IMPURITIES IN MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES USING LIQUID CHROMATOGRAPHY – HIGH RESOLUTION MASS SPECTROMETRY

Science.gov (United States)

Nikcevic, Irena; Wyrzykiewicz, Tadeusz K.; Limbach, Patrick A.

2010-01-01

Summary An LC-MS method based on the use of high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTIRCMS) for profiling oligonucleotides synthesis impurities is described. Oligonucleotide phosphorothioatediesters (phosphorothioate oligonucleotides), in which one of the non-bridging oxygen atoms at each phosphorus center is replaced by a sulfur atom, are now one of the most popular oligonucleotide modifications due to their ease of chemical synthesis and advantageous pharmacokinetic properties. Despite significant progress in the solid-phase oligomerization chemistry used in the manufacturing of these oligonucleotides, multiple classes of low-level impurities always accompany synthetic oligonucleotides. Liquid chromatography-mass spectrometry has emerged as a powerful technique for the identification of these synthesis impurities. However, impurity profiling, where the entire complement of low-level synthetic impurities is identified in a single analysis, is more challenging. Here we present an LC-MS method based the use of high resolution-mass spectrometry, specifically Fourier transform ion cyclotron resonance mass spectrometry (FTIRCMS or FTMS). The optimal LC-FTMS conditions, including the stationary phase and mobile phases for the separation and identification of phosphorothioate oligonucleotides, were found. The characteristics of FTMS enable charge state determination from single m/z values of low-level impurities. Charge state information then enables more accurate modeling of the detected isotopic distribution for identification of the chemical composition of the detected impurity. Using this approach, a number of phosphorothioate impurities can be detected by LC-FTMS including failure sequences carrying 3′-terminal phosphate monoester and 3′-terminal phosphorothioate monoester, incomplete backbone sulfurization and desulfurization products, high molecular weight impurities, and chloral, isobutyryl, and N3 (2-cyanoethyl) adducts

Extended-range high-resolution dynamical downscaling over a continental-scale spatial domain with atmospheric and surface nudging

Science.gov (United States)

Husain, S. Z.; Separovic, L.; Yu, W.; Fernig, D.

2014-12-01

Extended-range high-resolution mesoscale simulations with limited-area atmospheric models when applied to downscale regional analysis fields over large spatial domains can provide valuable information for many applications including the weather-dependent renewable energy industry. Long-term simulations over a continental-scale spatial domain, however, require mechanisms to control the large-scale deviations in the high-resolution simulated fields from the coarse-resolution driving fields. As enforcement of the lateral boundary conditions is insufficient to restrict such deviations, large scales in the simulated high-resolution meteorological fields are therefore spectrally nudged toward the driving fields. Different spectral nudging approaches, including the appropriate nudging length scales as well as the vertical profiles and temporal relaxations for nudging, have been investigated to propose an optimal nudging strategy. Impacts of time-varying nudging and generation of hourly analysis estimates are explored to circumvent problems arising from the coarse temporal resolution of the regional analysis fields. Although controlling the evolution of the atmospheric large scales generally improves the outputs of high-resolution mesoscale simulations within the surface layer, the prognostically evolving surface fields can nevertheless deviate from their expected values leading to significant inaccuracies in the predicted surface layer meteorology. A forcing strategy based on grid nudging of the different surface fields, including surface temperature, soil moisture, and snow conditions, toward their expected values obtained from a high-resolution offline surface scheme is therefore proposed to limit any considerable deviation. Finally, wind speed and temperature at wind turbine hub height predicted by different spectrally nudged extended-range simulations are compared against observations to demonstrate possible improvements achievable using higher spatiotemporal

Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling.

Science.gov (United States)

Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute; Blake, Jonathon; Schwager, Christian; Ansorge, Wilhelm; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

2004-07-15

Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.

High resolution aquifer characterization using crosshole GPR full-waveform tomography

Science.gov (United States)

Gueting, N.; Vienken, T.; Klotzsche, A.; Van Der Kruk, J.; Vanderborght, J.; Caers, J.; Vereecken, H.; Englert, A.

2016-12-01

Limited knowledge about the spatial distribution of aquifer properties typically constrains our ability to predict subsurface flow and transport. Here, we investigate the value of using high resolution full-waveform inversion of cross-borehole ground penetrating radar (GPR) data for aquifer characterization. By stitching together GPR tomograms from multiple adjacent crosshole planes, we are able to image, with a decimeter scale resolution, the dielectric permittivity and electrical conductivity of an alluvial aquifer along cross-sections of 50 m length and 10 m depth. A logistic regression model is employed to predict the spatial distribution of lithological facies on the basis of the GPR results. Vertical profiles of porosity and hydraulic conductivity from direct-push, flowmeter and grain size data suggest that the GPR predicted facies classification is meaningful with regard to porosity and hydraulic conductivity, even though the distributions of individual facies show some overlap and the absolute hydraulic conductivities from the different methods (direct-push, flowmeter, grain size) differ up to approximately one order of magnitude. Comparison of the GPR predicted facies architecture with tracer test data suggests that the plume splitting observed in a tracer experiment was caused by a hydraulically low-conductive sand layer with a thickness of only a few decimeters. Because this sand layer is identified by GPR full-waveform inversion but not by conventional GPR ray-based inversion we conclude that the improvement in spatial resolution due to full-waveform inversion is crucial to detect small-scale aquifer structures that are highly relevant for solute transport.

The sea lamprey meiotic map improves resolution of ancient vertebrate genome duplications.

Science.gov (United States)

Smith, Jeramiah J; Keinath, Melissa C

2015-08-01

It is generally accepted that many genes present in vertebrate genomes owe their origin to two whole-genome duplications that occurred deep in the ancestry of the vertebrate lineage. However, details regarding the timing and outcome of these duplications are not well resolved. We present high-density meiotic and comparative genomic maps for the sea lamprey (Petromyzon marinus), a representative of an ancient lineage that diverged from all other vertebrates ∼550 million years ago. Linkage analyses yielded a total of 95 linkage groups, similar to the estimated number of germline chromosomes (1n ∼ 99), spanning a total of 5570.25 cM. Comparative mapping data yield strong support for the hypothesis that a single whole-genome duplication occurred in the basal vertebrate lineage, but do not strongly support a hypothetical second event. Rather, these comparative maps reveal several evolutionarily independent segmental duplications occurring over the last 600+ million years of chordate evolution. This refined history of vertebrate genome duplication should permit more precise investigations of vertebrate evolution. © 2015 Smith and Keinath; Published by Cold Spring Harbor Laboratory Press.