Thermo-Mechanical Fatigue Crack Growth of RR1000

PubMed Central

Pretty, Christopher John; Whitaker, Mark Thomas; Williams, Steve John

2017-01-01

Non-isothermal conditions during flight cycles have long led to the requirement for thermo-mechanical fatigue (TMF) evaluation of aerospace materials. However, the increased temperatures within the gas turbine engine have meant that the requirements for TMF testing now extend to disc alloys along with blade materials. As such, fatigue crack growth rates are required to be evaluated under non-isothermal conditions along with the development of a detailed understanding of related failure mechanisms. In the current work, a TMF crack growth testing method has been developed utilising induction heating and direct current potential drop techniques for polycrystalline nickel-based superalloys, such as RR1000. Results have shown that in-phase (IP) testing produces accelerated crack growth rates compared with out-of-phase (OOP) due to increased temperature at peak stress and therefore increased time dependent crack growth. The ordering of the crack growth rates is supported by detailed fractographic analysis which shows intergranular crack growth in IP test specimens, and transgranular crack growth in 90° OOP and 180° OOP tests. Isothermal tests have also been carried out for comparison of crack growth rates at the point of peak stress in the TMF cycles. PMID:28772394

BCX4430, a novel nucleoside analog, effectively treats yellow fever in a Hamster model.

PubMed

Julander, Justin G; Bantia, Shanta; Taubenheim, Brian R; Minning, Dena M; Kotian, Pravin; Morrey, John D; Smee, Donald F; Sheridan, William P; Babu, Yarlagadda S

2014-11-01

No effective antiviral therapies are currently available to treat disease after infection with yellow fever virus (YFV). A Syrian golden hamster model of yellow fever (YF) was used to characterize the effect of treatment with BCX4430, a novel adenosine nucleoside analog. Significant improvement in survival was observed after treatment with BCX4430 at 4 mg/kg of body weight per day dosed intraperitoneally (i.p.) twice daily (BID). Treatment with BCX4430 at 12.5 mg/kg/day administered i.p. BID for 7 days offered complete protection from mortality and also resulted in significant improvement of other YF disease parameters, including weight loss, serum alanine aminotransferase levels (6 days postinfection [dpi]), and viremia (4 dpi). In uninfected hamsters, BCX4430 at 200 mg/kg/day administered i.p. BID for 7 days was well tolerated and did not result in mortality or weight loss, suggesting a potentially wide therapeutic index. Treatment with BCX4430 at 12 mg/kg/day i.p. remained effective when administered once daily and for only 4 days. Moreover, BCX4430 dosed at 200 mg/kg/day i.p. BID for 7 days effectively treated YF, even when treatment was delayed up to 4 days after virus challenge, corresponding with peak viral titers in the liver and serum. BCX4430 treatment did not preclude a protective antibody response, as higher neutralizing antibody (nAb) concentrations corresponded with increasing delays of treatment initiation, and greater nAb responses resulted in the protection of animals from a secondary challenge with YFV. In summary, BCX4430 is highly active in a hamster model of YF, even when treatment is initiated at the peak of viral replication. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Veff Scaling of Te and ne Measurements During Local Helicity Injection on the Pegasus Toroidal Experiment

NASA Astrophysics Data System (ADS)

Bodner, G. M.; Bongard, M. W.; Fonck, R. J.; Perry, J. M.; Reusch, J. A.; Rodriguez Sanchez, C.

2017-10-01

Understanding the electron confinement of local helicity injection (LHI) is critical in order to evaluate its scalability as a startup technique to MA-class devices. Electron confinement in the Pegasus Toroidal Experiment is investigated using multi-point Thomson scattering (TS). The Pegasus TS system utilizes a set of high-throughput transmission gratings and intensified CCDs to measure Te and ne profiles. Previous TS measurements indicated peaked Te profiles 120 eV in outboard injector discharges characterized by strong inductive drive and low LHI drive. Injectors designed to have dominant non-inductive drive have recently been installed in the divertor region of Pegasus to understand the relationship between effective drive voltage, Veff, and plasma performance. At low Veff and reduced plasma current, Ip 60 kA, TS measurements reveal a flat Te profile 50 eV, with a peaked ne profile 1 ×1019 m-3, resulting in a slightly peaked pe profile. As current drive is increased, the Te profiles become hollow with a core Te 50 eV and an edge Te 120 -150 eV. These hollow profiles appear after the start of the Ip flattop and are sustained until the discharge terminates. The ne profiles drop in magnitude to < 1 ×1019 m-3 but remain somewhat peaked. Initial results suggest a weak scaling between input power and core Te. Additional studies are planned to identify the mechanisms behind the anomalous profile features. Work supported by US DOE Grant DE-FG02-96ER54375.

Accounting for GC-content bias reduces systematic errors and batch effects in ChIP-seq data.

PubMed

Teng, Mingxiang; Irizarry, Rafael A

2017-11-01

The main application of ChIP-seq technology is the detection of genomic regions that bind to a protein of interest. A large part of functional genomics' public catalogs is based on ChIP-seq data. These catalogs rely on peak calling algorithms that infer protein-binding sites by detecting genomic regions associated with more mapped reads (coverage) than expected by chance, as a result of the experimental protocol's lack of perfect specificity. We find that GC-content bias accounts for substantial variability in the observed coverage for ChIP-seq experiments and that this variability leads to false-positive peak calls. More concerning is that the GC effect varies across experiments, with the effect strong enough to result in a substantial number of peaks called differently when different laboratories perform experiments on the same cell line. However, accounting for GC content bias in ChIP-seq is challenging because the binding sites of interest tend to be more common in high GC-content regions, which confounds real biological signals with unwanted variability. To account for this challenge, we introduce a statistical approach that accounts for GC effects on both nonspecific noise and signal induced by the binding site. The method can be used to account for this bias in binding quantification as well to improve existing peak calling algorithms. We use this approach to show a reduction in false-positive peaks as well as improved consistency across laboratories. © 2017 Teng and Irizarry; Published by Cold Spring Harbor Laboratory Press.

Modeling of divertor power footprint widths on EAST by SOLPS5.0/B2.5-Eirene

NASA Astrophysics Data System (ADS)

Deng, Guozhong; Liu, Xiaoju; Wang, Liang; Liu, Shaocheng; Xu, Jichan; Feng, Wei; Liu, Jianbin; Liu, Huan; Gao, Xiang

2017-04-01

The edge plasma code package SOLPS5.0 is employed to simulate the divertor power footprint widths of the experimental advanced superconducting tokamak (EAST) L-mode and ELM-free H-mode plasmas. The divertor power footprint widths, which consist of the scrape-off layer (SOL) width λ q and heat spreading S, are important physical parameters for edge plasmas. In this work, a plasma current scan is implemented in the simulation to obtain the dependence of the divertor power footprint width on the plasma current I p. Strong inverse scaling of the SOL width with I p has been achieved for both L-mode and H-mode plasmas in the forms of {λ }q,{{L}\\text-\\text{mode}}=4.98× {I}{{p}}-0.68 and {λ }q,{{H}\\text-\\text{mode}}=1.86× {I}{{p}}-1.08. Similar trends have also been demonstrated in the study of heat spreading with {S}{{L}\\text-\\text{mode}}=1.95× {I}{{p}}-0.542 and {S}{{H}\\text-\\text{mode}}=0.756× {I}{{p}}-0.872. In addition, studies on divertor peak heat load and the magnetic flux expansion factor show that both of them are proportional to plasma current. The simulation work here can act as a way to explore the power footprint widths of future tokamak fusion devices such as ITER and the China Fusion Engineering Test Reactor (CFETR).

PeakRanger: A cloud-enabled peak caller for ChIP-seq data

PubMed Central

2011-01-01

Background Chromatin immunoprecipitation (ChIP), coupled with massively parallel short-read sequencing (seq) is used to probe chromatin dynamics. Although there are many algorithms to call peaks from ChIP-seq datasets, most are tuned either to handle punctate sites, such as transcriptional factor binding sites, or broad regions, such as histone modification marks; few can do both. Other algorithms are limited in their configurability, performance on large data sets, and ability to distinguish closely-spaced peaks. Results In this paper, we introduce PeakRanger, a peak caller software package that works equally well on punctate and broad sites, can resolve closely-spaced peaks, has excellent performance, and is easily customized. In addition, PeakRanger can be run in a parallel cloud computing environment to obtain extremely high performance on very large data sets. We present a series of benchmarks to evaluate PeakRanger against 10 other peak callers, and demonstrate the performance of PeakRanger on both real and synthetic data sets. We also present real world usages of PeakRanger, including peak-calling in the modENCODE project. Conclusions Compared to other peak callers tested, PeakRanger offers improved resolution in distinguishing extremely closely-spaced peaks. PeakRanger has above-average spatial accuracy in terms of identifying the precise location of binding events. PeakRanger also has excellent sensitivity and specificity in all benchmarks evaluated. In addition, PeakRanger offers significant improvements in run time when running on a single processor system, and very marked improvements when allowed to take advantage of the MapReduce parallel environment offered by a cloud computing resource. PeakRanger can be downloaded at the official site of modENCODE project: http://www.modencode.org/software/ranger/ PMID:21554709

GenoGAM: genome-wide generalized additive models for ChIP-Seq analysis.

PubMed

Stricker, Georg; Engelhardt, Alexander; Schulz, Daniel; Schmid, Matthias; Tresch, Achim; Gagneur, Julien

2017-08-01

Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) is a widely used approach to study protein-DNA interactions. Often, the quantities of interest are the differential occupancies relative to controls, between genetic backgrounds, treatments, or combinations thereof. Current methods for differential occupancy of ChIP-Seq data rely however on binning or sliding window techniques, for which the choice of the window and bin sizes are subjective. Here, we present GenoGAM (Genome-wide Generalized Additive Model), which brings the well-established and flexible generalized additive models framework to genomic applications using a data parallelism strategy. We model ChIP-Seq read count frequencies as products of smooth functions along chromosomes. Smoothing parameters are objectively estimated from the data by cross-validation, eliminating ad hoc binning and windowing needed by current approaches. GenoGAM provides base-level and region-level significance testing for full factorial designs. Application to a ChIP-Seq dataset in yeast showed increased sensitivity over existing differential occupancy methods while controlling for type I error rate. By analyzing a set of DNA methylation data and illustrating an extension to a peak caller, we further demonstrate the potential of GenoGAM as a generic statistical modeling tool for genome-wide assays. Software is available from Bioconductor: https://www.bioconductor.org/packages/release/bioc/html/GenoGAM.html . gagneur@in.tum.de. Supplementary information is available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Comparison of the KSC-ER Cloud-to-Ground Lightning Surveillance System (CGLSS) and the U.S. National Lightning Detection Network(TradeMark)(NLDN)

NASA Technical Reports Server (NTRS)

Ward, Jennifer G.; Cummins, Kenneth L.; Krider, E. Philip

2007-01-01

The NASA Kennedy Space Center (KSC) and Air Force Eastern Range (ER) use data from two cloud-to-ground lightning detection networks, CGLSS and NLDN, during ground and launch operations at the KSC-ER. For these applications, it is very important to understand the location accuracy and detection efficiency of each network near the KSC-ER. If a cloud-to-ground (CG) lightning strike is missed or mis-located by even a small amount, the result could have significant safety implications, require expensive retests, or create unnecessary delays or scrubs in launches. Therefore, it is important to understand the performance of each lightning detection system in considerable detail. To evaluate recent upgrades in the CGLSS sensors in 2000 and the entire NLDN in 2002- 2003, we have compared. measurements provided by these independent networks in the summers of 2005 and 2006. Our analyses have focused on the fraction of first strokes reported individually and in-common by each network (flash detection efficiency), the spatial separation between the strike points reported by both networks (relative location accuracy), and the values of the estimated peak current, Ip, reported by each network. The results within 100 km of the KSC-ER show that the networks produce very similar values of Ip (except for a small scaling difference) and that the relative location accuracy is consistent with model estimates that give median values of 200-300m for the CGLSS and 600-700m for the NLDN in the region of the KSC-ER. Because of differences in the network geometries and sensor gains, the NLDN does not report 10-20% of the flashes that have a low Ip (2 kA < |Ip| < 16 kA), both networks report 99 % of the flashes that have intermediate values of Ip (16< |Ip| < 50 kA), and the CGLSS fails to report 20-30% of the high-current events (|Ip| >=0 kA).

D-peaks: a visual tool to display ChIP-seq peaks along the genome.

PubMed

Brohée, Sylvain; Bontempi, Gianluca

2012-01-01

ChIP-sequencing is a method of choice to localize the positions of protein binding sites on DNA on a whole genomic scale. The deciphering of the sequencing data produced by this novel technique is challenging and it is achieved by their rigorous interpretation using dedicated tools and adapted visualization programs. Here, we present a bioinformatics tool (D-peaks) that adds several possibilities (including, user-friendliness, high-quality, relative position with respect to the genomic features) to the well-known visualization browsers or databases already existing. D-peaks is directly available through its web interface http://rsat.ulb.ac.be/dpeaks/ as well as a command line tool.

Optimizing ChIP-seq peak detectors using visual labels and supervised machine learning

PubMed Central

Goerner-Potvin, Patricia; Morin, Andreanne; Shao, Xiaojian; Pastinen, Tomi

2017-01-01

Motivation: Many peak detection algorithms have been proposed for ChIP-seq data analysis, but it is not obvious which algorithm and what parameters are optimal for any given dataset. In contrast, regions with and without obvious peaks can be easily labeled by visual inspection of aligned read counts in a genome browser. We propose a supervised machine learning approach for ChIP-seq data analysis, using labels that encode qualitative judgments about which genomic regions contain or do not contain peaks. The main idea is to manually label a small subset of the genome, and then learn a model that makes consistent peak predictions on the rest of the genome. Results: We created 7 new histone mark datasets with 12 826 visually determined labels, and analyzed 3 existing transcription factor datasets. We observed that default peak detection parameters yield high false positive rates, which can be reduced by learning parameters using a relatively small training set of labeled data from the same experiment type. We also observed that labels from different people are highly consistent. Overall, these data indicate that our supervised labeling method is useful for quantitatively training and testing peak detection algorithms. Availability and Implementation: Labeled histone mark data http://cbio.ensmp.fr/~thocking/chip-seq-chunk-db/, R package to compute the label error of predicted peaks https://github.com/tdhock/PeakError Contacts: toby.hocking@mail.mcgill.ca or guil.bourque@mcgill.ca Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27797775

Optimizing ChIP-seq peak detectors using visual labels and supervised machine learning.

PubMed

Hocking, Toby Dylan; Goerner-Potvin, Patricia; Morin, Andreanne; Shao, Xiaojian; Pastinen, Tomi; Bourque, Guillaume

2017-02-15

Many peak detection algorithms have been proposed for ChIP-seq data analysis, but it is not obvious which algorithm and what parameters are optimal for any given dataset. In contrast, regions with and without obvious peaks can be easily labeled by visual inspection of aligned read counts in a genome browser. We propose a supervised machine learning approach for ChIP-seq data analysis, using labels that encode qualitative judgments about which genomic regions contain or do not contain peaks. The main idea is to manually label a small subset of the genome, and then learn a model that makes consistent peak predictions on the rest of the genome. We created 7 new histone mark datasets with 12 826 visually determined labels, and analyzed 3 existing transcription factor datasets. We observed that default peak detection parameters yield high false positive rates, which can be reduced by learning parameters using a relatively small training set of labeled data from the same experiment type. We also observed that labels from different people are highly consistent. Overall, these data indicate that our supervised labeling method is useful for quantitatively training and testing peak detection algorithms. Labeled histone mark data http://cbio.ensmp.fr/~thocking/chip-seq-chunk-db/ , R package to compute the label error of predicted peaks https://github.com/tdhock/PeakError. toby.hocking@mail.mcgill.ca or guil.bourque@mcgill.ca. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

A non-parametric peak calling algorithm for DamID-Seq.

PubMed

Li, Renhua; Hempel, Leonie U; Jiang, Tingbo

2015-01-01

Protein-DNA interactions play a significant role in gene regulation and expression. In order to identify transcription factor binding sites (TFBS) of double sex (DSX)-an important transcription factor in sex determination, we applied the DNA adenine methylation identification (DamID) technology to the fat body tissue of Drosophila, followed by deep sequencing (DamID-Seq). One feature of DamID-Seq data is that induced adenine methylation signals are not assured to be symmetrically distributed at TFBS, which renders the existing peak calling algorithms for ChIP-Seq, including SPP and MACS, inappropriate for DamID-Seq data. This challenged us to develop a new algorithm for peak calling. A challenge in peaking calling based on sequence data is estimating the averaged behavior of background signals. We applied a bootstrap resampling method to short sequence reads in the control (Dam only). After data quality check and mapping reads to a reference genome, the peaking calling procedure compromises the following steps: 1) reads resampling; 2) reads scaling (normalization) and computing signal-to-noise fold changes; 3) filtering; 4) Calling peaks based on a statistically significant threshold. This is a non-parametric method for peak calling (NPPC). We also used irreproducible discovery rate (IDR) analysis, as well as ChIP-Seq data to compare the peaks called by the NPPC. We identified approximately 6,000 peaks for DSX, which point to 1,225 genes related to the fat body tissue difference between female and male Drosophila. Statistical evidence from IDR analysis indicated that these peaks are reproducible across biological replicates. In addition, these peaks are comparable to those identified by use of ChIP-Seq on S2 cells, in terms of peak number, location, and peaks width.

A ChIP-Seq Data Analysis Pipeline Based on Bioconductor Packages.

PubMed

Park, Seung-Jin; Kim, Jong-Hwan; Yoon, Byung-Ha; Kim, Seon-Young

2017-03-01

Nowadays, huge volumes of chromatin immunoprecipitation-sequencing (ChIP-Seq) data are generated to increase the knowledge on DNA-protein interactions in the cell, and accordingly, many tools have been developed for ChIP-Seq analysis. Here, we provide an example of a streamlined workflow for ChIP-Seq data analysis composed of only four packages in Bioconductor: dada2, QuasR, mosaics, and ChIPseeker. 'dada2' performs trimming of the high-throughput sequencing data. 'QuasR' and 'mosaics' perform quality control and mapping of the input reads to the reference genome and peak calling, respectively. Finally, 'ChIPseeker' performs annotation and visualization of the called peaks. This workflow runs well independently of operating systems (e.g., Windows, Mac, or Linux) and processes the input fastq files into various results in one run. R code is available at github: https://github.com/ddhb/Workflow_of_Chipseq.git.

A ChIP-Seq Data Analysis Pipeline Based on Bioconductor Packages

PubMed Central

Park, Seung-Jin; Kim, Jong-Hwan; Yoon, Byung-Ha; Kim, Seon-Young

2017-01-01

Nowadays, huge volumes of chromatin immunoprecipitation-sequencing (ChIP-Seq) data are generated to increase the knowledge on DNA-protein interactions in the cell, and accordingly, many tools have been developed for ChIP-Seq analysis. Here, we provide an example of a streamlined workflow for ChIP-Seq data analysis composed of only four packages in Bioconductor: dada2, QuasR, mosaics, and ChIPseeker. ‘dada2’ performs trimming of the high-throughput sequencing data. ‘QuasR’ and ‘mosaics’ perform quality control and mapping of the input reads to the reference genome and peak calling, respectively. Finally, ‘ChIPseeker’ performs annotation and visualization of the called peaks. This workflow runs well independently of operating systems (e.g., Windows, Mac, or Linux) and processes the input fastq files into various results in one run. R code is available at github: https://github.com/ddhb/Workflow_of_Chipseq.git. PMID:28416945

Systematic evaluation of the impact of ChIP-seq read designs on genome coverage, peak identification, and allele-specific binding detection.

PubMed

Zhang, Qi; Zeng, Xin; Younkin, Sam; Kawli, Trupti; Snyder, Michael P; Keleş, Sündüz

2016-02-24

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) experiments revolutionized genome-wide profiling of transcription factors and histone modifications. Although maturing sequencing technologies allow these experiments to be carried out with short (36-50 bps), long (75-100 bps), single-end, or paired-end reads, the impact of these read parameters on the downstream data analysis are not well understood. In this paper, we evaluate the effects of different read parameters on genome sequence alignment, coverage of different classes of genomic features, peak identification, and allele-specific binding detection. We generated 101 bps paired-end ChIP-seq data for many transcription factors from human GM12878 and MCF7 cell lines. Systematic evaluations using in silico variations of these data as well as fully simulated data, revealed complex interplay between the sequencing parameters and analysis tools, and indicated clear advantages of paired-end designs in several aspects such as alignment accuracy, peak resolution, and most notably, allele-specific binding detection. Our work elucidates the effect of design on the downstream analysis and provides insights to investigators in deciding sequencing parameters in ChIP-seq experiments. We present the first systematic evaluation of the impact of ChIP-seq designs on allele-specific binding detection and highlights the power of pair-end designs in such studies.

Evaluation of wind-induced internal pressure in low-rise buildings: A multi scale experimental and numerical approach

NASA Astrophysics Data System (ADS)

Tecle, Amanuel Sebhatu

Hurricane is one of the most destructive and costly natural hazard to the built environment and its impact on low-rise buildings, particularity, is beyond acceptable. The major objective of this research was to perform a parametric evaluation of internal pressure (IP) for wind-resistant design of low-rise buildings and wind-driven natural ventilation applications. For this purpose, a multi-scale experimental, i.e. full-scale at Wall of Wind (WoW) and small-scale at Boundary Layer Wind Tunnel (BLWT), and a Computational Fluid Dynamics (CFD) approach was adopted. This provided new capability to assess wind pressures realistically on internal volumes ranging from small spaces formed between roof tiles and its deck to attic to room partitions. Effects of sudden breaching, existing dominant openings on building envelopes as well as compartmentalization of building interior on the IP were systematically investigated. Results of this research indicated: (i) for sudden breaching of dominant openings, the transient overshooting response was lower than the subsequent steady state peak IP and internal volume correction for low-wind-speed testing facilities was necessary. For example a building without volume correction experienced a response four times faster and exhibited 30--40% lower mean and peak IP; (ii) for existing openings, vent openings uniformly distributed along the roof alleviated, whereas one sided openings aggravated the IP; (iii) larger dominant openings exhibited a higher IP on the building envelope, and an off-center opening on the wall exhibited (30--40%) higher IP than center located openings; (iv) compartmentalization amplified the intensity of IP and; (v) significant underneath pressure was measured for field tiles, warranting its consideration during net pressure evaluations. The study aimed at wind driven natural ventilation indicated: (i) the IP due to cross ventilation was 1.5 to 2.5 times higher for Ainlet/Aoutlet>1 compared to cases where Ainlet/Aoutlet<1, this in effect reduced the mixing of air inside the building and hence the ventilation effectiveness; (ii) the presence of multi-room partitioning increased the pressure differential and consequently the air exchange rate. Overall good agreement was found between the observed large-scale, small-scale and CFD based IP responses. Comparisons with ASCE 7-10 consistently demonstrated that the code underestimated peak positive and suction IP.

Separation of a chemically modified DNA oligomer bound by the carcinogen 2-Amino-1-methy-6-phenylimidazo [4,5-{beta}]pyridine using capillary gel electrophoresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, T.N.

1994-05-06

We have optimized the reaction conditions under which unactivated metabolite of the food borne carcinogen 2-amino-1-methyl-6-phenylimidazo [4,5-{beta}]pyridine (PhIP) is covalently bound to the oligodeoxynucleotide d(CCTACGCATCC). Capillary electrophoresis (CE) was used to separate and characterize this DNA oligomer bound by PhIP. We observed 2 major and several minor PhIP adduct species. The 2 major adducts had different absorbance maxima; the major adduct eluates with faster and slower mobilities had absorbance maxima of 360 and 340 nm, respectively. One of the two major PhIP adduct species was resolvable but the peak was broad. Using detection at 260 nm, the other major PhIPmore » adduct with fastest electrophoretic mobility was not resolvable, but coelute with the huge broad unmodified DNA oligomer peak. However, at higher wavelengths (>320 nm) where DNA does not absorb, electropherograms generated by detection at these higher wavelengths showed very heterogeneous binding by PhIP to the DNA oligomer with no interfering absorbance by the DNA.« less

A mathematical model of calcium dynamics in HSY cells

PubMed Central

Han, Jung Min; Tanimura, Akihiko; Kirk, Vivien; Sneyd, James

2017-01-01

Saliva is an essential part of activities such as speaking, masticating and swallowing. Enzymes in salivary fluid protect teeth and gums from infectious diseases, and also initiate the digestion process. Intracellular calcium (Ca2+) plays a critical role in saliva secretion and regulation. Experimental measurements of Ca2+ and inositol trisphosphate (IP3) concentrations in HSY cells, a human salivary duct cell line, show that when the cells are stimulated with adenosine triphosphate (ATP) or carbachol (CCh), they exhibit coupled oscillations with Ca2+ spike peaks preceding IP3 spike peaks. Based on these data, we construct a mathematical model of coupled Ca2+ and IP3 oscillations in HSY cells and perform model simulations of three different experimental settings to forecast Ca2+ responses. The model predicts that when Ca2+ influx from the extracellular space is removed, oscillations gradually slow down until they stop. The model simulation of applying a pulse of IP3 predicts that photolysis of caged IP3 causes a transient increase in the frequency of the Ca2+ oscillations. Lastly, when Ca2+-dependent activation of PLC is inhibited, we see an increase in the oscillation frequency and a decrease in the amplitude. These model predictions are confirmed by experimental data. We conclude that, although concentrations of Ca2+ and IP3 oscillate, Ca2+ oscillations in HSY cells are the result of modulation of the IP3 receptor by intracellular Ca2+, and that the period is modulated by the accompanying IP3 oscillations. PMID:28199326

DROMPA: easy-to-handle peak calling and visualization software for the computational analysis and validation of ChIP-seq data.

PubMed

Nakato, Ryuichiro; Itoh, Tahehiko; Shirahige, Katsuhiko

2013-07-01

Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) can identify genomic regions that bind proteins involved in various chromosomal functions. Although the development of next-generation sequencers offers the technology needed to identify these protein-binding sites, the analysis can be computationally challenging because sequencing data sometimes consist of >100 million reads/sample. Herein, we describe a cost-effective and time-efficient protocol that is generally applicable to ChIP-seq analysis; this protocol uses a novel peak-calling program termed DROMPA to identify peaks and an additional program, parse2wig, to preprocess read-map files. This two-step procedure drastically reduces computational time and memory requirements compared with other programs. DROMPA enables the identification of protein localization sites in repetitive sequences and efficiently identifies both broad and sharp protein localization peaks. Specifically, DROMPA outputs a protein-binding profile map in pdf or png format, which can be easily manipulated by users who have a limited background in bioinformatics. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Broad-Enrich: functional interpretation of large sets of broad genomic regions.

PubMed

Cavalcante, Raymond G; Lee, Chee; Welch, Ryan P; Patil, Snehal; Weymouth, Terry; Scott, Laura J; Sartor, Maureen A

2014-09-01

Functional enrichment testing facilitates the interpretation of Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data in terms of pathways and other biological contexts. Previous methods developed and used to test for key gene sets affected in ChIP-seq experiments treat peaks as points, and are based on the number of peaks associated with a gene or a binary score for each gene. These approaches work well for transcription factors, but histone modifications often occur over broad domains, and across multiple genes. To incorporate the unique properties of broad domains into functional enrichment testing, we developed Broad-Enrich, a method that uses the proportion of each gene's locus covered by a peak. We show that our method has a well-calibrated false-positive rate, performing well with ChIP-seq data having broad domains compared with alternative approaches. We illustrate Broad-Enrich with 55 ENCODE ChIP-seq datasets using different methods to define gene loci. Broad-Enrich can also be applied to other datasets consisting of broad genomic domains such as copy number variations. http://broad-enrich.med.umich.edu for Web version and R package. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

Electrophysiological correlates of stimulus-driven reorienting deficits after interference with right parietal cortex during a spatial attention task: a TMS-EEG study

PubMed Central

Capotosto, Paolo; Corbetta, Maurizio; Romani, Gian Luca; Babiloni, Claudio

2013-01-01

Transcranial magnetic stimulation (TMS) interference over right intraparietal sulcus (IPS) causally disrupts behaviorally and electroencephalographic (EEG) rhythmic correlates of endogenous spatial orienting prior to visual target presentation (Capotosto et al. 2009; 2011). Here we combine data from our previous studies to examine whether right parietal TMS during spatial orienting also impairs stimulus-driven re-orienting or the ability to efficiently process unattended stimuli, i.e. stimuli outside the current focus of attention. Healthy subjects (N=24) performed a Posner spatial cueing task while their EEG activity was being monitored. Repetitive TMS (rTMS) was applied for 150 milliseconds (ms) simultaneously to the presentation of a central arrow directing spatial attention to the location of an upcoming visual target. Right IPS-rTMS impaired target detection, especially for stimuli presented at unattended locations; it also caused a modulation of the amplitude of parieto-occipital positive ERPs peaking at about 480 ms (P3) post-target. The P3 significantly decreased for unattended targets, and significantly increased for attended targets after right IPS-rTMS as compared to Sham stimulation. Similar effects were obtained for left IPS stimulation albeit in a smaller group of subjects. We conclude that disruption of anticipatory processes in right IPS has prolonged effects that persist during target processing. The P3 decrement may reflect interference with post-decision processes that are part of stimulus-driven re-orienting. Right IPS is a node of functional interaction between endogenous spatial orienting and stimulus-driven re-orienting processes in human vision. PMID:22905824

Q-nexus: a comprehensive and efficient analysis pipeline designed for ChIP-nexus.

PubMed

Hansen, Peter; Hecht, Jochen; Ibn-Salem, Jonas; Menkuec, Benjamin S; Roskosch, Sebastian; Truss, Matthias; Robinson, Peter N

2016-11-04

ChIP-nexus, an extension of the ChIP-exo protocol, can be used to map the borders of protein-bound DNA sequences at nucleotide resolution, requires less input DNA and enables selective PCR duplicate removal using random barcodes. However, the use of random barcodes requires additional preprocessing of the mapping data, which complicates the computational analysis. To date, only a very limited number of software packages are available for the analysis of ChIP-exo data, which have not yet been systematically tested and compared on ChIP-nexus data. Here, we present a comprehensive software package for ChIP-nexus data that exploits the random barcodes for selective removal of PCR duplicates and for quality control. Furthermore, we developed bespoke methods to estimate the width of the protected region resulting from protein-DNA binding and to infer binding positions from ChIP-nexus data. Finally, we applied our peak calling method as well as the two other methods MACE and MACS2 to the available ChIP-nexus data. The Q-nexus software is efficient and easy to use. Novel statistics about duplication rates in consideration of random barcodes are calculated. Our method for the estimation of the width of the protected region yields unbiased signatures that are highly reproducible for biological replicates and at the same time very specific for the respective factors analyzed. As judged by the irreproducible discovery rate (IDR), our peak calling algorithm shows a substantially better reproducibility. An implementation of Q-nexus is available at http://charite.github.io/Q/ .

Picking ChIP-seq peak detectors for analyzing chromatin modification experiments

PubMed Central

Micsinai, Mariann; Parisi, Fabio; Strino, Francesco; Asp, Patrik; Dynlacht, Brian D.; Kluger, Yuval

2012-01-01

Numerous algorithms have been developed to analyze ChIP-Seq data. However, the complexity of analyzing diverse patterns of ChIP-Seq signals, especially for epigenetic marks, still calls for the development of new algorithms and objective comparisons of existing methods. We developed Qeseq, an algorithm to detect regions of increased ChIP read density relative to background. Qeseq employs critical novel elements, such as iterative recalibration and neighbor joining of reads to identify enriched regions of any length. To objectively assess its performance relative to other 14 ChIP-Seq peak finders, we designed a novel protocol based on Validation Discriminant Analysis (VDA) to optimally select validation sites and generated two validation datasets, which are the most comprehensive to date for algorithmic benchmarking of key epigenetic marks. In addition, we systematically explored a total of 315 diverse parameter configurations from these algorithms and found that typically optimal parameters in one dataset do not generalize to other datasets. Nevertheless, default parameters show the most stable performance, suggesting that they should be used. This study also provides a reproducible and generalizable methodology for unbiased comparative analysis of high-throughput sequencing tools that can facilitate future algorithmic development. PMID:22307239

Picking ChIP-seq peak detectors for analyzing chromatin modification experiments.

PubMed

Micsinai, Mariann; Parisi, Fabio; Strino, Francesco; Asp, Patrik; Dynlacht, Brian D; Kluger, Yuval

2012-05-01

Numerous algorithms have been developed to analyze ChIP-Seq data. However, the complexity of analyzing diverse patterns of ChIP-Seq signals, especially for epigenetic marks, still calls for the development of new algorithms and objective comparisons of existing methods. We developed Qeseq, an algorithm to detect regions of increased ChIP read density relative to background. Qeseq employs critical novel elements, such as iterative recalibration and neighbor joining of reads to identify enriched regions of any length. To objectively assess its performance relative to other 14 ChIP-Seq peak finders, we designed a novel protocol based on Validation Discriminant Analysis (VDA) to optimally select validation sites and generated two validation datasets, which are the most comprehensive to date for algorithmic benchmarking of key epigenetic marks. In addition, we systematically explored a total of 315 diverse parameter configurations from these algorithms and found that typically optimal parameters in one dataset do not generalize to other datasets. Nevertheless, default parameters show the most stable performance, suggesting that they should be used. This study also provides a reproducible and generalizable methodology for unbiased comparative analysis of high-throughput sequencing tools that can facilitate future algorithmic development.

ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data

PubMed Central

2010-01-01

Background Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) or ChIP followed by genome tiling array analysis (ChIP-chip) have become standard technologies for genome-wide identification of DNA-binding protein target sites. A number of algorithms have been developed in parallel that allow identification of binding sites from ChIP-seq or ChIP-chip datasets and subsequent visualization in the University of California Santa Cruz (UCSC) Genome Browser as custom annotation tracks. However, summarizing these tracks can be a daunting task, particularly if there are a large number of binding sites or the binding sites are distributed widely across the genome. Results We have developed ChIPpeakAnno as a Bioconductor package within the statistical programming environment R to facilitate batch annotation of enriched peaks identified from ChIP-seq, ChIP-chip, cap analysis of gene expression (CAGE) or any experiments resulting in a large number of enriched genomic regions. The binding sites annotated with ChIPpeakAnno can be viewed easily as a table, a pie chart or plotted in histogram form, i.e., the distribution of distances to the nearest genes for each set of peaks. In addition, we have implemented functionalities for determining the significance of overlap between replicates or binding sites among transcription factors within a complex, and for drawing Venn diagrams to visualize the extent of the overlap between replicates. Furthermore, the package includes functionalities to retrieve sequences flanking putative binding sites for PCR amplification, cloning, or motif discovery, and to identify Gene Ontology (GO) terms associated with adjacent genes. Conclusions ChIPpeakAnno enables batch annotation of the binding sites identified from ChIP-seq, ChIP-chip, CAGE or any technology that results in a large number of enriched genomic regions within the statistical programming environment R. Allowing users to pass their own annotation data such as a different Chromatin immunoprecipitation (ChIP) preparation and a dataset from literature, or existing annotation packages, such as GenomicFeatures and BSgenome, provides flexibility. Tight integration to the biomaRt package enables up-to-date annotation retrieval from the BioMart database. PMID:20459804

Optimization of process parameters of pulsed TIG welded maraging steel C300

NASA Astrophysics Data System (ADS)

Deepak, P.; Jualeash, M. J.; Jishnu, J.; Srinivasan, P.; Arivarasu, M.; Padmanaban, R.; Thirumalini, S.

2016-09-01

Pulsed TIG welding technology provides excellent welding performance on thin sections which helps to increase productivity, enhance weld quality, minimize weld costs, and boost operator efficiency and this has drawn the attention of the welding society. Maraging C300 steel is extensively used in defence and aerospace industry and thus its welding becomes an area of paramount importance. In pulsed TIG welding, weld quality depends on the process parameters used. In this work, Pulsed TIG bead-on-plate welding is performed on a 5mm thick maraging C300 plate at different combinations of input parameters: peak current (Ip), base current (Ib) and pulsing frequency (HZ) as per box behnken design with three-levels for each factor. Response surface methodology is utilized for establishing a mathematical model for predicting the weld bead depth. The effect of Ip, Ib and HZ on the weld bead depth is investigated using the developed model. The weld bead depth is found to be affected by all the three parameters. Surface and contour plots developed from regression equation are used to optimize the processing parameters for maximizing the weld bead depth. Optimum values of Ip, Ib and HZ are obtained as 259 A, 120 A and 8 Hz respectively. Using this optimum condition, maximum bead depth of the weld is predicted to be 4.325 mm.

iTAR: a web server for identifying target genes of transcription factors using ChIP-seq or ChIP-chip data.

PubMed

Yang, Chia-Chun; Andrews, Erik H; Chen, Min-Hsuan; Wang, Wan-Yu; Chen, Jeremy J W; Gerstein, Mark; Liu, Chun-Chi; Cheng, Chao

2016-08-12

Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) or microarray hybridization (ChIP-chip) has been widely used to determine the genomic occupation of transcription factors (TFs). We have previously developed a probabilistic method, called TIP (Target Identification from Profiles), to identify TF target genes using ChIP-seq/ChIP-chip data. To achieve high specificity, TIP applies a conservative method to estimate significance of target genes, with the trade-off being a relatively low sensitivity of target gene identification compared to other methods. Additionally, TIP's output does not render binding-peak locations or intensity, information highly useful for visualization and general experimental biological use, while the variability of ChIP-seq/ChIP-chip file formats has made input into TIP more difficult than desired. To improve upon these facets, here we present are fined TIP with key extensions. First, it implements a Gaussian mixture model for p-value estimation, increasing target gene identification sensitivity and more accurately capturing the shape of TF binding profile distributions. Second, it enables the incorporation of TF binding-peak data by identifying their locations in significant target gene promoter regions and quantifies their strengths. Finally, for full ease of implementation we have incorporated it into a web server ( http://syslab3.nchu.edu.tw/iTAR/ ) that enables flexibility of input file format, can be used across multiple species and genome assembly versions, and is freely available for public use. The web server additionally performs GO enrichment analysis for the identified target genes to reveal the potential function of the corresponding TF. The iTAR web server provides a user-friendly interface and supports target gene identification in seven species, ranging from yeast to human. To facilitate investigating the quality of ChIP-seq/ChIP-chip data, the web server generates the chart of the characteristic binding profiles and the density plot of normalized regulatory scores. The iTAR web server is a useful tool in identifying TF target genes from ChIP-seq/ChIP-chip data and discovering biological insights.

KChIP1 modulation of Kv4.3-mediated A-type K(+) currents and repetitive firing in hippocampal interneurons.

PubMed

Bourdeau, M L; Laplante, I; Laurent, C E; Lacaille, J-C

2011-03-10

Neuronal A-type K(+) channels regulate action potential waveform, back-propagation and firing frequency. In hippocampal CA1 interneurons located at the stratum lacunosum-moleculare/radiatum junction (LM/RAD), Kv4.3 mediates A-type K(+) currents and a Kv4 β-subunit of the Kv channel interacting protein (KChIP) family, KChIP1, appears specifically expressed in these cells. However, the functional role of this accessory subunit in A-type K(+) currents and interneuron excitability remains largely unknown. Thus, first we studied KChIP1 and Kv4.3 channel interactions in human embryonic kidney 293 (HEK293) cells and determined that KChIP1 coexpression modulated the biophysical properties of Kv4.3 A-type currents (faster recovery from inactivation, leftward shift of activation curve, faster rise time and slower decay) and this modulation was selectively prevented by KChIP1 short interfering RNA (siRNA) knockdown. Next, we evaluated the effects of KChIP1 down-regulation by siRNA on A-type K(+) currents in LM/RAD interneurons in slice cultures. Recovery from inactivation of A-type K(+) currents was slower after KChIP1 down-regulation but other properties were unchanged. In addition, down-regulation of KChIP1 levels did not affect action potential waveform and firing, but increased firing frequency during suprathreshold depolarizations, indicating that KChIP1 regulates interneuron excitability. The effects of KChIP1 down-regulation were cell-specific since CA1 pyramidal cells that do not express KChIP1 were unaffected. Overall, our findings suggest that KChIP1 interacts with Kv4.3 in LM/RAD interneurons, enabling faster recovery from inactivation of A-type currents and thus promoting stronger inhibitory control of firing during sustained activity. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

A MAD-Bayes Algorithm for State-Space Inference and Clustering with Application to Querying Large Collections of ChIP-Seq Data Sets.

PubMed

Zuo, Chandler; Chen, Kailei; Keleş, Sündüz

2017-06-01

Current analytic approaches for querying large collections of chromatin immunoprecipitation followed by sequencing (ChIP-seq) data from multiple cell types rely on individual analysis of each data set (i.e., peak calling) independently. This approach discards the fact that functional elements are frequently shared among related cell types and leads to overestimation of the extent of divergence between different ChIP-seq samples. Methods geared toward multisample investigations have limited applicability in settings that aim to integrate 100s to 1000s of ChIP-seq data sets for query loci (e.g., thousands of genomic loci with a specific binding site). Recently, Zuo et al. developed a hierarchical framework for state-space matrix inference and clustering, named MBASIC, to enable joint analysis of user-specified loci across multiple ChIP-seq data sets. Although this versatile framework estimates both the underlying state-space (e.g., bound vs. unbound) and also groups loci with similar patterns together, its Expectation-Maximization-based estimation structure hinders its applicability with large number of loci and samples. We address this limitation by developing MAP-based asymptotic derivations from Bayes (MAD-Bayes) framework for MBASIC. This results in a K-means-like optimization algorithm that converges rapidly and hence enables exploring multiple initialization schemes and flexibility in tuning. Comparison with MBASIC indicates that this speed comes at a relatively insignificant loss in estimation accuracy. Although MAD-Bayes MBASIC is specifically designed for the analysis of user-specified loci, it is able to capture overall patterns of histone marks from multiple ChIP-seq data sets similar to those identified by genome-wide segmentation methods such as ChromHMM and Spectacle.

Network analysis of ChIP-Seq data reveals key genes in prostate cancer.

PubMed

Zhang, Yu; Huang, Zhen; Zhu, Zhiqiang; Liu, Jianwei; Zheng, Xin; Zhang, Yuhai

2014-09-03

Prostate cancer (PC) is the second most common cancer among men in the United States, and it imposes a considerable threat to human health. A deep understanding of its underlying molecular mechanisms is the premise for developing effective targeted therapies. Recently, deep transcriptional sequencing has been used as an effective genomic assay to obtain insights into diseases and may be helpful in the study of PC. In present study, ChIP-Seq data for PC and normal samples were compared, and differential peaks identified, based upon fold changes (with P-values calculated with t-tests). Annotations of these peaks were performed. Protein-protein interaction (PPI) network analysis was performed with BioGRID and constructed with Cytoscape, following which the highly connected genes were screened. We obtained a total of 5,570 differential peaks, including 3,726 differentially enriched peaks in tumor samples and 1,844 differentially enriched peaks in normal samples. There were eight significant regions of the peaks. The intergenic region possessed the highest score (51%), followed by intronic (31%) and exonic (11%) regions. The analysis revealed the top 35 highly connected genes, which comprised 33 differential genes (such as YWHAQ, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein and θ polypeptide) from ChIP-Seq data and 2 differential genes retrieved from the PPI network: UBA52 (ubiquitin A-52 residue ribosomal protein fusion product (1) and SUMO2 (SMT3 suppressor of mif two 3 homolog (2) . Our findings regarding potential PC-related genes increase the understanding of PC and provides direction for future research.

Small negative cloud-to-ground lightning reports at the NASA Kennedy Space Center and Air Force Eastern Range

NASA Astrophysics Data System (ADS)

Wilson, Jennifer G.; Cummins, Kenneth L.; Krider, E. Philip

2009-12-01

The NASA Kennedy Space Center (KSC) and Air Force Eastern Range (ER) use data from two cloud-to-ground (CG) lightning detection networks, the Cloud-to-Ground Lightning Surveillance System (CGLSS) and the U.S. National Lightning Detection Network™ (NLDN), and a volumetric lightning mapping array, the Lightning Detection and Ranging (LDAR) system, to monitor and characterize lightning that is potentially hazardous to launch or ground operations. Data obtained from these systems during June-August 2006 have been examined to check the classification of small, negative CGLSS reports that have an estimated peak current, ∣Ip∣ less than 7 kA, and to determine the smallest values of Ip that are produced by first strokes, by subsequent strokes that create a new ground contact (NGC), and by subsequent strokes that remain in a preexisting channel (PEC). The results show that within 20 km of the KSC-ER, 21% of the low-amplitude negative CGLSS reports were produced by first strokes, with a minimum Ip of -2.9 kA; 31% were by NGCs, with a minimum Ip of -2.0 kA; and 14% were by PECs, with a minimum Ip of -2.2 kA. The remaining 34% were produced by cloud pulses or lightning events that we were not able to classify.

A novel statistical method for quantitative comparison of multiple ChIP-seq datasets.

PubMed

Chen, Li; Wang, Chi; Qin, Zhaohui S; Wu, Hao

2015-06-15

ChIP-seq is a powerful technology to measure the protein binding or histone modification strength in the whole genome scale. Although there are a number of methods available for single ChIP-seq data analysis (e.g. 'peak detection'), rigorous statistical method for quantitative comparison of multiple ChIP-seq datasets with the considerations of data from control experiment, signal to noise ratios, biological variations and multiple-factor experimental designs is under-developed. In this work, we develop a statistical method to perform quantitative comparison of multiple ChIP-seq datasets and detect genomic regions showing differential protein binding or histone modification. We first detect peaks from all datasets and then union them to form a single set of candidate regions. The read counts from IP experiment at the candidate regions are assumed to follow Poisson distribution. The underlying Poisson rates are modeled as an experiment-specific function of artifacts and biological signals. We then obtain the estimated biological signals and compare them through the hypothesis testing procedure in a linear model framework. Simulations and real data analyses demonstrate that the proposed method provides more accurate and robust results compared with existing ones. An R software package ChIPComp is freely available at http://web1.sph.emory.edu/users/hwu30/software/ChIPComp.html. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain.

PubMed

Holmqvist, Mats H; Cao, Jie; Hernandez-Pineda, Ricardo; Jacobson, Michael D; Carroll, Karen I; Sung, M Amy; Betty, Maria; Ge, Pei; Gilbride, Kevin J; Brown, Melissa E; Jurman, Mark E; Lawson, Deborah; Silos-Santiago, Inmaculada; Xie, Yu; Covarrubias, Manuel; Rhodes, Kenneth J; Distefano, Peter S; An, W Frank

2002-01-22

The Kv4 A-type potassium currents contribute to controlling the frequency of slow repetitive firing and back-propagation of action potentials in neurons and shape the action potential in heart. Kv4 currents exhibit rapid activation and inactivation and are specifically modulated by K-channel interacting proteins (KChIPs). Here we report the discovery and functional characterization of a modular K-channel inactivation suppressor (KIS) domain located in the first 34 aa of an additional KChIP (KChIP4a). Coexpression of KChIP4a with Kv4 alpha-subunits abolishes fast inactivation of the Kv4 currents in various cell types, including cerebellar granule neurons. Kinetic analysis shows that the KIS domain delays Kv4.3 opening, but once the channel is open, it disrupts rapid inactivation and slows Kv4.3 closing. Accordingly, KChIP4a increases the open probability of single Kv4.3 channels. The net effects of KChIP4a and KChIP1-3 on Kv4 gating are quite different. When both KChIP4a and KChIP1 are present, the Kv4.3 current shows mixed inactivation profiles dependent on KChIP4a/KChIP1 ratios. The KIS domain effectively converts the A-type Kv4 current to a slowly inactivating delayed rectifier-type potassium current. This conversion is opposite to that mediated by the Kv1-specific "ball" domain of the Kv beta 1 subunit. Together, these results demonstrate that specific auxiliary subunits with distinct functions actively modulate gating of potassium channels that govern membrane excitability.

Massive stars dying alone: the extremely remote environment of SN 2009ip

NASA Astrophysics Data System (ADS)

Smith, Nathan; Andrews, Jennifer E.; Mauerhan, Jon C.

2016-12-01

We present late-time Hubble Space Telescope (HST) images of the site of supernova (SN) 2009ip taken almost 3 yr after its bright 2012 luminosity peak. SN 2009ip is now slightly fainter in broad filters than the progenitor candidate detected by HST in 1999. The current source continues to be dominated by ongoing late-time circumstellar material interaction that produces strong Hα emission and a weak pseudo-continuum, as found previously for 1-2 yr after explosion. The intent of these observations was to search for evidence of recent star formation in the local (˜1 kpc; 10 arcsec) environment around SN 2009ip, in the remote outskirts of its host spiral galaxy NGC 7259. We can rule out the presence of any massive star-forming complexes like 30 Dor or the Carina nebula at the SN site or within a few kpc. If the progenitor of SN 2009ip was really a 50-80 M⊙ star as archival HST images suggested, then it is strange that there is no sign of this type of massive star formation anywhere in the vicinity. A possible explanation is that the progenitor was the product of a merger or binary mass transfer, rejuvenated after a lifetime that was much longer than 4-5 Myr, allowing its natal H II region to have faded. A smaller region like the Orion nebula would be an unresolved but easily detected point source. This is ruled out within ˜1.5 kpc around SN 2009ip, but a small H II region could be hiding in the glare of SN 2009ip itself. Later images after a few more years have passed are needed to confirm that the progenitor candidate is truly gone and to test for the possibility of a small H II region or cluster at the SN position.

The Role of Genome Accessibility in Transcription Factor Binding in Bacteria.

PubMed

Gomes, Antonio L C; Wang, Harris H

2016-04-01

ChIP-seq enables genome-scale identification of regulatory regions that govern gene expression. However, the biological insights generated from ChIP-seq analysis have been limited to predictions of binding sites and cooperative interactions. Furthermore, ChIP-seq data often poorly correlate with in vitro measurements or predicted motifs, highlighting that binding affinity alone is insufficient to explain transcription factor (TF)-binding in vivo. One possibility is that binding sites are not equally accessible across the genome. A more comprehensive biophysical representation of TF-binding is required to improve our ability to understand, predict, and alter gene expression. Here, we show that genome accessibility is a key parameter that impacts TF-binding in bacteria. We developed a thermodynamic model that parameterizes ChIP-seq coverage in terms of genome accessibility and binding affinity. The role of genome accessibility is validated using a large-scale ChIP-seq dataset of the M. tuberculosis regulatory network. We find that accounting for genome accessibility led to a model that explains 63% of the ChIP-seq profile variance, while a model based in motif score alone explains only 35% of the variance. Moreover, our framework enables de novo ChIP-seq peak prediction and is useful for inferring TF-binding peaks in new experimental conditions by reducing the need for additional experiments. We observe that the genome is more accessible in intergenic regions, and that increased accessibility is positively correlated with gene expression and anti-correlated with distance to the origin of replication. Our biophysically motivated model provides a more comprehensive description of TF-binding in vivo from first principles towards a better representation of gene regulation in silico, with promising applications in systems biology.

Stably Fluorescent Cell Line of Human Ovarian Epithelial Cancer Cells SK-OV-3ip-red.

PubMed

Konovalova, E V; Shulga, A A; Chumakov, S P; Khodarovich, Yu M; Woo, Eui-Jeon; Deev, S M

2017-11-01

Stable red fluorescing line of human ovarian epithelial cancer cells SK-OV-3ip-red was generated expressing gene coding for protein TurboFP635 (Katushka) fluorescing in the far-red spectrum region with excitation and emission peaks at 588 and 635 nm, respectively. Fluorescence of SK-OV-3ip-red line remained high during long-term cell culturing and after cryogenic freezing. The obtained cell line SK-OV-3ip-red can serve a basis for a model of a scattered tumor with numerous/extended metastases and used both for testing anticancer drugs inhibiting metastasis growth and for non-invasive monitoring of the growth dynamics with high precision.

Electron Temperature Evolution During Local Helicity Injection on the Pegasus Toroidal Experiment

NASA Astrophysics Data System (ADS)

Schlossberg, D. J.; Barr, J. L.; Bodner, G. M.; Bongard, M. W.; Fonck, R. J.; Perry, J. M.; Reusch, J. A.; Rodriguez Sanchez, C.

2016-10-01

Understanding the electron temperature (Te) evolution during local helicity injection (LHI) is critical for scaling up this non-solenoidal startup technique to MA-class devices. The first comprehensive Te measurements during LHI reveal centrally-peaked profiles with Te > 100 eV for plasma current Ip > 120 kA, toroidal field 0.15 T, and electron density ne 1019 m-3. Te rises and is sustained from just after magnetic relaxation through the plasma decoupling from edge-localized injectors. Results are presented for two injector edge locations: outboard midplane and inboard divertor. Outboard midplane injection couples LHI with inductive drive from poloidal field ramps and radial compression during inward plasma growth. Comparisons of Te at different LHI-to-inductive drive ratios show some profile flattening for higher LHI drive fraction. The latter, constant-shape discharges were necessarily lower performance, with Ip 50 kA and reduced Te , max. Inboard divertor injection achieves higher Ip using minimal inductive drive and thus isolates effects of LHI drive on Te. Initial results in this configuration show Te rising rapidly at the injector location as the discharge grows, settling to a roughly flat profile 100 eV. Thus far, both scenarios provide relatively stable discharges with moderate ne and high-Te, suitable for coupling to auxiliary current drive. Detailed studies of confinement dynamics and discharge optimization are planned for the near future. Work supported by US DOE Grant DE-FG02-96ER54375.

ChIPWig: a random access-enabling lossless and lossy compression method for ChIP-seq data.

PubMed

Ravanmehr, Vida; Kim, Minji; Wang, Zhiying; Milenkovic, Olgica

2018-03-15

Chromatin immunoprecipitation sequencing (ChIP-seq) experiments are inexpensive and time-efficient, and result in massive datasets that introduce significant storage and maintenance challenges. To address the resulting Big Data problems, we propose a lossless and lossy compression framework specifically designed for ChIP-seq Wig data, termed ChIPWig. ChIPWig enables random access, summary statistics lookups and it is based on the asymptotic theory of optimal point density design for nonuniform quantizers. We tested the ChIPWig compressor on 10 ChIP-seq datasets generated by the ENCODE consortium. On average, lossless ChIPWig reduced the file sizes to merely 6% of the original, and offered 6-fold compression rate improvement compared to bigWig. The lossy feature further reduced file sizes 2-fold compared to the lossless mode, with little or no effects on peak calling and motif discovery using specialized NarrowPeaks methods. The compression and decompression speed rates are of the order of 0.2 sec/MB using general purpose computers. The source code and binaries are freely available for download at https://github.com/vidarmehr/ChIPWig-v2, implemented in C ++. milenkov@illinois.edu. Supplementary data are available at Bioinformatics online.

Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and gating.

PubMed

Bähring, R; Dannenberg, J; Peters, H C; Leicher, T; Pongs, O; Isbrandt, D

2001-06-29

Association of Kv channel-interacting proteins (KChIPs) with Kv4 channels leads to modulation of these A-type potassium channels (An, W. F., Bowlby, M. R., Betty, M., Cao, J., Ling, H. P., Mendoza, G., Hinson, J. W., Mattsson, K. I., Strassle, B. W., Trimmer, J. S., and Rhodes, K. J. (2000) Nature 403, 553-556). We cloned a KChIP2 splice variant (KChIP2.2) from human ventricle. In comparison with KChIP2.1, coexpression of KChIP2.2 with human Kv4 channels in mammalian cells slowed the onset of Kv4 current inactivation (2-3-fold), accelerated the recovery from inactivation (5-7-fold), and shifted Kv4 steady-state inactivation curves by 8-29 mV to more positive potentials. The features of Kv4.2/KChIP2.2 currents closely resemble those of cardiac rapidly inactivating transient outward currents. KChIP2.2 stimulated the Kv4 current density in Chinese hamster ovary cells by approximately 55-fold. This correlated with a redistribution of immunoreactivity from perinuclear areas to the plasma membrane. Increased Kv4 cell-surface expression and current density were also obtained in the absence of KChIP2.2 when the highly conserved proximal Kv4 N terminus was deleted. The same domain is required for association of KChIP2.2 with Kv4 alpha-subunits. We propose that an efficient transport of Kv4 channels to the cell surface depends on KChIP binding to the Kv4 N-terminal domain. Our data suggest that the binding is necessary, but not sufficient, for the functional activity of KChIPs.

KChIP2 genotype dependence of transient outward current (Ito) properties in cardiomyocytes isolated from male and female mice

PubMed Central

Waldschmidt, Lara; Junkereit, Vera; Bähring, Robert

2017-01-01

The transient outward current (Ito) in cardiomyocytes is largely mediated by Kv4 channels associated with Kv Channel Interacting Protein 2 (KChIP2). A knockout model has documented the critical role of KChIP2 in Ito expression. The present study was conducted to characterize in both sexes the dependence of Ito properties, including current magnitude, inactivation kinetics, recovery from inactivation and voltage dependence of inactivation, on the number of functional KChIP2 alleles. For this purpose we performed whole-cell patch-clamp experiments on isolated left ventricular cardiomyocytes from male and female mice which had different KChIP2 genotypes; i.e., wild-type (KChIP2+/+), heterozygous knockout (KChIP2+/-) or complete knockout of KChIP2 (KChIP2-/-). We found in both sexes a KChIP2 gene dosage effect (i.e., a proportionality between number of alleles and phenotype) on Ito magnitude, however, concerning other Ito properties, KChIP2+/- resembled KChIP2+/+. Only in the total absence of KChIP2 (KChIP2-/-) we observed a slowing of Ito kinetics, a slowing of recovery from inactivation and a negative shift of a portion of the voltage dependence of inactivation. In a minor fraction of KChIP2-/- myocytes Ito was completely lost. The distinct KChIP2 genotype dependences of Ito magnitude and inactivation kinetics, respectively, seen in cardiomyocytes were reproduced with two-electrode voltage-clamp experiments on Xenopus oocytes expressing Kv4.2 and different amounts of KChIP2. Our results corroborate the critical role of KChIP2 in controlling Ito properties. They demonstrate that the Kv4.2/KChIP2 interaction in cardiomyocytes is highly dynamic, with a clear KChIP2 gene dosage effect on Kv4 channel surface expression but not on inactivation gating. PMID:28141821

KChIP2 genotype dependence of transient outward current (Ito) properties in cardiomyocytes isolated from male and female mice.

PubMed

Waldschmidt, Lara; Junkereit, Vera; Bähring, Robert

2017-01-01

The transient outward current (Ito) in cardiomyocytes is largely mediated by Kv4 channels associated with Kv Channel Interacting Protein 2 (KChIP2). A knockout model has documented the critical role of KChIP2 in Ito expression. The present study was conducted to characterize in both sexes the dependence of Ito properties, including current magnitude, inactivation kinetics, recovery from inactivation and voltage dependence of inactivation, on the number of functional KChIP2 alleles. For this purpose we performed whole-cell patch-clamp experiments on isolated left ventricular cardiomyocytes from male and female mice which had different KChIP2 genotypes; i.e., wild-type (KChIP2+/+), heterozygous knockout (KChIP2+/-) or complete knockout of KChIP2 (KChIP2-/-). We found in both sexes a KChIP2 gene dosage effect (i.e., a proportionality between number of alleles and phenotype) on Ito magnitude, however, concerning other Ito properties, KChIP2+/- resembled KChIP2+/+. Only in the total absence of KChIP2 (KChIP2-/-) we observed a slowing of Ito kinetics, a slowing of recovery from inactivation and a negative shift of a portion of the voltage dependence of inactivation. In a minor fraction of KChIP2-/- myocytes Ito was completely lost. The distinct KChIP2 genotype dependences of Ito magnitude and inactivation kinetics, respectively, seen in cardiomyocytes were reproduced with two-electrode voltage-clamp experiments on Xenopus oocytes expressing Kv4.2 and different amounts of KChIP2. Our results corroborate the critical role of KChIP2 in controlling Ito properties. They demonstrate that the Kv4.2/KChIP2 interaction in cardiomyocytes is highly dynamic, with a clear KChIP2 gene dosage effect on Kv4 channel surface expression but not on inactivation gating.

Studies on impact of electron cyclotron wave injection on the internal transport barriers in JT-60U weak shear plasmas

NASA Astrophysics Data System (ADS)

Ide, S.; Takenaga, H.; Isayama, A.; Sakamoto, Y.; Yoshida, M.; Gormezano, C.

2007-11-01

Impact of the electron cyclotron range of frequency wave (ECRF) on the internal transport barriers (ITBs) in a weak shear (WS) plasma has been investigated in JT-60U. The fundamental O-mode ECRF of 110 GHz injected obliquely (co-current drive) from the low field side is used. It is observed that the ion temperature (Ti) ITB in a WS plasma can be degraded by ECRF. It is clarified for the first time that the degradation depends increasingly on the EC power (PEC) but decreasingly on the plasma current (Ip). Moreover it is confirmed that ECRF affects the toroidal rotation (Vt) indirectly and results in the flattening of Vt(ρ) and therefore the radial electric field (Er) profiles regardless of the direction of the target Vt(ρ), peaking co or counter direction (relative to the Ip direction). Furthermore, it is recently found that Ti and Vt in the whole ITB region are affected with almost no delay from the EC onset even with off-axis EC deposition. These results indicate that EC injection unveiled a semi-global structure that characterizes Ti ITB in a WS plasma.

Is this the right normalization? A diagnostic tool for ChIP-seq normalization.

PubMed

Angelini, Claudia; Heller, Ruth; Volkinshtein, Rita; Yekutieli, Daniel

2015-05-09

Chip-seq experiments are becoming a standard approach for genome-wide profiling protein-DNA interactions, such as detecting transcription factor binding sites, histone modification marks and RNA Polymerase II occupancy. However, when comparing a ChIP sample versus a control sample, such as Input DNA, normalization procedures have to be applied in order to remove experimental source of biases. Despite the substantial impact that the choice of the normalization method can have on the results of a ChIP-seq data analysis, their assessment is not fully explored in the literature. In particular, there are no diagnostic tools that show whether the applied normalization is indeed appropriate for the data being analyzed. In this work we propose a novel diagnostic tool to examine the appropriateness of the estimated normalization procedure. By plotting the empirical densities of log relative risks in bins of equal read count, along with the estimated normalization constant, after logarithmic transformation, the researcher is able to assess the appropriateness of the estimated normalization constant. We use the diagnostic plot to evaluate the appropriateness of the estimates obtained by CisGenome, NCIS and CCAT on several real data examples. Moreover, we show the impact that the choice of the normalization constant can have on standard tools for peak calling such as MACS or SICER. Finally, we propose a novel procedure for controlling the FDR using sample swapping. This procedure makes use of the estimated normalization constant in order to gain power over the naive choice of constant (used in MACS and SICER), which is the ratio of the total number of reads in the ChIP and Input samples. Linear normalization approaches aim to estimate a scale factor, r, to adjust for different sequencing depths when comparing ChIP versus Input samples. The estimated scaling factor can easily be incorporated in many peak caller algorithms to improve the accuracy of the peak identification. The diagnostic plot proposed in this paper can be used to assess how adequate ChIP/Input normalization constants are, and thus it allows the user to choose the most adequate estimate for the analysis.

Supernovae 2016bdu and 2005gl, and their link with SN 2009ip-like transients: another piece of the puzzle

NASA Astrophysics Data System (ADS)

Pastorello, A.; Kochanek, C. S.; Fraser, M.; Dong, Subo; Elias-Rosa, N.; Filippenko, A. V.; Benetti, S.; Cappellaro, E.; Tomasella, L.; Drake, A. J.; Harmanen, J.; Reynolds, T.; Shappee, B. J.; Smartt, S. J.; Chambers, K. C.; Huber, M. E.; Smith, K.; Stanek, K. Z.; Christensen, E. J.; Denneau, L.; Djorgovski, S. G.; Flewelling, H.; Gall, C.; Gal-Yam, A.; Geier, S.; Heinze, A.; Holoien, T. W.-S.; Isern, J.; Kangas, T.; Kankare, E.; Koff, R. A.; Llapasset, J.-M.; Lowe, T. B.; Lundqvist, P.; Magnier, E. A.; Mattila, S.; Morales-Garoffolo, A.; Mutel, R.; Nicolas, J.; Ochner, P.; Ofek, E. O.; Prosperi, E.; Rest, A.; Sano, Y.; Stalder, B.; Stritzinger, M. D.; Taddia, F.; Terreran, G.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.; Weiland, H.; Willman, M.; Young, D. R.; Zheng, W.

2018-02-01

Supernova (SN) 2016bdu is an unusual transient resembling SN 2009ip. SN 2009ip-like events are characterized by a long-lasting phase of erratic variability which ends with two luminous outbursts a few weeks apart. The second outburst is significantly more luminous (about 3 mag) than the first. In the case of SN 2016bdu, the first outburst (Event A) reached an absolute magnitude M(r) ~ -15.3 mag, while the second one (Event B) occurred over one month later and reached M(r) ~ -18 mag. By inspecting archival data, a faint source at the position of SN 2016bdu is detectable several times in the past few years. We interpret these detections as signatures of a phase of erratic variability, similar to that experienced by SN 2009ip between 2008 and mid-2012, and resembling the currently observed variability of the luminous blue variable SN 2000ch in NGC 3432. Spectroscopic monitoring of SN 2016bdu during the second peak initially shows features typical of a SN IIn. One month after the Event B maximum, the spectra develop broad Balmer lines with P Cygni profiles and broad metal features. At these late phases, the spectra resemble those of a typical Type II SN. All members of this SN 2009ip-like group are remarkably similar to the Type IIn SN 2005gl. For this object, the claim of a terminal SN explosion is supported by the disappearance of the progenitor star. The similarity with SN 2005gl suggests that all members of this family may finally explode as genuine SNe, although the unequivocal detection of nucleosynthesised elements in their nebular spectra is still missing.

The molecular topography of silenced chromatin in Saccharomyces cerevisiae

PubMed Central

Thurtle, Deborah M.; Rine, Jasper

2014-01-01

Heterochromatin imparts regional, promoter-independent repression of genes and is epigenetically heritable. Understanding how silencing achieves this regional repression is a fundamental problem in genetics and development. Current models of yeast silencing posit that Sir proteins, recruited by transcription factors bound to the silencers, spread throughout the silenced region. To test this model directly at high resolution, we probed the silenced chromatin architecture by chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq) of Sir proteins, histones, and a key histone modification, H4K16-acetyl. These analyses revealed that Sir proteins are strikingly concentrated at and immediately adjacent to the silencers, with lower levels of enrichment over the promoters at HML and HMR, the critical targets for transcriptional repression. The telomeres also showed discrete peaks of Sir enrichment yet a continuous domain of hypoacetylated histone H4K16. Surprisingly, ChIP-seq of cross-linked chromatin revealed a distribution of nucleosomes at silenced loci that was similar to Sir proteins, whereas native nucleosome maps showed a regular distribution throughout silenced loci, indicating that cross-linking captured a specialized chromatin organization imposed by Sir proteins. This specialized chromatin architecture observed in yeast informs the importance of a steric contribution to regional repression in other organisms. PMID:24493645

Argo_CUDA: Exhaustive GPU based approach for motif discovery in large DNA datasets.

PubMed

Vishnevsky, Oleg V; Bocharnikov, Andrey V; Kolchanov, Nikolay A

2018-02-01

The development of chromatin immunoprecipitation sequencing (ChIP-seq) technology has revolutionized the genetic analysis of the basic mechanisms underlying transcription regulation and led to accumulation of information about a huge amount of DNA sequences. There are a lot of web services which are currently available for de novo motif discovery in datasets containing information about DNA/protein binding. An enormous motif diversity makes their finding challenging. In order to avoid the difficulties, researchers use different stochastic approaches. Unfortunately, the efficiency of the motif discovery programs dramatically declines with the query set size increase. This leads to the fact that only a fraction of top "peak" ChIP-Seq segments can be analyzed or the area of analysis should be narrowed. Thus, the motif discovery in massive datasets remains a challenging issue. Argo_Compute Unified Device Architecture (CUDA) web service is designed to process the massive DNA data. It is a program for the detection of degenerate oligonucleotide motifs of fixed length written in 15-letter IUPAC code. Argo_CUDA is a full-exhaustive approach based on the high-performance GPU technologies. Compared with the existing motif discovery web services, Argo_CUDA shows good prediction quality on simulated sets. The analysis of ChIP-Seq sequences revealed the motifs which correspond to known transcription factor binding sites.

ReMap 2018: an updated atlas of regulatory regions from an integrative analysis of DNA-binding ChIP-seq experiments

PubMed Central

Chèneby, Jeanne; Gheorghe, Marius; Artufel, Marie

2018-01-01

Abstract With this latest release of ReMap (http://remap.cisreg.eu), we present a unique collection of regulatory regions in human, as a result of a large-scale integrative analysis of ChIP-seq experiments for hundreds of transcriptional regulators (TRs) such as transcription factors, transcriptional co-activators and chromatin regulators. In 2015, we introduced the ReMap database to capture the genome regulatory space by integrating public ChIP-seq datasets, covering 237 TRs across 13 million (M) peaks. In this release, we have extended this catalog to constitute a unique collection of regulatory regions. Specifically, we have collected, analyzed and retained after quality control a total of 2829 ChIP-seq datasets available from public sources, covering a total of 485 TRs with a catalog of 80M peaks. Additionally, the updated database includes new search features for TR names as well as aliases, including cell line names and the ability to navigate the data directly within genome browsers via public track hubs. Finally, full access to this catalog is available online together with a TR binding enrichment analysis tool. ReMap 2018 provides a significant update of the ReMap database, providing an in depth view of the complexity of the regulatory landscape in human. PMID:29126285

Classification of Small Negative Lightning Reports at the KSC-ER

NASA Technical Reports Server (NTRS)

Ward, Jennifer G.; Cummins, Kenneth L.; Krider, Philip

2008-01-01

The NASA Kennedy Space Center (KSC) and Air Force Eastern Range (ER) operate an extensive suite of lightning sensors because Florida experiences the highest area density of ground strikes in the United States, with area densities approaching 16 fl/sq km/yr when accumulated in 10x10 km (100 sq km) grids. The KSC-ER use data derived from two cloud-to-ground (CG) lightning detection networks, the "Cloud-to-Ground Lightning Surveillance System" (CGLSS) and the U.S. National Lightning Detection Network (TradeMark) (NLDN) plus a 3-dimensional lightning mapping system, the Lightning Detection and Ranging (LDAR) system, to provide warnings for ground operations and to insure mission safety during space launches. For operational applications at the KSC-ER it is important to understand the performance of each lightning detection system in considerable detail. In this work we examine a specific subset of the CGLSS stroke reports that have low values of the negative inferred peak current, Ip, i.e. values between 0 and -7 kA, and were thought to produce a new ground contact (NGC). When possible, the NLDN and LDAR systems were used to validate the CGLSS classification and to determine how many of these reported strokes were first strokes, subsequent strokes in a pre-existing channel (PEC), or cloud pulses that the CGLSS misclassified as CG strokes. It is scientifically important to determine the smallest current that can reach the ground either in the form of a first stroke or by way of a subsequent stroke that creates a new ground contact. In Biagi et al (2007), 52 low amplitude, negative return strokes ([Ip] < or = 10 kA) were evaluated in southern Arizona, northern Texas, and southern Oklahoma. The authors found that 50-87% of the small NLDN reports could be classified as CG (either first or subsequent strokes) on the basis of video and waveform recordings. Low amplitude return strokes are interesting because they are usually difficult to detect, and they are thought to bypass conventional lightning protection that relies on a sufficient attractive radius to prevent "shielding failure" (Golde, 1977). They also have larger location errors compared to the larger current events. In this study, we use the estimated peak current provided by the CGLSS and the results of our classification to determine the minimum Ip for each category of CG stroke and its probability of occurrence. Where possible, these results are compared to the findings in the literature.

Overview of Initial NSTX-U Experimental Operations

NASA Astrophysics Data System (ADS)

Battaglia, Devon; the NSTX-U Team

2016-10-01

Initial operation of the National Spherical Torus Experiment Upgrade (NSTX-U) has satisfied a number of commissioning milestones, including demonstration of discharges that exceed the field and pulse length of NSTX. ELMy H-mode operation at the no-wall βN limit is obtained with Boronized wall conditioning. Peak H-mode parameters include: Ip = 1 MA, BT0 = 0.63 T, WMHD = 330 kJ, βN = 4, βN/li = 6, κ = 2.3, τE , tot >50 ms. Access to high-performance H-mode scenarios with long MHD-quiescent periods is enabled by the resilient timing of the L-H transition via feedback control of the diverting time and shape, and correction of the dominant n =1 error fields during the Ip ramp. Stationary L-mode discharges have been realized up to 1 MA with 2 s discharges achieved at Ip = 650 kA. The long-pulse L-mode discharges enabled by the new central solenoid supported initial experiments on error field measurements and correction, plasma shape control, controlled discharge ramp-down, L-mode transport and fast ion physics. Increased off-axis current drive and reduction of fast ion instabilities has been observed with the new, more tangential neutral beamline. The initial results support that access to increased field, current and heating at low-aspect-ratio expands the regimes available to develop scenarios, diagnostics and predictive models that inform the design and optimization of future burning plasma tokamak devices, including ITER. Work Supported by U.S. DOE Contract No. DE-AC02-09CH11466.

MULTI-SPACECRAFT ANALYSIS OF ENERGETIC HEAVY ION AND INTERPLANETARY SHOCK PROPERTIES IN ENERGETIC STORM PARTICLE EVENTS NEAR 1 au

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebert, R. W.; Dayeh, M. A.; Desai, M. I.

2016-11-10

We examine the longitude distribution of and relationship between interplanetary (IP) shock properties and ∼0.1–20 MeV nucleon{sup -1} O and Fe ions during seven multi-spacecraft energetic storm particle (ESP) events at 1 au. These ESP events were observed at two spacecraft and were primarily associated with low Mach number, quasi-perpendicular shocks. Key observations include the following: (i) the Alfvén Mach number increased from east to west of the coronal mass ejection source longitude, while the shock speed, compression ratios, and obliquity showed no clear dependence; (ii) the O and Fe time intensity profiles and peak intensities varied significantly between longitudinallymore » separated spacecraft observing the same event, the peak intensities being larger near the nose and smaller along the flank of the IP shock; (iii) the O and Fe peak intensities had weak to no correlations with the shock parameters; (iv) the Fe/O time profiles showed intra-event variations upstream of the shock that disappeared downstream of the shock, where values plateaued to those comparable to the mean Fe/O of solar cycle 23; (v) the O and Fe spectral index ranged from ∼1.0 to 3.4, the Fe spectra being softer in most events; and (vi) the observed spectral index was softer than the value predicted from the shock compression ratio in most events. We conclude that while the variations in IP shock properties may account for some variations in O and Fe properties within these multi-spacecraft events, detailed examination of the upstream seed population and IP turbulence, along with modeling, are required to fully characterize these observations.« less

Reusable, extensible, and modifiable R scripts and Kepler workflows for comprehensive single set ChIP-seq analysis.

PubMed

Cormier, Nathan; Kolisnik, Tyler; Bieda, Mark

2016-07-05

There has been an enormous expansion of use of chromatin immunoprecipitation followed by sequencing (ChIP-seq) technologies. Analysis of large-scale ChIP-seq datasets involves a complex series of steps and production of several specialized graphical outputs. A number of systems have emphasized custom development of ChIP-seq pipelines. These systems are primarily based on custom programming of a single, complex pipeline or supply libraries of modules and do not produce the full range of outputs commonly produced for ChIP-seq datasets. It is desirable to have more comprehensive pipelines, in particular ones addressing common metadata tasks, such as pathway analysis, and pipelines producing standard complex graphical outputs. It is advantageous if these are highly modular systems, available as both turnkey pipelines and individual modules, that are easily comprehensible, modifiable and extensible to allow rapid alteration in response to new analysis developments in this growing area. Furthermore, it is advantageous if these pipelines allow data provenance tracking. We present a set of 20 ChIP-seq analysis software modules implemented in the Kepler workflow system; most (18/20) were also implemented as standalone, fully functional R scripts. The set consists of four full turnkey pipelines and 16 component modules. The turnkey pipelines in Kepler allow data provenance tracking. Implementation emphasized use of common R packages and widely-used external tools (e.g., MACS for peak finding), along with custom programming. This software presents comprehensive solutions and easily repurposed code blocks for ChIP-seq analysis and pipeline creation. Tasks include mapping raw reads, peakfinding via MACS, summary statistics, peak location statistics, summary plots centered on the transcription start site (TSS), gene ontology, pathway analysis, and de novo motif finding, among others. These pipelines range from those performing a single task to those performing full analyses of ChIP-seq data. The pipelines are supplied as both Kepler workflows, which allow data provenance tracking, and, in the majority of cases, as standalone R scripts. These pipelines are designed for ease of modification and repurposing.

Different signaling pathway between sphingosine-1-phosphate and lysophosphatidic acid in Xenopus oocytes: functional coupling of the sphingosine-1-phosphate receptor to PLC-xbeta in Xenopus oocytes.

PubMed

Noh, S J; Kim, M J; Shim, S; Han, J K

1998-08-01

In Xenopus oocytes, both sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) activate Ca2+-dependent oscillatory Cl- currents by acting through membrane-bound receptors. External application of 50 microM S1P elicited a long-lasting oscillatory current that continued over 30 min from the beginning of oscillation, with 300 nA (n = 11) as a usual maximum peak of current, whereas 1-microM LPA treatment showed only transiently oscillating but more vigorous current responses, with 2,800 nA (n = 18) as a maximum peak amplitude. Both phospholipid-induced Ca2+-dependent Cl- currents were observed in the absence of extracellular Ca2+, were blocked by intracellular injection of the Ca2+ chelator, EGTA, and could not be elicited by treatment with thapsigargin, an inhibitor of endoplasmic reticulum (ER) Ca2+ ATPase. Intracellular Ca2+ release appeared to be from inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store, because Cl- currents were blocked by heparin injection. Pretreatment with the aminosteroid, U-73122, an inhibitor of G protein-mediated phospholipase C (PLC) activation, to oocytes inhibited the current responses evoked both by S1P and LPA. However, when they were injected with 10 ng of antisense oligonucleotide (AS-ODN) against Xenopus phospholipase C (PLC-xbeta), oocytes could not respond to S1P application, whereas they responded normally to LPA, indicating that the S1P signaling pathway goes through PLC-xbeta, whereas LPA signaling goes through another unknown PLC. To determine the types of G proteins involved, we introduced AS-ODNs against four types of G-protein alpha subunits that were identified in Xenopus laevis; G(q)alpha, G11alpha, G0alpha, and G(i1)alpha. Among AS-ODNs against the G alphas tested, AS-G(q)alpha and AS-G(i1)alpha to S1P and AS-G(q)alpha and AS-G11alpha to LPA specifically reduced current responses, respectively, to about 20-30% of controls. These results demonstrate that LPA and S1P, although they have similar structural features, release intracellular Ca2+ from the IP3-sensitive pool, use different components in their signal transduction pathways in Xenopus oocytes.

Determination of the ionization potentials of security-relevant substances with single photon ionization mass spectrometry using synchrotron radiation.

PubMed

Schramm, E; Mühlberger, F; Mitschke, S; Reichardt, G; Schulte-Ladbeck, R; Pütz, M; Zimmermann, R

2008-02-01

Several ionization potentials (IPs) of security relevant substances were determined with single photon ionization time of flight mass spectrometry (SPI-TOFMS) using monochromatized synchrotron radiation from the "Berliner Elektronenspeicherring-Gesellschaft für Synchrotronstrahlung" (BESSY). In detail, the IPs of nine explosives and related compounds, seven narcotics and narcotics precursors, and one chemical warfare agent (CWA) precursor were determined, whereas six IPs already known from the literature were verified correctly. From seven other substances, including one CWA precursor, the IP could not be determined as the molecule ion peak could not be detected. For these substances the appearance energy (AE) of a main fragment was determined. The analyzed security-relevant substances showed IPs significantly below the IPs of common matrix compounds such as nitrogen and oxygen. Therefore, it is possible to find photon energies in between, whereby the molecules of interest can be detected with SPI in very low concentrations due to the shielding of the matrix. All determined IPs except the one of the explosive EGDN were below 10.5 eV. Hence, laser-generated 118 nm photons can be applied for detecting almost all security-relevant substances by, e.g., SPI-TOFMS.

A demonstration of the H3 trimethylation ChIP-seq analysis of galline follicular mesenchymal cells and male germ cells.

PubMed

Chokeshaiusaha, Kaj; Puthier, Denis; Nguyen, Catherine; Sananmuang, Thanida

2018-06-01

Trimethylation of histone 3 (H3) at 4th lysine N-termini (H3K4me3) in gene promoter region was the universal marker of active genes specific to cell lineage. On the contrary, coexistence of trimethylation at 27th lysine (H3K27me3) in the same loci-the bivalent H3K4m3/H3K27me3 was known to suspend the gene transcription in germ cells, and could also be inherited to the developed stem cell. In galline species, throughout example of H3K4m3 and H3K27me3 ChIP-seq analysis was still not provided. We therefore designed and demonstrated such procedures using ChIP-seq and mRNA-seq data of chicken follicular mesenchymal cells and male germ cells. Analytical workflow was designed and provided in this study. ChIP-seq and RNA-seq datasets of follicular mesenchymal cells and male germ cells were acquired and properly preprocessed. Peak calling by Model-based analysis of ChIP-seq 2 was performed to identify H3K4m3 or H3K27me3 enriched regions (Fold-change≥2, FDR≤0.01) in gene promoter regions. Integrative genomics viewer was utilized for cellular retinoic acid binding protein 1 ( CRABP1 ), growth differentiation factor 10 ( GDF10 ), and gremlin 1 ( GREM1 ) gene explorations. The acquired results indicated that follicular mesenchymal cells and germ cells shared several unique gene promoter regions enriched with H3K4me3 (5,704 peaks) and also unique regions of bivalent H3K4m3/H3K27me3 shared between all cell types and germ cells (1,909 peaks). Subsequent observation of follicular mesenchyme-specific genes- CRABP1 , GDF10 , and GREM1 correctly revealed vigorous transcriptions of these genes in follicular mesenchymal cells. As expected, bivalent H3K4m3/H3K27me3 pattern was manifested in gene promoter regions of germ cells, and thus suspended their transcriptions. According the results, an example of chicken H3K4m3/H3K27me3 ChIP-seq data analysis was successfully demonstrated in this study. Hopefully, the provided methodology should hereby be useful for galline ChIP-seq data analysis in the future.

Auxiliary KChIP4a Suppresses A-type K+ Current through Endoplasmic Reticulum (ER) Retention and Promoting Closed-state Inactivation of Kv4 Channels*

PubMed Central

Tang, Yi-Quan; Liang, Ping; Zhou, Jingheng; Lu, Yanxin; Lei, Lei; Bian, Xiling; Wang, KeWei

2013-01-01

In the brain and heart, auxiliary Kv channel-interacting proteins (KChIPs) co-assemble with pore-forming Kv4 α-subunits to form a native K+ channel complex and regulate the expression and gating properties of Kv4 currents. Among the KChIP1–4 members, KChIP4a exhibits a unique N terminus that is known to suppress Kv4 function, but the underlying mechanism of Kv4 inhibition remains unknown. Using a combination of confocal imaging, surface biotinylation, and electrophysiological recordings, we identified a novel endoplasmic reticulum (ER) retention motif, consisting of six hydrophobic and aliphatic residues, 12–17 (LIVIVL), within the KChIP4a N-terminal KID, that functions to reduce surface expression of Kv4-KChIP complexes. This ER retention capacity is transferable and depends on its flanking location. In addition, adjacent to the ER retention motif, the residues 19–21 (VKL motif) directly promote closed-state inactivation of Kv4.3, thus leading to an inhibition of channel current. Taken together, our findings demonstrate that KChIP4a suppresses A-type Kv4 current via ER retention and enhancement of Kv4 closed-state inactivation. PMID:23576435

Auxiliary KChIP4a suppresses A-type K+ current through endoplasmic reticulum (ER) retention and promoting closed-state inactivation of Kv4 channels.

PubMed

Tang, Yi-Quan; Liang, Ping; Zhou, Jingheng; Lu, Yanxin; Lei, Lei; Bian, Xiling; Wang, KeWei

2013-05-24

In the brain and heart, auxiliary Kv channel-interacting proteins (KChIPs) co-assemble with pore-forming Kv4 α-subunits to form a native K(+) channel complex and regulate the expression and gating properties of Kv4 currents. Among the KChIP1-4 members, KChIP4a exhibits a unique N terminus that is known to suppress Kv4 function, but the underlying mechanism of Kv4 inhibition remains unknown. Using a combination of confocal imaging, surface biotinylation, and electrophysiological recordings, we identified a novel endoplasmic reticulum (ER) retention motif, consisting of six hydrophobic and aliphatic residues, 12-17 (LIVIVL), within the KChIP4a N-terminal KID, that functions to reduce surface expression of Kv4-KChIP complexes. This ER retention capacity is transferable and depends on its flanking location. In addition, adjacent to the ER retention motif, the residues 19-21 (VKL motif) directly promote closed-state inactivation of Kv4.3, thus leading to an inhibition of channel current. Taken together, our findings demonstrate that KChIP4a suppresses A-type Kv4 current via ER retention and enhancement of Kv4 closed-state inactivation.

The Physics of Local Helicity Injection Non-Solenoidal Tokamak Startup

NASA Astrophysics Data System (ADS)

Redd, A. J.; Barr, J. L.; Bongard, M. W.; Fonck, R. J.; Hinson, E. T.; Jardin, S.

2013-10-01

Non-solenoidal startup via Local Helicity Injection (LHI) uses compact current injectors to produce toroidal plasma current Ip up to 170 kA in the PEGASUS Toroidal Experiment, driven by 4-8 kA injector current on timescales of 5-20 milliseconds. Increasing the Ip buildup duration enables experimental demonstration of plasma position control on timescales relevant for high-current startup. LHI-driven discharges exhibit bursty MHD activity, apparently line-tied kinking of LHI-driven field lines, with the bursts correlating with rapid equilibrium changes, sharp Ip rises, and sharp drops in the injector impedance. Preliminary NIMROD results suggest that helical LHI-driven current channels remain coherent, with Ip increases due to reconnection between adjacent helical turns forming axisymmetric plasmoids, and corresponding sharp drops in the bias circuit impedance. The DC injector impedance is consistent with a space charge limit at low bias current and a magnetic limit at high bias current. Internal measurements show the current density profile starts strongly hollow and rapidly fills in during Ip buildup. Simulations of LHI discharges using the Tokamak Simulation Code (TSC) will provide insight into the detailed current drive mechanism and guide experiments on PEFASUS and NSTX-U. Work supported by US DOE Grants DE-FG02-96ER54375 and DE-SC0006928.

Motif-based analysis of large nucleotide data sets using MEME-ChIP

PubMed Central

Ma, Wenxiu; Noble, William S; Bailey, Timothy L

2014-01-01

MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets. It can analyze peak regions identified by ChIP-seq, cross-linking sites identified by cLIP-seq and related assays, as well as sets of genomic regions selected using other criteria. MEME-ChIP performs de novo motif discovery, motif enrichment analysis, motif location analysis and motif clustering, providing a comprehensive picture of the DNA or RNA motifs that are enriched in the input sequences. MEME-ChIP performs two complementary types of de novo motif discovery: weight matrix–based discovery for high accuracy; and word-based discovery for high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human, mouse, worm, fly and other model organisms provides even greater sensitivity. MEME-ChIP’s interactive HTML output groups and aligns significant motifs to ease interpretation. this protocol takes less than 3 h, and it provides motif discovery approaches that are distinct and complementary to other online methods. PMID:24853928

Interferon gamma-inducible protein-10 (IP-10) and eotaxin as biomarkers in age-related macular degeneration.

PubMed

Mo, Fong Ming; Proia, Alan D; Johnson, Walter H; Cyr, Desiree; Lashkari, Kameran

2010-08-01

To analyze serum cytokine levels in subjects with different stages of AMD and to study the expression of salient cytokines in postmortem eyes with AMD. A suspension array system was used to analyze sera (n = 18 to 20/group) from control subjects and those with early AMD (AREDS stage 1), intermediate dry AMD (AREDS stage 3), advanced AMD with geographic atrophy (GA), or neovascular AMD (CNV). Postmortem eyes with AMD or control eyes were examined immunohistochemically for expression of IP-10 and eotaxin (n = 4 to 8/group). Serum eotaxin and IP-10 levels were significantly elevated in all stages of AMD, except for eotaxin levels in neovascular AMD (P < 0.07). The peak of serum IP-10 concentration was at intermediate dry AMD. In donor eyes, IP-10 and eotaxin expressions were increased in the RPE of eyes with early AMD, GA, and CNV. Eotaxin accumulated within the layer of basal linear/laminar deposits in all stages of AMD, while IP-10 was mainly in eyes with GA and CNV. IP-10 was abundant in the connective tissue matrix associated with CNV, and eotaxin was usually present but more focally and with less intense staining. Both IP-10 and eotaxin were expressed by neovascular endothelial cells. Both IP-10 and eotaxin were expressed in the neurosensory retina, but there was no detectable difference in staining between eyes with or without AMD. IP-10 and eotaxin may be early biomarkers in AMD. The authors hypothesize that the relative balance between levels of IP-10 and eotaxin is critical in regulating the neovascular response.

Scrape-off-layer currents during MHD activity and disruptions in HBT-EP

NASA Astrophysics Data System (ADS)

Levesque, J. P.; Desanto, S.; Battey, A.; Bialek, J.; Brooks, J. W.; Mauel, M. E.; Navratil, G. A.

2017-10-01

We report scrape-off layer (SOL) current measurements during MHD mode activity and disruptions in the HBT-EP tokamak. Currents are measured via Rogowski coils mounted on tiles in the low-field-side SOL, toroidal jumpers between otherwise-isolated vessel sections, and segmented plasma current Rogowski coils. These currents strongly depend on the plasma's major radius, mode amplitude, and mode phase. Plasma current asymmetries and SOL currents during disruptions reach 4% of the plasma current. Asymmetric toroidal currents between vessel sections rotate at tens of kHz through most of the current quench, then symmetrize once Ip reaches 30% of its pre-disruptive value. Toroidal jumper currents oscillate between co- and counter-Ip, with co-Ip being dominant on average during disruptions. Increases in local plasma current correlate with counter-Ip current in the nearest toroidal jumper. Measurements are interpreted in the context of two models that produce contrary predictions for the toroidal vessel current polarity during disruptions. Plasma current asymmetries are consistent with both models, and scale with plasma displacement toward the wall. Progress of ongoing SOL current diagnostic upgrades is also presented. Supported by U.S. DOE Grant DE-FG02-86ER53222.

ReMap 2018: an updated atlas of regulatory regions from an integrative analysis of DNA-binding ChIP-seq experiments.

PubMed

Chèneby, Jeanne; Gheorghe, Marius; Artufel, Marie; Mathelier, Anthony; Ballester, Benoit

2018-01-04

With this latest release of ReMap (http://remap.cisreg.eu), we present a unique collection of regulatory regions in human, as a result of a large-scale integrative analysis of ChIP-seq experiments for hundreds of transcriptional regulators (TRs) such as transcription factors, transcriptional co-activators and chromatin regulators. In 2015, we introduced the ReMap database to capture the genome regulatory space by integrating public ChIP-seq datasets, covering 237 TRs across 13 million (M) peaks. In this release, we have extended this catalog to constitute a unique collection of regulatory regions. Specifically, we have collected, analyzed and retained after quality control a total of 2829 ChIP-seq datasets available from public sources, covering a total of 485 TRs with a catalog of 80M peaks. Additionally, the updated database includes new search features for TR names as well as aliases, including cell line names and the ability to navigate the data directly within genome browsers via public track hubs. Finally, full access to this catalog is available online together with a TR binding enrichment analysis tool. ReMap 2018 provides a significant update of the ReMap database, providing an in depth view of the complexity of the regulatory landscape in human. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Modulation of A-type potassium channels by a family of calcium sensors.

PubMed

An, W F; Bowlby, M R; Betty, M; Cao, J; Ling, H P; Mendoza, G; Hinson, J W; Mattsson, K I; Strassle, B W; Trimmer, J S; Rhodes, K J

2000-02-03

In the brain and heart, rapidly inactivating (A-type) voltage-gated potassium (Kv) currents operate at subthreshold membrane potentials to control the excitability of neurons and cardiac myocytes. Although pore-forming alpha-subunits of the Kv4, or Shal-related, channel family form A-type currents in heterologous cells, these differ significantly from native A-type currents. Here we describe three Kv channel-interacting proteins (KChIPs) that bind to the cytoplasmic amino termini of Kv4 alpha-subunits. We find that expression of KChIP and Kv4 together reconstitutes several features of native A-type currents by modulating the density, inactivation kinetics and rate of recovery from inactivation of Kv4 channels in heterologous cells. All three KChIPs co-localize and co-immunoprecipitate with brain Kv4 alpha-subunits, and are thus integral components of native Kv4 channel complexes. The KChIPs have four EF-hand-like domains and bind calcium ions. As the activity and density of neuronal A-type currents tightly control responses to excitatory synaptic inputs, these KChIPs may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium.

Gut satiety hormones cholecystokinin and glucagon-like Peptide-17-36 amide mediate anorexia induction by trichothecenes T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol.

PubMed

Zhang, Jie; Liu, Shengli; Zhang, Hua; Li, Yuanyuan; Wu, Wenda; Zhang, Haibin

2017-11-15

The food-borne trichothecene mycotoxins have been documented to cause human and animal food poisoning. Anorexia is a hallmark of the trichothecene mycotoxins-induced adverse effects. Type B trichothecenes have been previously demonstrated to elicit robust anorectic responses, and this response has been directly linked to secretion of the gut satiety hormones cholecystokinin (CCK) and glucagon-like peptide-1 7-36 amide (GLP-1). However, less is known about the anorectic effects and underlying mechanisms of the type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), neosolaniol (NEO). The purpose of this study was to relate type A trichothecenes T-2, HT-2, DAS and NEO-induced anorectic response to changes plasma concentrations of CCK and GLP-1. Following both oral gavage and intraperitoneal (IP) administration of 1mg/kg bw T-2, HT-2, DAS and NEO evoked robust anorectic response and secretion of CCK and GLP-1. Elevations of plasma CCK markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Following oral exposure, plasma CCK was peaked at 6h, 6h, 2h, 2h and lasted up to 24h, 24h, > 6h, > 6h for T-2, HT-2, DAS and NEO, respectively. IP exposed to four toxins all induced elevation of CCK with peak point and duration at 6h and >24h, respectively. In contrast to CCK, GLP-1 was moderately elevated by these toxins. Following both oral and IP exposure, T-2 and HT-2 evoked plasma GLP-1 elevation with peak point and duration at 2h and 6h, respectively. Plasma GLP-1 was peaked at 2h and still increased at 6h for IP and oral administration with DAS and NEO, respectively. In conclusion, CCK plays a contributory role in anorexia induction but GLP-1 might play a lesser role in this response. Copyright © 2017 Elsevier Inc. All rights reserved.

An elevation in physical coupling of type 1 inositol 1,4,5-trisphosphate (IP3) receptors to transient receptor potential 3 (TRPC3) channels constricts mesenteric arteries in genetic hypertension.

PubMed

Adebiyi, Adebowale; Thomas-Gatewood, Candice M; Leo, M Dennis; Kidd, Michael W; Neeb, Zachary P; Jaggar, Jonathan H

2012-11-01

Hypertension is associated with an elevation in agonist-induced vasoconstriction, but mechanisms involved require further investigation. Many vasoconstrictors bind to phospholipase C-coupled receptors, leading to an elevation in inositol 1,4,5-trisphosphate (IP(3)) that activates sarcoplasmic reticulum IP(3) receptors. In cerebral artery myocytes, IP(3) receptors release sarcoplasmic reticulum Ca(2+) and can physically couple to canonical transient receptor potential 3 (TRPC3) channels in a caveolin-1-containing macromolecular complex, leading to cation current activation that stimulates vasoconstriction. Here, we investigated mechanisms by which IP(3) receptors control vascular contractility in systemic arteries and IP(3)R involvement in elevated agonist-induced vasoconstriction during hypertension. Total and plasma membrane-localized TRPC3 protein was ≈2.7- and 2-fold higher in mesenteric arteries of spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto (WKY) rat controls, respectively. In contrast, IP(3)R1, TRPC1, TRPC6, and caveolin-1 expression was similar. TRPC3 expression was also similar in arteries of pre-SHRs and WKY rats. Control, IP(3)-induced and endothelin-1 (ET-1)-induced fluorescence resonance energy transfer between IP3R1 and TRPC3 was higher in SHR than WKY myocytes. IP3-induced cation current was ≈3-fold larger in SHR myocytes. Pyr3, a selective TRPC3 channel blocker, and calmodulin and IP(3) receptor binding domain peptide, an IP(3)R-TRP physical coupling inhibitor, reduced IP(3)-induced cation current and ET-1-induced vasoconstriction more in SHR than WKY myocytes and arteries. Thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase blocker, did not alter ET-1-stimulated vasoconstriction in SHR or WKY arteries. These data indicate that ET-1 stimulates physical coupling of IP(3)R1 to TRPC3 channels in mesenteric artery myocytes, leading to vasoconstriction. Furthermore, an elevation in IP(3)R1 to TRPC3 channel molecular coupling augments ET-1-induced vasoconstriction during hypertension.

ChIP-PaM: an algorithm to identify protein-DNA interaction using ChIP-Seq data.

PubMed

Wu, Song; Wang, Jianmin; Zhao, Wei; Pounds, Stanley; Cheng, Cheng

2010-06-03

ChIP-Seq is a powerful tool for identifying the interaction between genomic regulators and their bound DNAs, especially for locating transcription factor binding sites. However, high cost and high rate of false discovery of transcription factor binding sites identified from ChIP-Seq data significantly limit its application. Here we report a new algorithm, ChIP-PaM, for identifying transcription factor target regions in ChIP-Seq datasets. This algorithm makes full use of a protein-DNA binding pattern by capitalizing on three lines of evidence: 1) the tag count modelling at the peak position, 2) pattern matching of a specific tag count distribution, and 3) motif searching along the genome. A novel data-based two-step eFDR procedure is proposed to integrate the three lines of evidence to determine significantly enriched regions. Our algorithm requires no technical controls and efficiently discriminates falsely enriched regions from regions enriched by true transcription factor (TF) binding on the basis of ChIP-Seq data only. An analysis of real genomic data is presented to demonstrate our method. In a comparison with other existing methods, we found that our algorithm provides more accurate binding site discovery while maintaining comparable statistical power.

Dependence of Na+ pump current on external monovalent cations and membrane potential in rabbit cardiac Purkinje cells.

PubMed Central

Bielen, F V; Glitsch, H G; Verdonck, F

1991-01-01

1. The effect of membrane potential and various extracellular monovalent cations on the Na+ pump current (Ip) was studied on isolated, single Purkinje cells of the rabbit heart by means of whole-cell recording. 2. Ip was identified as current activated by external K+ or its congeners NH4+ and Tl+. The current was blocked by dihydroouabain (1-5 x 10(-4) M) over the whole range of membrane potentials tested. 3. In Na(+)-containing solution half-maximum Ip activation (K0.5) occurred at 0.4 mM-Tl+, 1.9 mM-K+ and 5.7 mM-NH4+ (holding potential, -20 mV). 4. The pump current (Ip)-voltage (V) relationship of the cells in Na(+)-containing media with K+ or its congeners at the tested concentrations greater than K0.5 displayed a steep positive slope at negative membrane potentials between -120 and -20 mV. Little voltage dependence of Ip was observed at more positive potentials up to +40 mV. At even more positive potentials Ip measured at 2 and 5.4 mM-K+ decreased. 5. Lowering the concentration of K+ or its congeners below the K0.5 value in Na(+)-containing solution induced a region of negative slope of the Ip-V curve at membrane potentials positive to -20 mV. 6. The shape of the Ip-V relationship remained unchanged when the K+ concentration (5.4 mM) of the Na(+)-containing medium was replaced by NH4+ or Tl+ concentrations of similar potency to activate Ip (20 mM-NH4+ or 2 mM-Tl+). 7. In Na(+)-free, choline-containing solution half-maximum Ip activation occurred at 0.13 mM-K+ (holding potential, -20 mV). 8. At negative membrane potentials the positive slope of the Ip-V curve was flatter in Na(+)-free than in Na(+)-containing media. A reduced voltage dependence of Ip persisted, regardless of whether choline ions or Li+ were used as a Na+ substitute. 9. Lowering the K+ concentration of the Na(+)-free, choline-containing solution to 0.05 mM evoked an extended region of negative slope in the Ip-V relationship at membrane potentials between -40 and +60 mV. 10. It is concluded that the apparent affinity of the Na(+)-K+ pump towards K+ in cardiac Purkinje cells depends on both the membrane potential and the extracellular Na+ concentration. 11. The region of negative slope of the Ip-V curve observed in cells which were superfused with media containing low concentrations of K+ or its congeners strongly suggests the existence of at least two voltage-sensitive steps in the cardiac Na(+)-K+ pump cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1665855

R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models.

PubMed

Siddappa, Nagadenahalli B; Watkins, Jennifer D; Wassermann, Klemens J; Song, Ruijiang; Wang, Wendy; Kramer, Victor G; Lakhashe, Samir; Santosuosso, Michael; Poznansky, Mark C; Novembre, Francis J; Villinger, François; Else, James G; Montefiori, David C; Rasmussen, Robert A; Ruprecht, Ruth M

2010-07-21

HIV-1 clade C (HIV-C) predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb) responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1) HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2) phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models. We constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an "early," recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a "late" form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM) with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to "late" SHIV-1157ipd3N4 (tier 2). After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM. SHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.

Analysis of ChIP-seq Data in R/Bioconductor.

PubMed

de Santiago, Ines; Carroll, Thomas

2018-01-01

The development of novel high-throughput sequencing methods for ChIP (chromatin immunoprecipitation) has provided a very powerful tool to study gene regulation in multiple conditions at unprecedented resolution and scale. Proactive quality-control and appropriate data analysis techniques are of critical importance to extract the most meaningful results from the data. Over the last years, an array of R/Bioconductor tools has been developed allowing researchers to process and analyze ChIP-seq data. This chapter provides an overview of the methods available to analyze ChIP-seq data based primarily on software packages from the open-source Bioconductor project. Protocols described in this chapter cover basic steps including data alignment, peak calling, quality control and data visualization, as well as more complex methods such as the identification of differentially bound regions and functional analyses to annotate regulatory regions. The steps in the data analysis process were demonstrated on publicly available data sets and will serve as a demonstration of the computational procedures routinely used for the analysis of ChIP-seq data in R/Bioconductor, from which readers can construct their own analysis pipelines.

Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel complexes with ISA-like properties.

PubMed

Jerng, Henry H; Kunjilwar, Kumud; Pfaffinger, Paul J

2005-11-01

Kv4 pore-forming subunits are the principal constituents of the voltage-gated K+ channel underlying somatodendritic subthreshold A-type currents (I(SA)) in neurones. Two structurally distinct types of Kv4 channel modulators, Kv channel-interacting proteins (KChIPs) and dipeptidyl-peptidase-like proteins (DPLs: DPP6 or DPPX, DPP10 or DPPY), enhance surface expression and modify functional properties. Since KChIP and DPL distributions overlap in the brain, we investigated the potential coassembly of Kv4.2, KChIP3 and DPL proteins, and the contribution of DPLs to ternary complex properties. Immunoprecipitation results show that KChIP3 and DPP10 associate simultaneously with Kv4.2 proteins in rat brain as well as heterologously expressing Xenopus oocytes, indicating Kv4.2 + KChIP3 + DPP10 multiprotein complexes. Consistent with ternary complex formation, coexpression of Kv4.2, KChIP3 and DPP10 in oocytes and CHO cells results in current waveforms distinct from the arithmetic sum of Kv4.2 + KChIP3 and Kv4.2 + DPP10 currents. Furthermore, the Kv4.2 + KChIP3 + DPP10 channels recover from inactivation very rapidly (tau(rec) approximately 18-26 ms), closely matching that of native I(SA) and significantly faster than the recovery of Kv4.2 + KChIP3 or Kv4.2 + DPP10 channels. For comparison, identical triple coexpression experiments were performed using DPP6 variants. While most results are similar, the Kv4.2 + KChIP3 + DPP6 channels exhibit inactivation that slows with increasing membrane potential, resulting in inactivation slower than that of Kv4.2 + KChIP3 + DPP10 channels at positive voltages. In conclusion, the native neuronal subthreshold A-type channel is probably a macromolecular complex formed from Kv4 and a combination of both KChIP and DPL proteins, with the precise composition of channel alpha and auxiliary subunits underlying tissue and regional variability in I(SA) properties.

Sub-corotating region of Saturn's magnetosphere: Cassini observations of the azimuthal field and implications for the ionospheric Pederesen Current (Invited)

NASA Astrophysics Data System (ADS)

Smith, E. J.; Dougherty, M. K.; Zhou, X.

2010-12-01

A consensus model of Saturn’s magnetosphere that has broad acceptance consists of four regions in which the plasma and field are corotating, sub-corotating or undergoing Vasyliunas or Dungey convection. In this model, the sub-corotating magnetosphere contains a large scale circuital current system comprised of radial, field-aligned and ionospheric currents. A quantitative rendering of this system developed by S. Cowley and E. Bunch relates the azimuthal field component, B phi, that causes the field to spiral to the ionospheric Pedersen current , Ip. Cassini measurements of B phi over the four year interval between 2005 and 2008 that are widely distributed in radial distance, latitude and local time have been used to compute Ip from a Bunce-Cowley formula. A striking north-south asymmetry of the global magnetosphere has been found. In the southern hemisphere, the magnitude and variation of Ip with invariant colatitude, θ, agree qualitatively with the model but Ip (θ) is shifted poleward by about 10°. In the northern hemisphere, however, the data fail to reproduce the profile of Ip (θ) predicted by the model but are dominated by two high latitude currents having the wrong polarities. Possible causes of this asymmetry are seasonal variations (summer in the southern hemisphere) and/or asymmetric plasma outflow from the inner magnetosphere such as the plumes extending southward from Enceladus. Another finding is a significant local time dependence of Ip(θ) rather than the axisymmetry assumed in the model. There is a close correspondence with the model in the noon sector. The currents in the midnight and dawn sectors are significantly larger than in the noon sector and the current in the dusk sector is dramatically weaker.

Observation and analysis of halo current in EAST

NASA Astrophysics Data System (ADS)

Chen, Da-Long; Shen, Biao; Qian, Jin-Ping; Sun, You-Wen; Liu, Guang-Jun; Shi, Tong-Hui; Zhuang, Hui-Dong; Xiao, Bing-Jia

2014-06-01

Plasma in a typically elongated cross-section tokamak (for example, EAST) is inherently unstable against vertical displacement. When plasma loses the vertical position control, it moves downward or upward, leading to disruption, and a large halo current is generated helically in EAST typically in the scrape-off layer. When flowing into the vacuum vessel through in-vessel components, the halo current will give rise to a large J × B force acting on the vessel and the in-vessel components. In EAST VDE experiment, part of the eddy current is measured in halo sensors, due to the large loop voltage. Primary experimental data demonstrate that the halo current first lands on the outer plate and then flows clockwise, and the analysis of the information indicates that the maximum halo current estimated in EAST is about 0.4 times the plasma current and the maximum value of TPF × Ih/IP0 is 0.65, furthermore Ih/Ip0 and TPF × Ih/Ip0 tend to increase with the increase of Ip0. The test of the strong gas injection system shows good success in increasing the radiated power, which may be effective in reducing the halo current.

Circadian Behavioral Responses to Light and Optic Chiasm-Evoked Glutamatergic EPSCs in the Suprachiasmatic Nucleus of ipRGC Conditional vGlut2 Knock-Out Mice

PubMed Central

2018-01-01

Abstract Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator that functions as a biological clock. ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. Pituitary adenylate cyclase-activating polypeptide (PACAP) is also packaged into vesicles in ipRGCs and PACAP may be coreleased with glutamate in the SCN. vGlut2 has been conditionally deleted in ipRGCs in mice [conditional knock-outs (cKOs)] and their aberrant photoentrainment and residual attenuated light responses have been ascribed to ipRGC PACAP release. However, there is no direct evidence that all ipRGC glutamatergic neurotransmission is eliminated in vGlut2 cKOs. Here, we examined two lines of ipRGC vGlut2 cKO mice for SCN-mediated behavioral responses under several lighting conditions and for ipRGC glutamatergic neurotransmission in the SCN. Circadian behavioral responses varied from a very limited response to light to near normal photoentrainment. After collecting behavioral data, hypothalamic slices were prepared and evoked EPSCs (eEPSCs) were recorded from SCN neurons by stimulating the optic chiasm. In cKOs, glutamatergic eEPSCs were recorded and all eEPSC parameters examined (stimulus threshold, amplitude, rise time or time-to-peak and stimulus strength to evoke a maximal response) were similar to controls. We conclude that a variable number but functionally significant percentage of ipRGCs in two vGlut2 cKO mouse lines continue to release glutamate. Thus, the residual SCN-mediated light responses in these cKO mouse lines cannot be attributed solely to ipRGC PACAP release. PMID:29756029

Autocrine A2 in the T-System of Ventricular Myocytes Creates Transmural Gradients in Ion Transport: A Mechanism to Match Contraction with Load?

PubMed Central

Gao, Junyuan; Sun, Xiurong; Potapova, Irina A.; Cohen, Ira S.; Mathias, Richard T.; Kim, Jeremy H.

2014-01-01

Transmural heterogeneities in Na/K pump current (IP), transient outward K+-current (Ito), and Ca2+-current (ICaL) play an important role in regulating electrical and contractile activities in the ventricular myocardium. Prior studies indicated angiotensin II (A2) may determine the transmural gradient in Ito, but the effects of A2 on IP and ICaL were unknown. In this study, myocytes were isolated from five muscle layers between epicardium and endocardium. We found a monotonic gradient in both Ip and Ito, with the lowest currents in ENDO. When AT1Rs were inhibited, EPI currents were unaffected, but ENDO currents increased, suggesting endogenous extracellular A2 inhibits both currents in ENDO. IP- and Ito-inhibition by A2 yielded essentially the same K0.5 values, so they may both be regulated by the same mechanism. A2/AT1R-mediated inhibition of IP or Ito or stimulation of ICaL persisted for hours in isolated myocytes, suggesting continuous autocrine secretion of A2 into a restricted diffusion compartment, like the T-system. Detubulation brought EPI IP to its low ENDO value and eliminated A2 sensitivity, so the T-system lumen may indeed be the restricted diffusion compartment. These studies showed that 33–50% of IP, 57–65% of Ito, and a significant fraction of ICaL reside in T-tubule membranes where they are transmurally regulated by autocrine secretion of A2 into the T-system lumen and activation of AT1Rs. Increased AT1R activation regulates each of these currents in a direction expected to increase contractility. Endogenous A2 activation of AT1Rs increases monotonically from EPI to ENDO in a manner similar to reported increases in passive tension when the ventricular chamber fills with blood. We therefore hypothesize load is the signal that regulates A2-activation of AT1Rs, which create a contractile gradient that matches the gradient in load. PMID:24896115

Internet Protocol-Hybrid Opto-Electronic Ring Network (IP-HORNET): A Novel Internet Protocol-Over-Wavelength Division Multiplexing (IP-Over-WDM) Multiple-Access Metropolitan Area Network (MAN)

DTIC Science & Technology

2003-04-01

usage times. End users may range from today’s typical users, such as home and business users, to futuristic users such as automobiles , appliances, hand...has the ability to drop a reprogrammable quantity of wavelengths into the node. The second technological requirement is a protocol that automatically...goal of the R-OADM is to have the ability to drop a reprogrammable number of wavelengths. If it is determined that at peak usage the node must receive M

Hubble Space Telescope Ultraviolet Light Curves Reveal Interesting Properties of CC Sculptoris and RZ Leonis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szkody, Paula; Mukadam, Anjum S.; Toloza, Odette

2017-03-01

Time-tag ultraviolet data obtained on the Hubble Space Telescope in 2013 reveal interesting variability related to the white dwarf spin in the two cataclysmic variables RZ Leo and CC Scl. RZ Leo shows a period at 220 s and its harmonic at 110 s, thus identifying it as a likely Intermediate Polar (IP). The spin signal is not visible in a short single night of ground-based data in 2016, but the shorter exposures in that data set indicate a possible partial eclipse. The much larger UV amplitude of the spin signal in the known IP CC Scl allows the spinmore » of 389 s, previously only seen at outburst, to be visible at quiescence. Spectra created from the peaks and troughs of the spin times indicate a hotter temperature of several thousand degrees during the peak phases, with multiple components contributing to the UV light.« less

Watching Electrons Transfer from Metals to Insulators using Two Photon Photoemission

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johns, James E.

2010-05-01

Ultrafast angle-resolved two photon photoemission was used to study the dynamics and interfacial band structure of ultrathin films adsorbed onto Ag(111). Studies focused on the image potential state (IPS) in each system as a probe for measuring changes in electronic behavior in differing environments. The energetics and dynamics of the IPS at the toluene/Ag(111) interface are strongly dependent upon coverage. For a single monolayer, the first IPS is bound by 0.81 eV below the vacuum level and has a lifetime of 50 femtoseconds (fs). Further adsorption of toluene creates islands of toluene with an exposed wetting layer underneath. The IPSmore » is then split into two peaks, one corresponding to the islands and one corresponding to the monolayer. The wetting layer IPS shows the same dynamics as the monolayer, while the lifetime of the islands increases exponentially with increasing thickness. Furthermore, the island IPS transitions from delocalized to localized within 500 fs, and electrons with larger parallel momenta decay much faster. Attempts were made using a stochastic model to extract the rates of localization and intraband cooling at differing momenta. In sexithiophene (6T) and dihexyl-sexithiophene (DH6T), the IPS was used as a probe to see if the nuclear motion of spectating side chains can interfere with molecular conduction. The energy and band mass of the IPS was measured for 6T and two geometries of DH6T on Ag(111). Electrons injected into the thicker coverages of DH6T grew exponentially heavier until they were completely localized by 230 fs, while those injected into 6T remained nearly free electron like. Based off of lifetime arguments and the density of defects, the most likely cause for the mass enhancement of the IPS in this system is small polaron formation caused by coupling of the electron to vibrations of the alkyl substituents. The energetic relaxation of the molecular adsorbate was also measured to be 20 meV/100 fs for the DH6T, and 0 meV/100 fs for the 6T. This relaxation is consistent with the localization of the charge creating a barrier for it moving from one lattice site to a neighboring one. Finally, the IPS was used to study the evolution of the surface band gap at the Mg/Ag(111) interface. The Mg(0001) surface band gap lies 1.6 eV below the Fermi level, and consequently shows no peak in the projected density of states for the IPS. A method for creating layer by layer growth of Mg on Ag(111) was determined using Auger Spectroscopy and low energy electron diffraction. By monitoring the decay of the intensity of the IPS versus coverage, it was determined that four layers of magnesium on Ag(111) is sufficient to completely eliminate the surface band gap« less

Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP(3)-odors".

PubMed

Chen, S; Lane, A P; Bock, R; Leinders-Zufall, T; Zufall, F

2000-07-01

Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into electrical signals by means of an adenylyl cyclase/cAMP second messenger cascade, but it remains widely debated whether this cAMP cascade mediates transduction for all odorants or only certain odor classes. To address this problem, we have analyzed the generator currents induced by odors that failed to produce cAMP in previous biochemical assays but instead produced IP(3) ("IP(3)-odors"). We show that in single salamander ORNs, sensory responses to "cAMP-odors" and IP(3)-odors are not mutually exclusive but coexist in the same cells. The currents induced by IP(3)-odors exhibit identical biophysical properties as those induced by cAMP odors or direct activation of the cAMP cascade. By disrupting adenylyl cyclase to block cAMP formation using two potent antagonists of adenylyl cyclase, SQ22536 and MDL12330A, we show that this molecular step is necessary for the transduction of both odor classes. To assess whether these results are also applicable to mammals, we examine the electrophysiological responses to IP(3)-odors in intact mouse main olfactory epithelium (MOE) by recording field potentials. The results show that inhibition of adenylyl cyclase prevents EOG responses to both odor classes in mouse MOE, even when "hot spots" with heightened sensitivity to IP(3)-odors are examined.

The Trans Pacific Partnership Agreement and access to HIV treatment in Vietnam.

PubMed

Moir, Hazel V J; Tenni, Brigitte; Gleeson, Deborah; Lopert, Ruth

2018-04-01

In the Trans Pacific Partnership (TPP) Agreement negotiations, the USA successfully pursued intellectual property (IP) provisions that will affect the affordability of medicines, including anti-retrovirals (ARV) for HIV. Vietnam has the lowest GDP per capita of the 12 TPP countries and in 2013 provided ARVs for only 68% of eligible people living with HIV. Using the current Vietnamese IP regime as our base case, we analysed the potential impact of a regime making full use of legal IP flexibilities, and one based on the IP provisions of the final, agreed TPP text. Results indicate that at current funding levels 82% of Vietnam's eligible people living with HIV would receive ARVs if legal flexibilities were fully utilised, while as few as 30% may have access to ARVs under the TPP Agreement - more than halving the proportion currently treated.

Inference of hierarchical regulatory network of estrogen-dependent breast cancer through ChIP-based data

PubMed Central

2010-01-01

Background Global profiling of in vivo protein-DNA interactions using ChIP-based technologies has evolved rapidly in recent years. Although many genome-wide studies have identified thousands of ERα binding sites and have revealed the associated transcription factor (TF) partners, such as AP1, FOXA1 and CEBP, little is known about ERα associated hierarchical transcriptional regulatory networks. Results In this study, we applied computational approaches to analyze three public available ChIP-based datasets: ChIP-seq, ChIP-PET and ChIP-chip, and to investigate the hierarchical regulatory network for ERα and ERα partner TFs regulation in estrogen-dependent breast cancer MCF7 cells. 16 common TFs and two common new TF partners (RORA and PITX2) were found among ChIP-seq, ChIP-chip and ChIP-PET datasets. The regulatory networks were constructed by scanning the ChIP-peak region with TF specific position weight matrix (PWM). A permutation test was performed to test the reliability of each connection of the network. We then used DREM software to perform gene ontology function analysis on the common genes. We found that FOS, PITX2, RORA and FOXA1 were involved in the up-regulated genes. We also conducted the ERα and Pol-II ChIP-seq experiments in tamoxifen resistance MCF7 cells (denoted as MCF7-T in this study) and compared the difference between MCF7 and MCF7-T cells. The result showed very little overlap between these two cells in terms of targeted genes (21.2% of common genes) and targeted TFs (25% of common TFs). The significant dissimilarity may indicate totally different transcriptional regulatory mechanisms between these two cancer cells. Conclusions Our study uncovers new estrogen-mediated regulatory networks by mining three ChIP-based data in MCF7 cells and ChIP-seq data in MCF7-T cells. We compared the different ChIP-based technologies as well as different breast cancer cells. Our computational analytical approach may guide biologists to further study the underlying mechanisms in breast cancer cells or other human diseases. PMID:21167036

ChIP-seq.

PubMed

Kim, Tae Hoon; Dekker, Job

2018-05-01

Owing to its digital nature, ChIP-seq has become the standard method for genome-wide ChIP analysis. Using next-generation sequencing platforms (notably the Illumina Genome Analyzer), millions of short sequence reads can be obtained. The densities of recovered ChIP sequence reads along the genome are used to determine the binding sites of the protein. Although a relatively small amount of ChIP DNA is required for ChIP-seq, the current sequencing platforms still require amplification of the ChIP DNA by ligation-mediated PCR (LM-PCR). This protocol, which involves linker ligation followed by size selection, is the standard ChIP-seq protocol using an Illumina Genome Analyzer. The size-selected ChIP DNA is amplified by LM-PCR and size-selected for the second time. The purified ChIP DNA is then loaded into the Genome Analyzer. The ChIP DNA can also be processed in parallel for ChIP-chip results. © 2018 Cold Spring Harbor Laboratory Press.

Asymmetric quantum-well structures for AlGaN/GaN/AlGaN resonant tunneling diodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Lin'an, E-mail: layang@xidian.edu.cn; Li, Yue; Wang, Ying

Asymmetric quantum-well (QW) structures including the asymmetric potential-barrier and the asymmetric potential-well are proposed for AlGaN/GaN/AlGaN resonant tunneling diodes (RTDs). Theoretical investigation gives that an appropriate decrease in Al composition and thickness for emitter barrier as well as an appropriate increase of both for collector barrier can evidently improve the negative-differential-resistance characteristic of RTD. Numerical simulation shows that RTD with a 1.5-nm-thick GaN well sandwiched by a 1.3-nm-thick Al{sub 0.15}Ga{sub 0.85}N emitter barrier and a 1.7-nm-thick Al{sub 0.25}Ga{sub 0.75}N collector barrier can yield the I-V characteristic having the peak current (Ip) and the peak-to-valley current ratio (PVCR) of 0.39 A andmore » 3.6, respectively, about double that of RTD with a 1.5-nm-thick Al{sub 0.2}Ga{sub 0.8}N for both barriers. It is also found that an introduction of InGaN sub-QW into the diode can change the tunneling mode and achieve higher transmission coefficient of electron. The simulation demonstrates that RTD with a 2.8-nm-thick In{sub 0.03}Ga{sub 0.97}N sub-well in front of a 2.0-nm-thick GaN main-well can exhibit the I-V characteristic having Ip and PVCR of 0.07 A and 11.6, about 7 times and double the value of RTD without sub-QW, respectively. The purpose of improving the structure of GaN-based QW is to solve apparent contradiction between the device structure and the device manufacturability of new generation RTDs for sub-millimeter and terahertz applications.« less

Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer.

PubMed

Husi, Holger; Skipworth, Richard J E; Cronshaw, Andrew; Stephens, Nathan A; Wackerhage, Henning; Greig, Carolyn; Fearon, Kenneth C H; Ross, James A

2015-06-01

Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers. Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples. We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting. We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

76 FR 64283 - Airworthiness Directives; Rolls-Royce plc (RR) Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... currently requires inspecting the intermediate-pressure (IP) compressor rotor shaft rear balance land for...-Trent 800 IP compressor rotor shafts that have been found cracked. This proposed AD would continue to... identified above could lead to IP compressor rotor shaft failure, uncontained engine failure, and damage to...

77 FR 31176 - Airworthiness Directives; Rolls-Royce plc (RR) Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... currently requires inspecting the intermediate-pressure (IP) compressor rotor shaft rear balance land for... detect cracking on the IP compressor rotor rear balance land. IP compressor rotor rear balance land...), without sub-headings. Request To Delete the Re-Balance Requirement American Airlines requested that in the...

The effects of co-administration of 3,4-methylenedioxymethamphetamine ("ecstasy") or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats.

PubMed

Stanley, N; Salem, A; Irvine, R J

2007-04-25

We have recently demonstrated that co-administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") with the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide at an ambient temperature of 22 degrees C significantly increases striatal 5-HT outflow and 5-HT-mediated behaviors. In the present study, using microdialysis, we examined the effects of co-administration of MDMA or para-methoxyamphetamine (PMA) with moclobemide on striatal 5-HT outflow at the elevated ambient temperatures of 30 degrees C. Samples were collected every 30 min for 4 h and analyzed by high-performance liquid chromatography assay with electrochemical detection (HPLC-ED). 5-HT-mediated effects on body temperature and behavior were also recorded. Rats were treated with either saline or 20 mg/kg (i.p.) moclobemide, followed by 10 mg/kg (i.p.) MDMA, 10 mg/kg (i.p.) PMA or saline 60 min later. Both MDMA and PMA produced significant increases in 5-HT outflow (370% peak and 309% peak, respectively, P<0.05). MDMA and PMA significantly increased body temperature (+2.0 degrees C and +2.1 degrees C, respectively, P<0.01) and drug-related behaviors (P<0.05). When MDMA or PMA was co-administered with moclobemide, additional significant increases were seen in 5-HT outflow (850% peak, P<0.01 and 1450% peak, P<0.001, respectively) and only MDMA showed additional significant increase in body temperature (+5.0 degrees C, P<0.001). No additional increases were seen in behavioral activity. When moclobemide was co-administered with MDMA, sustained increases in body temperature were recorded that were significantly higher than with MDMA alone and such increases were not observed in our previous study at normal room temperature. Our results suggest greater risk of MDMA-induced adverse effects on body temperature regulation, compared with PMA, when used in combination with moclobemide at elevated ambient temperatures.

The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning.

PubMed

Alexander, Jon C; McDermott, Carmel M; Tunur, Tumay; Rands, Vicky; Stelly, Claire; Karhson, Debra; Bowlby, Mark R; An, W Frank; Sweatt, J David; Schrader, Laura A

2009-03-01

Potassium channel interacting proteins (KChIPs) are members of a family of calcium binding proteins that interact with Kv4 potassium (K(+)) channel primary subunits and also act as transcription factors. The Kv4 subunit is a primary K(+) channel pore-forming subunit, which contributes to the somatic and dendritic A-type currents throughout the nervous system. These A-type currents play a key role in the regulation of neuronal excitability and dendritic processing of incoming synaptic information. KChIP3 is also known as calsenilin and as the transcription factor, downstream regulatory element antagonist modulator (DREAM), which regulates a number of genes including prodynorphin. KChIP3 and Kv4 primary channel subunits are highly expressed in hippocampus, an area of the brain important for learning and memory. Through its various functions, KChIP3 may play a role in the regulation of synaptic plasticity and learning and memory. We evaluated the role of KChIP3 in a hippocampus-dependent memory task, contextual fear conditioning. Male KChIP3 knockout (KO) mice showed significantly enhanced memory 24 hours after training as measured by percent freezing. In addition, we found that membrane association and interaction with Kv4.2 of KChIP3 protein was significantly decreased and nuclear KChIP3 expression was increased six hours after the fear conditioning training paradigm with no significant change in KChIP3 mRNA. In addition, prodynorphin mRNA expression was significantly decreased six hours after fear conditioning training in wild-type (WT) but not in KO animals. These data suggest a role for regulation of gene expression by KChIP3/DREAM/calsenilin in consolidation of contextual fear conditioning memories.

Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2.

PubMed

Grubb, Søren; Aistrup, Gary L; Koivumäki, Jussi T; Speerschneider, Tobias; Gottlieb, Lisa A; Mutsaers, Nancy A M; Olesen, Søren-Peter; Calloe, Kirstine; Thomsen, Morten B

2015-08-01

Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L). Anesthetized KChIP2(-/-) mice have normal cardiac contraction despite the lower ICa,L, and we hypothesized that the delayed repolarization could contribute to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ₂ protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby augmenting Ca(2+)-induced Ca(2+) release. Ca(2+) transients in disaggregated KChIP2(-/-) cardiomyocytes are indeed comparable to wild-type transients, corroborating the preserved contractile function and suggesting that the compensatory mechanism lies in the Ca(2+)-induced Ca(2+) release event. We next functionally probed dyad structure, ryanodine receptor Ca(2+) sensitivity, and sarcoplasmic reticulum Ca(2+) load and found that increased temporal synchronicity of the Ca(2+) release in KChIP2(-/-) cardiomyocytes may reflect improved dyad structure aiding the compensatory mechanisms in preserving cardiac contractile force. Thus the bimodal effect of KChIP2 on Ito,f and ICa,L constitutes an important regulatory effect of KChIP2 on cardiac contractility, and we conclude that delayed repolarization and improved dyad structure function together to preserve cardiac contraction in KChIP2(-/-) mice. Copyright © 2015 the American Physiological Society.

Use of First-phase Insulin Secretion in Early Diagnosis of Thyroid Diabetes and Type 2 Diabetes Mellitus

PubMed Central

Meng, Li-Heng; Huang, Yao; Zhou, Jia; Liang, Xing-Huan; Xian, Jing; Li, Li; Qin, Ying-Fen

2017-01-01

Background: A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM. Methods: In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups. Furthermore, 96 patients without hyperthyroidism were recruited as control groups (normal glucose tolerance [NGT], impaired glucose regulation [IGR], and T2DM). The following parameters were evaluated: homeostasis model assessment (HOMA)-IR, HOMA-β, modified β-cell function index (MBCI), peak insulin/fasting insulin (IP/I0), AUCins-OGTT, and AUCins-OGTT/AUCglu-OGTT from the oral glucose tolerance test (OGTT) insulin release test were utilized to assess the second-phase insulin secretion, while the IP/I0, AIR0′~10′, and AUCins-IVGTT from the intravenous glucose tolerance test (IVGTT) insulin release test were used to assess the first-phase insulin secretion. Results: In the OGTT, the HOMA-β values of the TNGT and TDM groups were higher than those of the NGT and T2DM groups (all P < 0.05). In the hyperthyroidism groups, the MBCI of the TDM group was lower than that of the TNGT and TIGR groups (all P < 0.05). Among the control groups, the MBCI values of the IGR and T2DM groups were lower than that of the normal glucose tolerance (NGT) group (all P < 0.05). In the IVGTT, insulin secretion peaked for all groups at 2–4 min, except for the T2DM group, which showed a low plateau and no secretion peak. The IP values of the TNGT, TIGR, and TDM groups were higher than those of the NGT, IGR, and T2DM groups (all P < 0.05). The Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the TDM group were higher than those of the T2DM group but were lower than those of the TNGT, TIGR, NGR, and IGR groups (all P < 0.05). Compared with the other five groups, the Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the T2DM group were significantly decreased (all P < 0.05). The Ip/I0 and AUCins-IVGTT values of the TNGT group were higher than those of the NGT group (all P < 0.05). Conclusions: β-cell function in TDM patients is superior to that in T2DM patients. First-phase insulin secretion could be used as an early diagnostic marker to differentiate TDM and T2DM. PMID:28345543

Parallel factor ChIP provides essential internal control for quantitative differential ChIP-seq.

PubMed

Guertin, Michael J; Cullen, Amy E; Markowetz, Florian; Holding, Andrew N

2018-04-17

A key challenge in quantitative ChIP combined with high-throughput sequencing (ChIP-seq) is the normalization of data in the presence of genome-wide changes in occupancy. Analysis-based normalization methods were developed for transcriptomic data and these are dependent on the underlying assumption that total transcription does not change between conditions. For genome-wide changes in transcription factor (TF) binding, these assumptions do not hold true. The challenges in normalization are confounded by experimental variability during sample preparation, processing and recovery. We present a novel normalization strategy utilizing an internal standard of unchanged peaks for reference. Our method can be readily applied to monitor genome-wide changes by ChIP-seq that are otherwise lost or misrepresented through analytical normalization. We compare our approach to normalization by total read depth and two alternative methods that utilize external experimental controls to study TF binding. We successfully resolve the key challenges in quantitative ChIP-seq analysis and demonstrate its application by monitoring the loss of Estrogen Receptor-alpha (ER) binding upon fulvestrant treatment, ER binding in response to estrodiol, ER mediated change in H4K12 acetylation and profiling ER binding in patient-derived xenographs. This is supported by an adaptable pipeline to normalize and quantify differential TF binding genome-wide and generate metrics for differential binding at individual sites.

Modulation by clamping: Kv4 and KChIP interactions.

PubMed

Wang, Kewei

2008-10-01

The rapidly inactivating (A-type) potassium channels regulate membrane excitability that defines the fundamental mechanism of neuronal functions such as pain signaling. Cytosolic Kv channel-interacting proteins KChIPs that belong to neuronal calcium sensor (NCS) family of calcium binding EF-hand proteins co-assemble with Kv4 (Shal) alpha subunits to form a native complex that encodes major components of neuronal somatodendritic A-type K+ current, I(SA), in neurons and transient outward current, I(TO), in cardiac myocytes. The specific binding of auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating properties, surface expression and subunit assembly of Kv4 channels. Here, I attempt to emphasize the interaction between KChIPs and Kv4 based on recent progress made in understanding the structure complex in which a single KChIP1 molecule laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials of designing compounds aimed at disrupting the protein-protein interaction for treatment of membrane excitability-related disorders.

Cardiac-restricted Overexpression of TRAF3 Interacting Protein 2 (TRAF3IP2) Results in Spontaneous Development of Myocardial Hypertrophy, Fibrosis, and Dysfunction *

PubMed Central

Sakamuri, Siva S. V. P.; Siddesha, Jalahalli M.; Saifudeen, Zubaida; Ma, Lixin; Siebenlist, Ulrich; Gardner, Jason D.; Chandrasekar, Bysani

2016-01-01

TRAF3IP2 (TRAF3 interacting protein 2; previously known as CIKS or Act1) is a key intermediate in the normal inflammatory response and the pathogenesis of various autoimmune and inflammatory diseases. Induction of TRAF3IP2 activates IκB kinase (IKK)/NF-κB, JNK/AP-1, and c/EBPβ and stimulates the expression of various inflammatory mediators with negative myocardial inotropic effects. To investigate the role of TRAF3IP2 in heart disease, we generated a transgenic mouse model with cardiomyocyte-specific TRAF3IP2 overexpression (TRAF3IP2-Tg). Echocardiography, magnetic resonance imaging, and pressure-volume conductance catheterization revealed impaired cardiac function in 2-month-old male transgenic (Tg) mice as evidenced by decreased ejection fraction, stroke volume, cardiac output, and peak ejection rate. Moreover, the male Tg mice spontaneously developed myocardial hypertrophy (increased heart/body weight ratio, cardiomyocyte cross-sectional area, GATA4 induction, and fetal gene re-expression). Furthermore, TRAF3IP2 overexpression resulted in the activation of IKK/NF-κB, JNK/AP-1, c/EBPβ, and p38 MAPK and induction of proinflammatory cytokines, chemokines, and extracellular matrix proteins in the heart. Although myocardial hypertrophy decreased with age, cardiac fibrosis (increased number of myofibroblasts and enhanced expression and deposition of fibrillar collagens) increased progressively. Despite these adverse changes, TRAF3IP2 overexpression did not result in cell death at any time period. Interestingly, despite increased mRNA expression, TRAF3IP2 protein levels and activation of its downstream signaling intermediates remained unchanged in the hearts of female Tg mice. The female Tg mice also failed to develop myocardial hypertrophy. In summary, these results demonstrate that overexpression of TRAF3IP2 in male mice is sufficient to induce myocardial hypertrophy, cardiac fibrosis, and contractile dysfunction. PMID:27466370

Mechanisms underlying activation of transient BK current in rabbit urethral smooth muscle cells and its modulation by IP3-generating agonists

PubMed Central

Kyle, Barry D.; Bradley, Eamonn; Large, Roddy; Sergeant, Gerard P.; McHale, Noel G.; Thornbury, Keith D.

2013-01-01

We used the perforated patch-clamp technique at 37°C to investigate the mechanisms underlying the activation of a transient large-conductance K+ (tBK) current in rabbit urethral smooth muscle cells. The tBK current required an elevation of intracellular Ca2+, resulting from ryanodine receptor (RyR) activation via Ca2+-induced Ca2+ release, triggered by Ca2+ influx through L-type Ca2+ (CaV) channels. Carbachol inhibited tBK current by reducing Ca2+ influx and Ca2+ release and altered the shape of spike complexes recorded under current-clamp conditions. The tBK currents were blocked by iberiotoxin and penitrem A (300 and 100 nM, respectively) and were also inhibited when external Ca2+ was removed or the CaV channel inhibitors nifedipine (10 μM) and Cd2+ (100 μM) were applied. The tBK current was inhibited by caffeine (10 mM), ryanodine (30 μM), and tetracaine (100 μM), suggesting that RyR-mediated Ca2+ release contributed to the activation of the tBK current. When IP3 receptors (IP3Rs) were blocked with 2-aminoethoxydiphenyl borate (2-APB, 100 μM), the amplitude of the tBK current was not reduced. However, when Ca2+ release via IP3Rs was evoked with phenylephrine (1 μM) or carbachol (1 μM), the tBK current was inhibited. The effect of carbachol was abolished when IP3Rs were blocked with 2-APB or by inhibition of muscarinic receptors with the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (1 μM). Under current-clamp conditions, bursts of action potentials could be evoked with depolarizing current injection. Carbachol reduced the number and amplitude of spikes in each burst, and these effects were reduced in the presence of 2-APB. In the presence of ryanodine, the number and amplitude of spikes were also reduced, and carbachol was without further effect. These data suggest that IP3-generating agonists can modulate the electrical activity of rabbit urethral smooth muscle cells and may contribute to the effects of neurotransmitters on urethral tone. PMID:23804200

Understanding the current state of infection preventionists through competency, role, and activity self-assessment.

PubMed

Kalp, Ericka L; Marx, James F; Davis, James

2017-06-01

The Association for Professionals in Infection Control and Epidemiology (APIC) MegaSurvey, administered in 2015, was completed by approximately 4,079 APIC members. The survey sought to gain a better understanding the current state of 4 components of infection prevention practice: demographic characteristics, compensation, organizational structure, and practice and competency. The data for this analysis come from the APIC MegaSurvey Practice and Competency domain. Descriptive statistics and χ 2 analyses were conducted to examine differences in infection preventionist (IP) competency, roles, and activity self-assessments. The majority of IPs self-assessed their competency as Proficient compared with Novice or Expert for each of the 8 IP core competency activities. Forty percent of IPs self-rated their competency as Expert in the Preventing/Controlling the Transmission of Infectious Agents/HAIs component. IPs reported Novice competency in Employee/Occupational Health (29%); Cleaning, Sterilization, Disinfection, and Asepsis (23%); and Education and Research categories (22%). Differences in self-rated competency among IPs by discipline type (public health, nurse, and laboratory) were identified. Differences in self-rated competency were identified for each of the 8 IP core competency activities. IPs report using various resource types to gain competency. Future research is needed to identify opportunities to increase competency levels in the weakest-rated competency activities. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Examining Correlates of Problematic Internet Pornography Use Among University Students

PubMed Central

Harper, Cody; Hodgins, David C.

2016-01-01

Background and aims The phenomenon of Internet pornography (IP) addiction is gainingincreasing attention in the popular media and psychological research. What has not been tested empirically is how frequency and amount ofIP use, along with other individual characteristics, are related tosymptoms of IP addiction. Methods 105 female and 86 male university students (mean age 21) from Calgary,Canada, were administered measures of IP use, psychosocial functioning (anxiety and depression, life and relationship satisfaction), addictivepropensities, and addictive IP use. Results Men reported earlier age of exposure and more frequent current IP use than women. Individuals not in relationships reported more frequent use than those in relationships. Frequency of IP use wasnot generally correlated with psychosocial functioning but was significantly positively correlated with level of IP addiction. Higher level of IP addiction was associated with poorer psychosocial functioning and problematic alcohol, cannabis, gambling and, in particular, video game use. A curvilinear association was found between frequency of IP use and level of addiction such that daily or greater IP use was associated with a sharp rise in addictive IP scores. Discussion The failure to find a strong significant relationship between IP use and general psychosocial functioning suggests that the overall effect of IP use is not necessarily harmful in and of itself. Addictiveuse of IP, which is associated with poorer psychosocial functioning, emerges when people begin to use IP daily. PMID:27156383

Geraniol Induces Antinociceptive Effect in Mice Evaluated in Behavioural and Electrophysiological Models.

PubMed

La Rocca, Viviana; da Fonsêca, Diogo Vilar; Silva-Alves, Kerly Shamyra; Ferreira-da-Silva, Francisco Walber; de Sousa, Damião Pergentino; Santos, Priscila Laise; Quintans-Júnior, Lucindo José; Leal-Cardoso, José Henrique; de Almeida, Reinaldo Nóbrega

2017-01-01

Geraniol (GER) is a monoterpene alcohol with various biochemical and pharmacological properties present in the essential oil of more than 160 species of herbs (especially the Cymbopogon genus). In this study, we evaluated the antinociceptive activity of GER in behavioural and electrophysiological in vitro experimental models of nociception using male Swiss mice. GER (12.5, 25 or 50 mg/kg i.p. and 50 or 200 mg/kg p.o.) reduced the number of writhes induced by acetic acid. The opioid antagonist naloxone (5 mg/kg s.c.) administered in mice subsequently treated with GER (25 mg/kg i.p.) did not reverse such antinociceptive activity, suggesting a non-opioid pathway for the mechanism of action. GER (12.5, 25 and 50 mg/kg i.p.) reduced paw licking time in the second phase of the formalin test. Also, in the glutamate test, GER when administered 50 mg/kg i.p. reduced paw licking time, probably modulating glutamatergic neurotransmission. GER blocked reversibly components of the compound action potential (CAP) recorded in isolated sciatic nerve in a concentration- and drug exposure time-dependent manner: 1 mM to 120 min. for the first component and 0.6 mM to 90 min. for the second component. The IC 50 was calculated for the peak-to-peak amplitude (PPA) at 0.48 ± 0.04 mM. The conduction velocity was also reduced by exposure to GER starting from the concentration of 0.3 mM for both components of the CAP. In conclusion, it is suggested that GER has antinociceptive activity, especially in pain related to inflammation, and in part related to reduced peripheral nerve excitability. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Effective Leadership and Management of an ACS Injury Prevention Program: Current Opinions and Perspectives From Where the Rubber Meets the Road.

PubMed

Wolfe, Elizabeth S; Bryant, Elizabeth A

The American College of Surgeons (ACS) mandates that each verified trauma center must have an injury prevention coordinator (IPC); however, Chapter 18 in the Resources for Optimal Care of the Injured Patient (2014) provides minimal information on how to effectively lead or manage an injury prevention (IP) program. This opinion article addresses 3 fundamental components of an effective IP program: (1) construction of an innovative vision of IP programming using current technology; (2) intentional investment and involvement; and (3) stakeholder leadership, engagement, and sustainability. This article also provides leadership and management methods from other professions both within and outside of the health care field that can be translated into sustainable IP program planning, implementation, and longevity.

Examining Correlates of Problematic Internet Pornography Use Among University Students.

PubMed

Harper, Cody; Hodgins, David C

2016-06-01

Background and aims The phenomenon of Internet pornography (IP) addiction is gainingincreasing attention in the popular media and psychological research.What has not been tested empirically is how frequency and amount ofIP use, along with other individual characteristics, are related tosymptoms of IP addiction. Methods 105 female and 86 male university students (mean age 21) from Calgary,Canada, were administered measures of IP use, psychosocial functioning(anxiety and depression, life and relationship satisfaction), addictivepropensities, and addictive IP use. Results Men reported earlier age of exposure and more frequent currentIP use than women. Individuals not in relationships reported morefrequent use than those in relationships. Frequency of IP use wasnot generally correlated with psychosocial functioning but was significantlypositively correlated with level of IP addiction. Higher level ofIP addiction was associated with poorer psychosocial functioning andproblematic alcohol, cannabis, gambling and, in particular, videogame use. A curvilinear association was found between frequency ofIP use and level of addiction such that daily or greater IP use wasassociated with a sharp rise in addictive IP scores. Discussion The failure to find a strong significant relationship between IPuse and general psychosocial functioning suggests that the overalleffect of IP use is not necessarily harmful in and of itself. Addictiveuse of IP, which is associated with poorer psychosocial functioning,emerges when people begin to use IP daily.

Discovering hotspots in functional genomic data superposed on 3D chromatin configuration reconstructions

PubMed Central

Capurso, Daniel; Bengtsson, Henrik; Segal, Mark R.

2016-01-01

The spatial organization of the genome influences cellular function, notably gene regulation. Recent studies have assessed the three-dimensional (3D) co-localization of functional annotations (e.g. centromeres, long terminal repeats) using 3D genome reconstructions from Hi-C (genome-wide chromosome conformation capture) data; however, corresponding assessments for continuous functional genomic data (e.g. chromatin immunoprecipitation-sequencing (ChIP-seq) peak height) are lacking. Here, we demonstrate that applying bump hunting via the patient rule induction method (PRIM) to ChIP-seq data superposed on a Saccharomyces cerevisiae 3D genome reconstruction can discover ‘functional 3D hotspots’, regions in 3-space for which the mean ChIP-seq peak height is significantly elevated. For the transcription factor Swi6, the top hotspot by P-value contains MSB2 and ERG11 – known Swi6 target genes on different chromosomes. We verify this finding in a number of ways. First, this top hotspot is relatively stable under PRIM across parameter settings. Second, this hotspot is among the top hotspots by mean outcome identified by an alternative algorithm, k-Nearest Neighbor (k-NN) regression. Third, the distance between MSB2 and ERG11 is smaller than expected (by resampling) in two other 3D reconstructions generated via different normalization and reconstruction algorithms. This analytic approach can discover functional 3D hotspots and potentially reveal novel regulatory interactions. PMID:26869583

Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line

PubMed Central

Lizio, Marina; Ishizu, Yuri; Itoh, Masayoshi; Lassmann, Timo; Hasegawa, Akira; Kubosaki, Atsutaka; Severin, Jessica; Kawaji, Hideya; Nakamura, Yukio; Suzuki, Harukazu; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R. R.

2015-01-01

Mammals are composed of hundreds of different cell types with specialized functions. Each of these cellular phenotypes are controlled by different combinations of transcription factors. Using a human non islet cell insulinoma cell line (TC-YIK) which expresses insulin and the majority of known pancreatic beta cell specific genes as an example, we describe a general approach to identify key cell-type-specific transcription factors (TFs) and their direct and indirect targets. By ranking all human TFs by their level of enriched expression in TC-YIK relative to a broad collection of samples (FANTOM5), we confirmed known key regulators of pancreatic function and development. Systematic siRNA mediated perturbation of these TFs followed by qRT-PCR revealed their interconnections with NEUROD1 at the top of the regulation hierarchy and its depletion drastically reducing insulin levels. For 15 of the TF knock-downs (KD), we then used Cap Analysis of Gene Expression (CAGE) to identify thousands of their targets genome-wide (KD-CAGE). The data confirm NEUROD1 as a key positive regulator in the transcriptional regulatory network (TRN), and ISL1, and PROX1 as antagonists. As a complimentary approach we used ChIP-seq on four of these factors to identify NEUROD1, LMX1A, PAX6, and RFX6 binding sites in the human genome. Examining the overlap between genes perturbed in the KD-CAGE experiments and genes with a ChIP-seq peak within 50 kb of their promoter, we identified direct transcriptional targets of these TFs. Integration of KD-CAGE and ChIP-seq data shows that both NEUROD1 and LMX1A work as the main transcriptional activators. In the core TRN (i.e., TF-TF only), NEUROD1 directly transcriptionally activates the pancreatic TFs HSF4, INSM1, MLXIPL, MYT1, NKX6-3, ONECUT2, PAX4, PROX1, RFX6, ST18, DACH1, and SHOX2, while LMX1A directly transcriptionally activates DACH1, SHOX2, PAX6, and PDX1. Analysis of these complementary datasets suggests the need for caution in interpreting ChIP-seq datasets. (1) A large fraction of binding sites are at distal enhancer sites and cannot be directly associated to their targets, without chromatin conformation data. (2) Many peaks may be non-functional: even when there is a peak at a promoter, the expression of the gene may not be affected in the matching perturbation experiment. PMID:26635867

Phase I study of intravenous (IV) docetaxel and intraperitoneal (IP) oxaliplatin in recurrent ovarian and fallopian tube cancer.

PubMed

Taylor, Sarah E; Li, Ruosha; Petschauer, Jennifer S; Donovan, Heidi; O'Neal, Sara; Keeler, Amanda W; Zamboni, William C; Edwards, Robert P; Zorn, Kristin K

2015-09-01

The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian (OV), fallopian tube (FT) or peritoneal (PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL). Patients received docetaxel 75mg/m(2) IV day (d) 1 and oxaliplatin escalating from 50mg/m(2) IP d2 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly. Thirteen patients were included. Median number of cycles was 6 (range 1-10). Ten patients had measureable disease. Best response was partial response (PR-2), stable disease (SD-7), and progressive disease (PD-1). Twenty-one Grades 3-4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75mg/m(2) IV and d2 oxaliplatin 50mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50mg/m(2), total unbound drug exposure (AUC) averaged 8 times larger and Cmax reached concentrations 50-fold greater in IP fluid compared to plasma. Docetaxel 75mg/m(2) IV d1 and oxaliplatin 50mg/m(2) IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration. Copyright © 2015 Elsevier Inc. All rights reserved.

Infection prevention staffing and resources in U.S. acute care hospitals: Results from the APIC MegaSurvey.

PubMed

Pogorzelska-Maziarz, Monika; Gilmartin, Heather; Reese, Sara

2018-06-01

Given the changing nature of infection prevention and control (IPC), appropriate infection preventionist (IP) staffing needs to be established. In this study, we aimed to describe current IP staffing levels and IPC department resources in U.S. acute care hospitals. These data came from the 2015 MegaSurvey conducted by the Association of Professionals in Infection Prevention and Epidemiology. Descriptive statistics and bivariate analyses were conducted to examine differences in respondent, facility, and department characteristics by facility size (average inpatient census ≤100 vs >100). Data from 1623 respondents were included. Most (72%) had single-site responsibilities and dedicated 76%-100% of their job to IPC (68%). The overall median IP staffing was 1.25 IPs per 100 inpatient census (interquartile range = 1.81). Almost half (46%) represented facilities with daily inpatient census ≤100; the average number of IPs in these facilities was 1.1 (standard deviation = 0.7). The reported number of IPs increased steadily with higher patient census. Significant differences were observed in IP staffing, responsibilities, and support to the IPC department between smaller and larger hospitals. This study represents the current snapshot of IP staffing and IPC resources in acute care hospitals. Findings indicate important differences between large and small facilities in staffing and IPC resources. The field of infection prevention would benefit from a comprehensive assessment of IPC department staffing and resource needs. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Development of heart failure is independent of K+ channel-interacting protein 2 expression

PubMed Central

Speerschneider, Tobias; Grubb, Søren; Metoska, Artina; Olesen, Søren-Peter; Calloe, Kirstine; Thomsen, Morten B

2013-01-01

Abnormal ventricular repolarization in ion channelopathies and heart disease is a major cause of ventricular arrhythmias and sudden cardiac death. K+ channel-interacting protein 2 (KChIP2) expression is significantly reduced in human heart failure (HF), contributing to a loss of the transient outward K+ current (Ito). We aim to investigate the possible significance of a changed KChIP2 expression on the development of HF and proarrhythmia. Transverse aortic constrictions (TAC) and sham operations were performed in wild-type (WT) and KChIP2−/− mice. Echocardiography was performed before and every 2 weeks after the operation. Ten weeks post-surgery, surface ECG was recorded and we paced the heart in vivo to induce arrhythmias. Afterwards, tissue from the left ventricle was used for immunoblotting. Time courses of HF development were comparable in TAC-operated WT and KChIP2−/− mice. Ventricular protein expression of KChIP2 was reduced by 70% after 10 weeks TAC in WT mice. The amplitudes of the J and T waves were enlarged in KChIP2−/− control mice. Ventricular effective refractory period, RR, QRS and QT intervals were longer in mice with HF compared to sham-operated mice of either genotype. Pacing-induced ventricular tachycardia (VT) was observed in 5/10 sham-operated WT mice compared with 2/10 HF WT mice with HF. Interestingly, and contrary to previously published data, sham-operated KChIP2−/− mice were resistant to pacing-induced VT resulting in only 1/10 inducible mice. KChIP2−/− with HF mice had similar low vulnerability to inducible VT (1/9). Our results suggest that although KChIP2 is downregulated in HF, it is not orchestrating the development of HF. Moreover, KChIP2 affects ventricular repolarization and lowers arrhythmia susceptibility. Hence, downregulation of KChIP2 expression in HF may be antiarrhythmic in mice via reduction of the fast transient outward K+ current. PMID:24099801

Effectiveness of Individual Placement and Support Supported Employment for Young Adults

PubMed Central

Bond, Gary R.; Drake, Robert E.; Campbell, Kikuko

2015-01-01

Objective The Individual Placement and Support (IPS) model of supported employment was first developed in community mental health centers for adults with severe mental illness. While IPS is an established evidence-based practice in this broad population, evidence on its effectiveness focused specifically on young adults has been limited. The current study aimed to address this gap. Methods To investigate the effects of IPS on young adults, the authors conducted a secondary analysis on a pooled sample of 109 unemployed young adults (under age 30) from four randomized controlled trials employing a common research protocol that included a standardized measurement battery and rigorous fidelity monitoring. Researchers assessed these participants over 18 months on nine competitive employment outcome measures. Results On all measures the IPS group had significantly better employment outcomes. Overall, 40 (82%) of IPS participants obtained employment during follow-up compared to 25 (42%) of control participants, Χ2 =17.9, p < .001. IPS participants averaged 25.0 weeks of employment, compared to 7.0 weeks for control participants, t = 4.50, p < .001. Conclusions The current analysis supports a small number of previous studies in showing that IPS is highly effective in helping young adults to attain competitive employment. When young adults acquire competitive jobs and initiate a path toward normal adult roles, they may avoid the cycle of disability and psychiatric patient roles that are demeaning and demoralizing. PMID:25138195

Evaluation of gamma interferon (IFN-gamma)-induced protein 10 (IP-10) responses for detection of cattle infected with Mycobacterium bovis: comparisons to IFN-gamma responses

USDA-ARS?s Scientific Manuscript database

Gamma interferon (IFN-gamma)-induced protein 10 (IP-10) has recently shown promise as a diagnostic biomarker of Mycobacterium tuberculosis infection of humans. The aim of the current study was to compare IP-10 and IFN-gamma responses upon Mycobacterium bovis infection in cattle using archived sample...

The Legalization of Higher Education

ERIC Educational Resources Information Center

Badke, Lara K.

2017-01-01

A complete discussion of intellectual property (IP), faculty rights, and the public good requires a thorough framing of higher education's legal context, from which the rise of legalistic criteria (or legalization) and current IP regime have grown.

Communication and respect for people with dementia: student learning (CARDS) - the development and evaluation of a pilot of an education intervention for pre-qualifying healthcare students.

PubMed

Wood, Julia Helen; Alushi, Ledia; Hammond, John A

2016-04-01

Dementia is an international health priority and healthcare students need to be prepared to work with people living with dementia. There is a paucity of the literature describing appropriate educational interventions for pre-qualifying healthcare students and even fewer that are evaluated. Based on available evidence, an education program was developed aiming to increase students' knowledge and confidence in working with people with dementia (PWD). An introductory program (IP) of classroom sessions and workshops was followed by a volunteer care home experience (CHE) (4 × 3 h). Piloted with physiotherapy (IP n = 55; CHE n = 6) and nursing students (IP n = 20; CHE n = 7), using a survey design, knowledge, and perceived confidence for working with PWD were measured at four time points; baseline, after the IP, after the CHE, and six months later. The data were analyzed using paired t-tests or non-parametric equivalents. Knowledge scores increased after the IP (Time 1-2, p < 0.001, n = 48) and increases were retained after six months (Time 1-4, p < 0.001, n = 40). Perceived confidence increased at six months follow up (Time 1-4, p < 0.001, n = 40) with peaks after the IP (Time 1-2, p < 0.001, n = 47) and CHE (Time 2-3, p = 0.004, n = 13). Physiotherapy and nursing students did not differ on knowledge, but nursing students were more confident at baseline and after the IP. Prior experience equated with greater confidence but no more knowledge. Findings indicate that students' knowledge and confidence to work with PWD improves after this educational intervention, with confidence improving more when supplemented by experience.

A real-time recursive filter for the attitude determination of the Spacelab instrument pointing subsystem

NASA Technical Reports Server (NTRS)

West, M. E.

1992-01-01

A real-time estimation filter which reduces sensitivity to system variations and reduces the amount of preflight computation is developed for the instrument pointing subsystem (IPS). The IPS is a three-axis stabilized platform developed to point various astronomical observation instruments aboard the shuttle. Currently, the IPS utilizes a linearized Kalman filter (LKF), with premission defined gains, to compensate for system drifts and accumulated attitude errors. Since the a priori gains are generated for an expected system, variations result in a suboptimal estimation process. This report compares the performance of three real-time estimation filters with the current LKF implementation. An extended Kalman filter and a second-order Kalman filter are developed to account for the system nonlinearities, while a linear Kalman filter implementation assumes that the nonlinearities are negligible. The performance of each of the four estimation filters are compared with respect to accuracy, stability, settling time, robustness, and computational requirements. It is shown, that for the current IPS pointing requirements, the linear Kalman filter provides improved robustness over the LKF with less computational requirements than the two real-time nonlinear estimation filters.

Dependence of SOL widths on plasma current and density in NSTX H-mode plasmas

NASA Astrophysics Data System (ADS)

Ahn, J.-W.; Maingi, R.; Boedo, J. A.; Soukhanovskii, V.; NSTX Team

2009-06-01

The dependence of various SOL widths on the line-averaged density ( n) and plasma current ( Ip) for the quiescent H-mode plasmas with Type-V ELMs in the National Spherical Torus Experiment (NSTX) was investigated. It is found that the heat flux SOL width ( λq), measured by the IR camera, is virtually insensitive to n and has a strong negative dependence on Ip. This insensitivity of λq to n¯e is consistent with the scaling law from JET H-mode plasmas that shows a very weak dependence on the upstream density. The electron temperature, ion saturation current density, electron density, and electron pressure decay lengths ( λTe, λjsat, λne, and λpe, respectively) measured by the probe showed that λTe and λjsat have strong negative dependence on Ip, whereas λne and λpe revealed only a little or no dependence. The dependence of λTe on Ip is consistent with the scaling law in the literature, while λne and λpe dependence shows a different trend.

47 CFR 73.51 - Determining operating power.

Code of Federal Regulations, 2011 CFR

2011-10-01

... stage of the transmitter, using the following formula: Where: Antenna input power = Ep × Ip × F Ep=DC input voltage of final radio stage. Ip=Total DC input current of final radio stage. F= Efficiency factor...

Arpeggio: harmonic compression of ChIP-seq data reveals protein-chromatin interaction signatures

PubMed Central

Stanton, Kelly Patrick; Parisi, Fabio; Strino, Francesco; Rabin, Neta; Asp, Patrik; Kluger, Yuval

2013-01-01

Researchers generating new genome-wide data in an exploratory sequencing study can gain biological insights by comparing their data with well-annotated data sets possessing similar genomic patterns. Data compression techniques are needed for efficient comparisons of a new genomic experiment with large repositories of publicly available profiles. Furthermore, data representations that allow comparisons of genomic signals from different platforms and across species enhance our ability to leverage these large repositories. Here, we present a signal processing approach that characterizes protein–chromatin interaction patterns at length scales of several kilobases. This allows us to efficiently compare numerous chromatin-immunoprecipitation sequencing (ChIP-seq) data sets consisting of many types of DNA-binding proteins collected from a variety of cells, conditions and organisms. Importantly, these interaction patterns broadly reflect the biological properties of the binding events. To generate these profiles, termed Arpeggio profiles, we applied harmonic deconvolution techniques to the autocorrelation profiles of the ChIP-seq signals. We used 806 publicly available ChIP-seq experiments and showed that Arpeggio profiles with similar spectral densities shared biological properties. Arpeggio profiles of ChIP-seq data sets revealed characteristics that are not easily detected by standard peak finders. They also allowed us to relate sequencing data sets from different genomes, experimental platforms and protocols. Arpeggio is freely available at http://sourceforge.net/p/arpeggio/wiki/Home/. PMID:23873955

Arpeggio: harmonic compression of ChIP-seq data reveals protein-chromatin interaction signatures.

PubMed

Stanton, Kelly Patrick; Parisi, Fabio; Strino, Francesco; Rabin, Neta; Asp, Patrik; Kluger, Yuval

2013-09-01

Researchers generating new genome-wide data in an exploratory sequencing study can gain biological insights by comparing their data with well-annotated data sets possessing similar genomic patterns. Data compression techniques are needed for efficient comparisons of a new genomic experiment with large repositories of publicly available profiles. Furthermore, data representations that allow comparisons of genomic signals from different platforms and across species enhance our ability to leverage these large repositories. Here, we present a signal processing approach that characterizes protein-chromatin interaction patterns at length scales of several kilobases. This allows us to efficiently compare numerous chromatin-immunoprecipitation sequencing (ChIP-seq) data sets consisting of many types of DNA-binding proteins collected from a variety of cells, conditions and organisms. Importantly, these interaction patterns broadly reflect the biological properties of the binding events. To generate these profiles, termed Arpeggio profiles, we applied harmonic deconvolution techniques to the autocorrelation profiles of the ChIP-seq signals. We used 806 publicly available ChIP-seq experiments and showed that Arpeggio profiles with similar spectral densities shared biological properties. Arpeggio profiles of ChIP-seq data sets revealed characteristics that are not easily detected by standard peak finders. They also allowed us to relate sequencing data sets from different genomes, experimental platforms and protocols. Arpeggio is freely available at http://sourceforge.net/p/arpeggio/wiki/Home/.

Low-level biological dosimetry of heterocyclic amine carcinogens isolated from cooked food.

PubMed Central

Turteltaub, K W; Vogel, J S; Frantz, C; Buonarati, M H; Felton, J S

1993-01-01

The bioavailability and the bioreactivity of the carcinogenic heterocyclic amine [2-14C]2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) have been investigated at a dose approximating that likely from the human diet by accelerator mass spectrometry (AMS). [2-14C]PhIP was administered to mice at a dose equivalent ot the consumption of two 100 g beef patties (41 ng/kg). The biological half-life of PhIP was 1 hr, with 90% of the dose being excreted via the urine. Peak tissue PhIP concentrations were reached within 3 hr, with the highest levels in the tissues of the gastrointestinal tract, followed by the liver, kidney, pancreas, and thymus. Since the detection limit by AMS is dependent on the natural abundance of 14C, we have achieved further increases in sensitivity by producing mice that have 20% of the natural abundance of 14C. Use of these 14C-depleted animals allows measurements to be made near the natural level of exposure for many environmental carcinogens. PhIP-DNA adduct levels have also been measured by 32P-postlabeling at doses of 1.0, 10, and 20 mg/kg. The highest adduct levels were found in the pancreas, thymus, heart, and liver and increased linearly with dose. The principal adducts are derived from guanine. Images FIGURE 4. A FIGURE 4. B PMID:8319619

Perioperative haemostatic management of haemophilic mice using normal mouse plasma.

PubMed

Tatsumi, K; Ohashi, K; Kanegae, K; Shim, I K; Okano, T

2013-11-01

Intense haemostatic interventions are required to avoid bleeding complications when surgical procedures are performed on haemophilia patients. The objective of this study was to establish an appropriate protocol for perioperative haemostatic management of haemophilic mice. We assessed the prophylactic haemostatic effects of normal mouse plasma (NMP) on haemophilia B (HB) mice for both a skin flap procedure and a laparotomy. When 500 μL of NMP was administered to the mice, plasma factor IX (FIX:C) levels peaked at 15.1% immediately after intravenous (IV) administration, at 6.1% 2 h after intraperitoneal (IP) administration and at 2.7% 6 h after subcutaneous administration. Administering 500 μL of NMP via IP or IV 30 min in advance enabled the skin flap procedure to be performed safely without any complications. After the laparotomy procedure, several mice in the IP administration group exhibited lethal bleeding, but all mice survived in the IV administration group. Anti-mouse FIX inhibitors did not develop, even after repetitive administrations of NMP. However, human FIX concentrates, especially plasma-derived concentrates, elicited the anti-human FIX inhibitors. The results show that administering 500 μL of NMP via IV or IP 30 min in advance enables surgical procedures to be safely performed on HB mice, and that IV administration is more desirable than IP if the procedure requires opening of the abdominal wall. © 2013 John Wiley & Sons Ltd.

Discovering hotspots in functional genomic data superposed on 3D chromatin configuration reconstructions.

PubMed

Capurso, Daniel; Bengtsson, Henrik; Segal, Mark R

2016-03-18

The spatial organization of the genome influences cellular function, notably gene regulation. Recent studies have assessed the three-dimensional (3D) co-localization of functional annotations (e.g. centromeres, long terminal repeats) using 3D genome reconstructions from Hi-C (genome-wide chromosome conformation capture) data; however, corresponding assessments for continuous functional genomic data (e.g. chromatin immunoprecipitation-sequencing (ChIP-seq) peak height) are lacking. Here, we demonstrate that applying bump hunting via the patient rule induction method (PRIM) to ChIP-seq data superposed on a Saccharomyces cerevisiae 3D genome reconstruction can discover 'functional 3D hotspots', regions in 3-space for which the mean ChIP-seq peak height is significantly elevated. For the transcription factor Swi6, the top hotspot by P-value contains MSB2 and ERG11 - known Swi6 target genes on different chromosomes. We verify this finding in a number of ways. First, this top hotspot is relatively stable under PRIM across parameter settings. Second, this hotspot is among the top hotspots by mean outcome identified by an alternative algorithm, k-Nearest Neighbor (k-NN) regression. Third, the distance between MSB2 and ERG11 is smaller than expected (by resampling) in two other 3D reconstructions generated via different normalization and reconstruction algorithms. This analytic approach can discover functional 3D hotspots and potentially reveal novel regulatory interactions. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Pattern and predictors of sick leave among users of antidepressants: a Danish retrospective register-based cohort study.

PubMed

Gasse, Christiane; Petersen, Liselotte; Chollet, Julien; Saragoussi, Delphine

2013-12-01

Depression is associated with work absenteeism, reduced productivity, and significant personal and societal economic burden. We describe patterns and determinants of sick leave among working Danish antidepressant users. Persons starting antidepressant treatment (January 1, 2004 through December 31, 2005) were identified from a representative 25% sample of the Danish population by linking Danish national registries. Inclusion criteria were age 18-64 years, being in the workforce the week prior to the first antidepressant prescription (index prescription, IP), and no antidepressant prescription in the year prior to the IP. Only sick leaves >2 weeks are centrally registered in Denmark and could be assessed. Cox regression analyses identified predictors of sick leave during the year following the IP, based on previous history of sick leave and clinical and socio-demographic baseline characteristics. In the cohort of 25,908 (59.7% women), sick leave prevalence increased from 37.5% (year prior to IP) to 45.3% (year after the IP); 30.7% were on sick leave for >8 weeks. Incidence peaked (35.5% of individuals) the week after the IP. Of persons with sick leave in the year before the IP, 62.7% were on sick leave the first week after the IP, vs 5.7% of those without previous sick leave. Predictors associated with increased risk of sick leave among those without previous sick leave were unemployment, female gender, age 25-54 years, couples with children, and vocational and higher intermediate education (including e.g. teachers and nurses). Reasons for sick leave, sick leaves of less than 14 days and the indications for antidepressant treatment were unknown. Sick leave was prevalent in persons starting new antidepressant use, often lasting >8 weeks. Previous sick leave was the strongest predictor of subsequent sick leave. © 2013 Elsevier B.V. All rights reserved.

ChIP-PIT: Enhancing the Analysis of ChIP-Seq Data Using Convex-Relaxed Pair-Wise Interaction Tensor Decomposition.

PubMed

Zhu, Lin; Guo, Wei-Li; Deng, Su-Ping; Huang, De-Shuang

2016-01-01

In recent years, thanks to the efforts of individual scientists and research consortiums, a huge amount of chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) experimental data have been accumulated. Instead of investigating them independently, several recent studies have convincingly demonstrated that a wealth of scientific insights can be gained by integrative analysis of these ChIP-seq data. However, when used for the purpose of integrative analysis, a serious drawback of current ChIP-seq technique is that it is still expensive and time-consuming to generate ChIP-seq datasets of high standard. Most researchers are therefore unable to obtain complete ChIP-seq data for several TFs in a wide variety of cell lines, which considerably limits the understanding of transcriptional regulation pattern. In this paper, we propose a novel method called ChIP-PIT to overcome the aforementioned limitation. In ChIP-PIT, ChIP-seq data corresponding to a diverse collection of cell types, TFs and genes are fused together using the three-mode pair-wise interaction tensor (PIT) model, and the prediction of unperformed ChIP-seq experimental results is formulated as a tensor completion problem. Computationally, we propose efficient first-order method based on extensions of coordinate descent method to learn the optimal solution of ChIP-PIT, which makes it particularly suitable for the analysis of massive scale ChIP-seq data. Experimental evaluation the ENCODE data illustrate the usefulness of the proposed model.

Space-Based Telemetry and Range Safety (STARS) Study

NASA Technical Reports Server (NTRS)

Hogie, Keith; Crisuolo, Ed; Parise, Ron

2004-01-01

This presentation will describe the design, development, and testing of a system to collect telemetry, format it into UDP/IP packets, and deliver it to a ground test range using standard IP technologies over a TDRSS link. This presentation will discuss the goal of the STARS IP Formatter along with the overall design. It will also present performance results of the current version of the IP formatter. Finally, it will discuss key issues for supporting constant rate telemetry data delivery when using standard components such as PCI/104 processors, the Linux operating system, Internet Protocols, and synchronous serial interfaces.

Internet over the VDL-2 Subnetwork: the VDL-2/IP Aviation Datalink System

NASA Technical Reports Server (NTRS)

Grappel, R. D.

2000-01-01

This report describes the design to operate the standard Internet communications protocols (IP) over the VHF aviation Data Link Mode 2 (VDL-2) subnetwork. The VDL-2/IP system specified in this report can operate transparently with the current aviation users of VDL-2 (Airline Communications and Reporting System, ACARS and Aeronautical Telecommunications Network, ATN) and proposed users (Flight Information Service via Broadcast, FIS-B). The VDL-2/IP system provides a straightforward mechanisms to utilize inexpensive, commercial off-the-shelf (COTS) communications packages developed for the Internet as part of the aviation datalink system.

Effectiveness of individual placement and support supported employment for young adults.

PubMed

Bond, Gary R; Drake, Robert E; Campbell, Kikuko

2016-08-01

The individual placement and support (IPS) model of supported employment was first developed in community mental health centres for adults with severe mental illness. While IPS is an established evidence-based practice in this broad population, evidence on its effectiveness focused specifically on young adults has been limited. The current study aimed to address this gap. To investigate the effects of IPS on young adults, the authors conducted a secondary analysis on a pooled sample of 109 unemployed young adults (under age 30) from four randomized controlled trials employing a common research protocol that included a standardized measurement battery and rigorous fidelity monitoring. Researchers assessed these participants over 18 months on nine competitive employment outcome measures. On all measures, the IPS group had significantly better employment outcomes. Overall, 40 (82%) of IPS participants obtained employment during follow-up compared with 25 (42%) of control participants, χ(2) = 17.9, P < .001. IPS participants averaged 25.0 weeks of employment, compared with 7.0 weeks for control participants, t = 4.50, P < .001. The current analysis supports a small number of previous studies in showing that IPS is highly effective in helping young adults with severe mental illness to attain competitive employment. When young adults acquire competitive jobs and initiate a path towards normal adult roles, they may avoid the cycle of disability and psychiatric patient roles that are demeaning and demoralizing. © 2014 Wiley Publishing Asia Pty Ltd.

The oxidation/reduction kinetics of the plastoquinone pool controls the appearance of the I-peak in the O-J-I-P chlorophyll fluorescence rise: effects of various electron acceptors.

PubMed

Joly, David; Carpentier, Robert

2007-07-27

Quantitative analysis of the fluorescence induction (FI) rise was used in this study to elucidate the complex effects of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) on thylakoids. Reduced TMPD molecules, responsible for the ADRY agent effect, caused an increase in the amplitude of the O-J rise. Also, only oxidized TMPD molecules were shown to have the ability to bind the Q(B) pocket of photosystem II (PSII). On the other hand, the I-P rise was slowed in proportion with the oxidized TMPD concentration, inducing the clear appearance of the I-peak. While this property was previously thought to be unique to TMPD, this study shows that some artificial electron acceptors of PSII, silicomolybdate, 2,5-dichloro-p-benzoquinone, and phenyl-p-benzoquinone, have a similar effect. These results demonstrated a major role of the oxido-reduction kinetics of the PQ-pool in the resolution of J-I and I-P phases in the FI of isolated thylakoids.

ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia.

PubMed

Landt, Stephen G; Marinov, Georgi K; Kundaje, Anshul; Kheradpour, Pouya; Pauli, Florencia; Batzoglou, Serafim; Bernstein, Bradley E; Bickel, Peter; Brown, James B; Cayting, Philip; Chen, Yiwen; DeSalvo, Gilberto; Epstein, Charles; Fisher-Aylor, Katherine I; Euskirchen, Ghia; Gerstein, Mark; Gertz, Jason; Hartemink, Alexander J; Hoffman, Michael M; Iyer, Vishwanath R; Jung, Youngsook L; Karmakar, Subhradip; Kellis, Manolis; Kharchenko, Peter V; Li, Qunhua; Liu, Tao; Liu, X Shirley; Ma, Lijia; Milosavljevic, Aleksandar; Myers, Richard M; Park, Peter J; Pazin, Michael J; Perry, Marc D; Raha, Debasish; Reddy, Timothy E; Rozowsky, Joel; Shoresh, Noam; Sidow, Arend; Slattery, Matthew; Stamatoyannopoulos, John A; Tolstorukov, Michael Y; White, Kevin P; Xi, Simon; Farnham, Peggy J; Lieb, Jason D; Wold, Barbara J; Snyder, Michael

2012-09-01

Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals.

ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia

PubMed Central

Landt, Stephen G.; Marinov, Georgi K.; Kundaje, Anshul; Kheradpour, Pouya; Pauli, Florencia; Batzoglou, Serafim; Bernstein, Bradley E.; Bickel, Peter; Brown, James B.; Cayting, Philip; Chen, Yiwen; DeSalvo, Gilberto; Epstein, Charles; Fisher-Aylor, Katherine I.; Euskirchen, Ghia; Gerstein, Mark; Gertz, Jason; Hartemink, Alexander J.; Hoffman, Michael M.; Iyer, Vishwanath R.; Jung, Youngsook L.; Karmakar, Subhradip; Kellis, Manolis; Kharchenko, Peter V.; Li, Qunhua; Liu, Tao; Liu, X. Shirley; Ma, Lijia; Milosavljevic, Aleksandar; Myers, Richard M.; Park, Peter J.; Pazin, Michael J.; Perry, Marc D.; Raha, Debasish; Reddy, Timothy E.; Rozowsky, Joel; Shoresh, Noam; Sidow, Arend; Slattery, Matthew; Stamatoyannopoulos, John A.; Tolstorukov, Michael Y.; White, Kevin P.; Xi, Simon; Farnham, Peggy J.; Lieb, Jason D.; Wold, Barbara J.; Snyder, Michael

2012-01-01

Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals. PMID:22955991

MHD and Reconnection Activity During Local Helicity Injection

NASA Astrophysics Data System (ADS)

Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Reusch, J. A.; Richner, N. J.

2016-10-01

Scaling local helicity injection (LHI) to larger devices requires a validated, predictive model of its current drive mechanism. NIMROD simulations predict the injected helical current streams persist in the edge and periodically reconnect to form axisymmetric current rings that travel into the bulk plasma to grow Ip and poloidal flux. In simulation, these events result in discrete bursts of Alfvénic-frequency MHD activity and jumps in Ip of order ΔIp Iinj , in qualitative agreement with large n = 1 activity found in experiment. Fast imaging prior to tokamak formation supports the instability of, and apparent reconnection between, adjacent helical streams. The bursts exhibit toroidal amplitude asymmetries consistent with a kink structure singly line-tied to the injectors. Internal measurements localize this activity to the injector radial location. Pairwise correlations of poloidal Mirnov coil amplitude and phase match expectations of an edge-localized current stream carrying Iinj. Prior to tokamak formation, reconnection from both adjacent helical windings and co-injected current streams are shown to strongly heat impurity ions. After tokamak formation, strong anomalous ion heating in the plasma edge is attributed to continuous reconnection between colinear streams. The n = 1 bursts occur less frequently as Ip rises, likely caused by increased stream stability as Bv rises and qedge drops. This evidence supports the general NIMROD model of LHI, confirms the persistence and role of the edge current streams, and motivates experiments at higher Iinj and BT. Supported by US DOE Grants DE-FG02-96ER54375, DE-SC0006928.

Plasma current start-up using the lower hybrid wave on the TST-2 spherical tokamak

NASA Astrophysics Data System (ADS)

Takase, Y.; Ejiri, A.; Inada, T.; Moeller, C. P.; Shinya, T.; Tsujii, N.; Yajima, S.; Furui, H.; Homma, H.; Imamura, K.; Nakamura, K.; Nakamura, K.; Sonehara, M.; Takeuchi, T.; Togashi, H.; Tsuda, S.; Yoshida, Y.

2015-12-01

Non-inductive plasma current start-up, ramp-up and sustainment by waves in the lower hybrid wave (LHW) frequency range at 200 MHz were investigated on the TST-2 spherical tokamak (R0 ≤ 0.38 m, a ≤ 0.25 m, Bt0 ≤ 0.3T, Ip ≤ 0.14 MA). Experimental results obtained using three types of antenna were compared. Both the highest plasma current (Ip = 18 kA) and the highest current drive figure of merit ηCD≡n¯eIpR0/PRF=1.4 ×1017 A/W/m2 were achieved using the capacitively-coupled combline (CCC) antenna, designed to excite the LHW with a sharp and highly directional wavenumber spectrum. For Ip greater than about 5 kA, high energy electrons accelerated by the LHW become the dominant carrier of plasma current. The low value of ηCD observed so far are believed to be caused by a rapid loss of energetic electrons and parasitic losses of the LHW energy in the plasma periphery. ηCD is expected to improve by an order of magnitude by increasing the plasma current to improve energetic electron confinement. In addition, edge power losses are expected to be reduced by increasing the toroidal magnetic field to improve wave accessibility to the plasma core, and by launching the LHW from the inboard upper region of the torus to achieve better single-pass absorption.

Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats

PubMed Central

XUE, TONG-MIN; TAO, LI-DE; ZHANG, JIE; ZHANG, PEI-JIAN; LIU, XIA; CHEN, GUO-FENG; ZHU, YI-JIA

2016-01-01

The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-κBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-α and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID:26821057

Induced pluripotent stem cells in hematology: current and future applications

PubMed Central

Focosi, D; Amabile, G; Di Ruscio, A; Quaranta, P; Tenen, D G; Pistello, M

2014-01-01

Reprogramming somatic cells into induced pluripotent stem (iPS) cells is nowadays approaching effectiveness and clinical grade. Potential uses of this technology include predictive toxicology, drug screening, pathogenetic studies and transplantation. Here, we review the basis of current iPS cell technology and potential applications in hematology, ranging from disease modeling of congenital and acquired hemopathies to hematopoietic stem and other blood cell transplantation. PMID:24813079

Monitoring nitric oxide (NO) in rat locus coeruleus: differential effects of NO synthase inhibitors.

PubMed

Desvignes, C; Robert, F; Vachette, C; Chouvet, G; Cespuglio, R; Renaud, B; Lambás-Señas, L

1997-04-14

A porphyrinic microsensor combined with in vivo voltammetry was used to monitor extracellular nitric oxide (NO) in the locus coeruleus (LC) of anaesthetized rats. Administration of N omega-nitro-L-arginine p-nitro-anilide (100 mg/kg, i.p) or 7-nitro indazole (30 mg/kg, i.p.), which both inhibit preferentially neuronal NO synthase (NOS), induced a marked decrease in the NO oxidation peak height. On the other hand, N omega-nitro-L-arginine methyl ester (L-NAME) (200 mg/kg, i.p.), a less selective NOS inhibitor, failed to decrease the NO signal. Moreover, intra LC administration of NMDA, known to activate LC noradrenergic neurones, increased the NO signal. This study demonstrates the usefulness of in vivo voltammetry to monitor basal levels of NO and their changes in the LC. Differential effects of NOS inhibitors show that their central activity need to be assessed through in situ measurement of NO before using these inhibitors as neuropharmacological tools.

All-IP-Ethernet architecture for real-time sensor-fusion processing

NASA Astrophysics Data System (ADS)

Hiraki, Kei; Inaba, Mary; Tezuka, Hiroshi; Tomari, Hisanobu; Koizumi, Kenichi; Kondo, Shuya

2016-03-01

Serendipter is a device that distinguishes and selects very rare particles and cells from huge amount of population. We are currently designing and constructing information processing system for a Serendipter. The information processing system for Serendipter is a kind of sensor-fusion system but with much more difficulties: To fulfill these requirements, we adopt All IP based architecture: All IP-Ethernet based data processing system consists of (1) sensor/detector directly output data as IP-Ethernet packet stream, (2) single Ethernet/TCP/IP streams by a L2 100Gbps Ethernet switch, (3) An FPGA board with 100Gbps Ethernet I/F connected to the switch and a Xeon based server. Circuits in the FPGA include 100Gbps Ethernet MAC, buffers and preprocessing, and real-time Deep learning circuits using multi-layer neural networks. Proposed All-IP architecture solves existing problem to construct large-scale sensor-fusion systems.

Functional Cooperation between the IP3 Receptor and Phospholipase C Secures the High Sensitivity to Light of Drosophila Photoreceptors In Vivo

PubMed Central

Kohn, Elkana; Katz, Ben; Yasin, Bushra; Peters, Maximilian; Rhodes, Elisheva; Zaguri, Rachel; Weiss, Shirley

2015-01-01

Drosophila phototransduction is a model system for the ubiquitous phosphoinositide signaling. In complete darkness, spontaneous unitary current events (dark bumps) are produced by spontaneous single Gqα activation, while single-photon responses (quantum bumps) arise from synchronous activation of several Gqα molecules. We have recently shown that most of the spontaneous single Gqα activations do not produce dark bumps, because of a critical phospholipase Cβ (PLCβ) activity level required for bump generation. Surpassing the threshold of channel activation depends on both PLCβ activity and cellular [Ca2+], which participates in light excitation via a still unclear mechanism. We show here that in IP3 receptor (IP3R)-deficient photoreceptors, both light-activated Ca2+ release from internal stores and light sensitivity were strongly attenuated. This was further verified by Ca2+ store depletion, linking Ca2+ release to light excitation. In IP3R-deficient photoreceptors, dark bumps were virtually absent and the quantum-bump rate was reduced, indicating that Ca2+ release from internal stores is necessary to reach the critical level of PLCβ catalytic activity and the cellular [Ca2+] required for excitation. Combination of IP3R knockdown with reduced PLCβ catalytic activity resulted in highly suppressed light responses that were partially rescued by cellular Ca2+ elevation, showing a functional cooperation between IP3R and PLCβ via released Ca2+. These findings suggest that in contrast to the current dogma that Ca2+ release via IP3R does not participate in light excitation, we show that released Ca2+ plays a critical role in light excitation. The positive feedback between PLCβ and IP3R found here may represent a common feature of the inositol-lipid signaling. PMID:25673847

ASPeak: an abundance sensitive peak detection algorithm for RIP-Seq.

PubMed

Kucukural, Alper; Özadam, Hakan; Singh, Guramrit; Moore, Melissa J; Cenik, Can

2013-10-01

Unlike DNA, RNA abundances can vary over several orders of magnitude. Thus, identification of RNA-protein binding sites from high-throughput sequencing data presents unique challenges. Although peak identification in ChIP-Seq data has been extensively explored, there are few bioinformatics tools tailored for peak calling on analogous datasets for RNA-binding proteins. Here we describe ASPeak (abundance sensitive peak detection algorithm), an implementation of an algorithm that we previously applied to detect peaks in exon junction complex RNA immunoprecipitation in tandem experiments. Our peak detection algorithm yields stringent and robust target sets enabling sensitive motif finding and downstream functional analyses. ASPeak is implemented in Perl as a complete pipeline that takes bedGraph files as input. ASPeak implementation is freely available at https://sourceforge.net/projects/as-peak under the GNU General Public License. ASPeak can be run on a personal computer, yet is designed to be easily parallelizable. ASPeak can also run on high performance computing clusters providing efficient speedup. The documentation and user manual can be obtained from http://master.dl.sourceforge.net/project/as-peak/manual.pdf.

Non-solenoidal Plasma Startup in the Pegasus Toroidal Experiment

NASA Astrophysics Data System (ADS)

Sontag, Aaron

2008-11-01

Non-solenoidal (NS) startup will simplify the design of future tokamaks by eliminating need for a central solenoid and is required for an ST based CTF. In Pegasus, washer-stack current sources (plasma guns) are used to initiate NS discharges via point-source DC helicity injection. Current injected parallel to the helical vacuum field can relax into a tokamak-like configuration with toroidally-averaged closed flux and tokamak-like confinement. This requires no modification of the vacuum vessel and is scalable to fusion grade systems with proper geometry. Guns in the divertor region create discharges with Ip up to 50 kA, 3 times the vacuum windup. Nonlinear 3D simulation with NIMROD shows excitation of a line-tied kink, producing poloidal flux amplification. Evidence of flux amplification includes: reversal of edge poloidal magnetic flux; Ip increase over vacuum geometric windup; plasma position subject to radial force balance; and persistence of Ip after gun shut-off. Equilibria show high edge current (li = 0.2) and elevated q (qmin> 6), allowing access to high IN (IN> 12). Guns at the outboard midplane produce Ip up to 7 times the vacuum windup with large n=1 activity when edge q passes through rational surfaces. Line averaged density up to 2x10^19 m-3 after relaxation shows an increase in particle confinement over non-relaxed cases. Maximum Ip is determined by helicity and radial force balance, tokamak stability, and Taylor relaxation. Coupling midplane gun discharges to other CD is straightforward due to Ip decay times >3 ms. Poloidal field induction has been used to create NS discharges up to 80 kA and gun plasmas with Ip of 60 kA have been ramped to over 100 kA by including OH drive. Present research is aimed at understanding the physics of this technique in order to form NS targets in excess of 200 kA and design NS startup systems for larger devices.

Integrated modelling of steady-state scenarios and heating and current drive mixes for ITER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murakami, Masanori; Park, Jin Myung; Giruzzi, G.

2011-01-01

Recent progress on ITER steady-state (SS) scenario modelling by the ITPA-IOS group is reviewed. Code-to-code benchmarks as the IOS group's common activities for the two SS scenarios (weak shear scenario and internal transport barrier scenario) are discussed in terms of transport, kinetic profiles, and heating and current drive (CD) sources using various transport codes. Weak magnetic shear scenarios integrate the plasma core and edge by combining a theory-based transport model (GLF23) with scaled experimental boundary profiles. The edge profiles (at normalized radius rho = 0.8-1.0) are adopted from an edge-localized mode-averaged analysis of a DIII-D ITER demonstration discharge. A fullymore » noninductive SS scenario is achieved with fusion gain Q = 4.3, noninductive fraction f(NI) = 100%, bootstrap current fraction f(BS) = 63% and normalized beta beta(N) = 2.7 at plasma current I(p) = 8MA and toroidal field B(T) = 5.3 T using ITER day-1 heating and CD capability. Substantial uncertainties come from outside the radius of setting the boundary conditions (rho = 0.8). The present simulation assumed that beta(N)(rho) at the top of the pedestal (rho = 0.91) is about 25% above the peeling-ballooning threshold. ITER will have a challenge to achieve the boundary, considering different operating conditions (T(e)/T(i) approximate to 1 and density peaking). Overall, the experimentally scaled edge is an optimistic side of the prediction. A number of SS scenarios with different heating and CD mixes in a wide range of conditions were explored by exploiting the weak-shear steady-state solution procedure with the GLF23 transport model and the scaled experimental edge. The results are also presented in the operation space for DT neutron power versus stationary burn pulse duration with assumed poloidal flux availability at the beginning of stationary burn, indicating that the long pulse operation goal (3000s) at I(p) = 9 MA is possible. Source calculations in these simulations have been revised for electron cyclotron current drive including parallel momentum conservation effects and for neutral beam current drive with finite orbit and magnetic pitch effects.« less

The relationship between hippocampal EEG theta activity and locomotor behaviour in freely moving rats: effects of vigabatrin.

PubMed

Bouwman, B M; van Lier, H; Nitert, H E J; Drinkenburg, W H I M; Coenen, A M L; van Rijn, C M

2005-01-30

The relationship between hippocampal electroencephalogram (EEG) theta activity and locomotor speed in both spontaneous and forced walking conditions was studied in rats after vigabatrin injection (500 mg/kg i.p.). Vigabatrin increased the percentage of time that rats spent being immobile. During spontaneous walking in the open field, the speed of locomotion was increased by vigabatrin, while theta peak frequency was decreased. Vigabatrin also reduced the theta peak frequency during forced (speed controlled) walking. There was only a weak positive correlation (r=0.22) between theta peak frequency and locomotor speed for the saline condition. Furthermore, vigabatrin abolishes the weak relationship between speed of locomotion and theta peak frequency. Vigabatrin and saline did not differ in the slope of the regression line, but showed different offset points at the theta peak frequency axis. Thus, other factors than speed of locomotion seem to be involved in determination of the theta peak frequency.

[Unresolved issues in the evaluation of research projects involving induced pluripotent stem cells (iPS)].

PubMed

Casado, María; de Lecuona, Itziar

2013-01-01

This paper identifies problems and analyzes those conflicts posed by the evaluation of research projects involving the collection and use of human induced pluripotent stem cells (iPS) in Spain. Current legislation is causing problems of interpretation, circular and unnecessary referrals, legal uncertainty and undue delays. Actually, this situation may cause a lack of control and monitoring, and even some paralysis in regenerative medicine and cell therapy research, that is a priority nowadays. The analysis of the current legislation and its bioethical implications, led us to conclude that the review of iPS research projects cannot be assimilated to the evaluation of research projects that involve human embryonic stem cell (hESC). In this context, our proposal is based on the review by the Research Ethics Committees and the checkout by the Spanish Comission of Guarantees for Donation and Use of Human Cells and Tissues (CGDUCTH) of human iPS cells research projects. Moreover, this article claims for a more transparent research system, by effectively articulating the Registry on Research Projects. Finally, a model of verification protocol (checklist) for checking out biomedical research projects involving human iPS cells is suggested.

β Subunits Functionally Differentiate Human Kv4.3 Potassium Channel Splice Variants

PubMed Central

Abbott, Geoffrey W.

2017-01-01

The human ventricular cardiomyocyte transient outward K+ current (Ito) mediates the initial phase of myocyte repolarization and its disruption is implicated in Brugada Syndrome and heart failure (HF). Human cardiac Ito is generated primarily by two Kv4.3 splice variants (Kv4.3L and Kv4.3S, diverging only by a C-terminal, S6-proximal, 19-residue stretch unique to Kv4.3L), which are differentially remodeled in HF, but considered functionally alike at baseline. Kv4.3 is regulated in human heart by β subunits including KChIP2b and KCNEs, but their effects were previously assumed to be Kv4.3 isoform-independent. Here, this assumption was tested experimentally using two-electrode voltage-clamp analysis of human subunits co-expressed in Xenopus laevis oocytes. Unexpectedly, Kv4.3L-KChIP2b channels exhibited up to 8-fold lower current augmentation, 40% slower inactivation, and 5 mV-shifted steady-state inactivation compared to Kv4.3S-KChIP2b. A synthetic peptide mimicking the 19-residue stretch diminished these differences, reinforcing the importance of this segment in mediating Kv4.3 regulation by KChIP2b. KCNE subunits induced further functional divergence, including a 7-fold increase in Kv4.3S-KCNE4-KChIP2b current compared to Kv4.3L-KCNE4-KChIP2b. The discovery of β-subunit-dependent functional divergence in human Kv4.3 splice variants suggests a C-terminal signaling hub is crucial to governing β-subunit effects upon Kv4.3, and demonstrates the potential significance of differential Kv4.3 gene-splicing and β subunit expression in myocyte physiology and pathobiology. PMID:28228734

β Subunits Functionally Differentiate Human Kv4.3 Potassium Channel Splice Variants.

PubMed

Abbott, Geoffrey W

2017-01-01

The human ventricular cardiomyocyte transient outward K + current ( I to ) mediates the initial phase of myocyte repolarization and its disruption is implicated in Brugada Syndrome and heart failure (HF). Human cardiac I to is generated primarily by two Kv4.3 splice variants (Kv4.3L and Kv4.3S, diverging only by a C-terminal, S6-proximal, 19-residue stretch unique to Kv4.3L), which are differentially remodeled in HF, but considered functionally alike at baseline. Kv4.3 is regulated in human heart by β subunits including KChIP2b and KCNEs, but their effects were previously assumed to be Kv4.3 isoform-independent. Here, this assumption was tested experimentally using two-electrode voltage-clamp analysis of human subunits co-expressed in Xenopus laevis oocytes. Unexpectedly, Kv4.3L-KChIP2b channels exhibited up to 8-fold lower current augmentation, 40% slower inactivation, and 5 mV-shifted steady-state inactivation compared to Kv4.3S-KChIP2b. A synthetic peptide mimicking the 19-residue stretch diminished these differences, reinforcing the importance of this segment in mediating Kv4.3 regulation by KChIP2b. KCNE subunits induced further functional divergence, including a 7-fold increase in Kv4.3S-KCNE4-KChIP2b current compared to Kv4.3L-KCNE4-KChIP2b. The discovery of β-subunit-dependent functional divergence in human Kv4.3 splice variants suggests a C-terminal signaling hub is crucial to governing β-subunit effects upon Kv4.3, and demonstrates the potential significance of differential Kv4.3 gene-splicing and β subunit expression in myocyte physiology and pathobiology.

Two different electrical properties can improve transoceanic cable-route mapping

USGS Publications Warehouse

Wynn, J.; McGinnis, T.

2001-01-01

Induced polarization (IP) measurements made in the marine environment were investigated to map and remotely characterize the top 6-10 meters of the seafloor. The continuous resistivity profiling with cone-penetrometer tests, providing important information to engineers planning transoceanic cable routes, was also described. The IP effect and resistivity were identified as the two electric properties to improve transoceanic cable-route mapping. The measurement of IP and resistivity was found to depend on electrical current.

Different KChIPs compete for heteromultimeric assembly with pore-forming Kv4 subunits.

PubMed

Zhou, Jingheng; Tang, Yiquan; Zheng, Qin; Li, Meng; Yuan, Tianyi; Chen, Liangyi; Huang, Zhuo; Wang, KeWei

2015-06-02

Auxiliary Kv channel-interacting proteins 1-4 (KChIPs1-4) coassemble with pore-forming Kv4 α-subunits to form channel complexes underlying somatodendritic subthreshold A-type current that regulates neuronal excitability. It has been hypothesized that different KChIPs can competitively bind to Kv4 α-subunit to form variable channel complexes that can exhibit distinct biophysical properties for modulation of neural function. In this study, we use single-molecule subunit counting by total internal reflection fluorescence microscopy in combinations with electrophysiology and biochemistry to investigate whether different isoforms of auxiliary KChIPs, KChIP4a, and KChIP4bl, can compete for binding of Kv4.3 to coassemble heteromultimeric channel complexes for modulation of channel function. To count the number of photobleaching steps solely from cell membrane, we take advantage of a membrane tethered k-ras-CAAX peptide that anchors cytosolic KChIP4 proteins to the surface for reduction of background noise. Single-molecule subunit counting reveals that the number of KChIP4 isoforms in Kv4.3-KChIP4 complexes can vary depending on the KChIP4 expression level. Increasing the amount of KChIP4bl gradually reduces bleaching steps of KChIP4a isoform proteins, and vice versa. Further analysis of channel gating kinetics from different Kv4-KChIP4 subunit compositions confirms that both KChIP4a and KChIP4bl can modulate the channel complex function upon coassembly. Taken together, our findings show that auxiliary KChIPs can heteroassemble with Kv4 in a competitive manner to form heteromultimeric Kv4-KChIP4 channel complexes that are biophysically distinct and regulated under physiological or pathological conditions. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Modeling human neurological disorders with induced pluripotent stem cells.

PubMed

Imaizumi, Yoichi; Okano, Hideyuki

2014-05-01

Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained knowledge in the form of actual examples. © 2013 International Society for Neurochemistry.

Anomalous Ion Heating, Intrinsic and Induced Rotation in the Pegasus Toroidal Experiment

NASA Astrophysics Data System (ADS)

Burke, M. G.; Barr, J. L.; Bongard, M. W.; Fonck, R. J.; Hinson, E. T.; Perry, J. M.; Redd, A. J.; Thome, K. E.

2014-10-01

Pegasus plasmas are initiated through either standard, MHD stable, inductive current drive or non-solenoidal local helicity injection (LHI) current drive with strong reconnection activity, providing a rich environment to study ion dynamics. During LHI discharges, a large amount of anomalous impurity ion heating has been observed, with Ti ~ 800 eV but Te < 100 eV. The ion heating is hypothesized to be a result of large-scale magnetic reconnection activity, as the amount of heating scales with increasing fluctuation amplitude of the dominant, edge localized, n = 1 MHD mode. Chordal Ti spatial profiles indicate centrally peaked temperatures, suggesting a region of good confinement near the plasma core surrounded by a stochastic region. LHI plasmas are observed to rotate, perhaps due to an inward radial current generated by the stochastization of the plasma edge by the injected current streams. H-mode plasmas are initiated using a combination of high-field side fueling and Ohmic current drive. This regime shows a significant increase in rotation shear compared to L-mode plasmas. In addition, these plasmas have been observed to rotate in the counter-Ip direction without any external momentum sources. The intrinsic rotation direction is consistent with predictions from the saturated Ohmic confinement regime. Work supported by US DOE Grant DE-FG02-96ER54375.

The introduction of new vaccines into developing countries. III. The role of intellectual property.

PubMed

Mahoney, Richard T; Pablos-Mendez, Ariel; Ramachandran, S

2004-01-26

The development of new vaccines that address the particular needs of developing countries has been proceeding slowly. A number of new public sector vaccine research and development initiatives have been launched to address this problem. These new initiatives find that they often wish to collaborate with the private sector and, in collaborating with the private sector, they must address issues of intellectual property (IP) management. It has not been well understood why IP management is important and how such management by public sector groups can best be conducted. IP management has become very important because vaccine research and development is driven by the regulatory process. The regulatory process has increased the cost of vaccine development to very high levels especially for the highly sophisticated new vaccines currently under development. Thus, investors seek IP protection for the required large investments. Conversely, we assert this concept as a new insight, IP rights are essential for mobilizing the significant funds necessary to meet regulatory requirements. Thus, IP rights are of value not only for investors but also for the public at large. In the absence of public sector mechanisms to carry out the functions that the private sector currently conducts, the public sector needs to increase its sophistication in IP management and needs to identify and implement strategies that will help the public sector to achieve its public health goals, especially for the poor and, among these individuals, the poor in developing countries. This paper suggests some strategies that might be used by the public sector to help achieve its public health goals, especially for the poor.

THE 2012 RISE OF THE REMARKABLE TYPE IIn SN 2009ip

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prieto, Jose L.; Brimacombe, J.; Drake, A. J.

2013-02-01

Recent observations by Mauerhan et al. have shown the unprecedented transition of the previously identified luminous blue variable (LBV) and supernova (SN) impostor SN 2009ip to a real Type IIn SN explosion. We present {approx}100 optical R- and I-band photometric measurements of SN 2009ip obtained between UT 2012 September 23.6 and October 9.6, using 0.3-0.4 m aperture telescopes from the Coral Towers Observatory in Cairns, Australia. The light curves show well-defined phases, including very rapid brightening early on (0.5 mag in 6 hr observed during the night of September 24), a transition to a much slower rise between September 25more » and September 28, and a plateau/peak around October 7. These changes are coincident with the reported spectroscopic changes that most likely mark the start of a strong interaction between the fast SN ejecta and a dense circumstellar medium formed during the LBV eruptions observed in recent years. In the 16-day observing period, SN 2009ip brightened by 3.7 mag from I = 17.4 mag on September 23.6 (M{sub I} {approx_equal} -14.2) to I = 13.7 mag (M{sub I} {approx_equal} -17.9) on October 9.6, radiating {approx}3 Multiplication-Sign 10{sup 49} erg in the optical wavelength range. As of 2012 October 9.6, SN 2009ip is more luminous than most Type IIP SN and comparable to other Type IIn SN.« less

Tensions inherent in the evolving role of the infection preventionist.

PubMed

Conway, Laurie J; Raveis, Victoria H; Pogorzelska-Maziarz, Monika; Uchida, May; Stone, Patricia W; Larson, Elaine L

2013-11-01

The role of infection preventionists (IPs) is expanding in response to demands for quality and transparency in health care. Practice analyses and survey research have demonstrated that IPs spend a majority of their time on surveillance and are increasingly responsible for prevention activities and management; however, deeper qualitative aspects of the IP role have rarely been explored. We conducted a qualitative content analysis of in-depth interviews with 19 IPs at hospitals throughout the United States to describe the current IP role, specifically the ways that IPs effect improvements and the facilitators and barriers they face. The narratives document that the IP role is evolving in response to recent changes in the health care landscape and reveal that this progression is associated with friction and uncertainty. Tensions inherent in the evolving role of the IP emerged from the interviews as 4 broad themes: (1) expanding responsibilities outstrip resources, (2) shifting role boundaries create uncertainty, (3) evolving mechanisms of influence involve trade-offs, and (4) the stress of constant change is compounded by chronic recurring challenges. Advances in implementation science, data standardization, and training in leadership skills are needed to support IPs in their evolving role. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Nuclear inositol 1,4,5-trisphosphate is a necessary and conserved signal for the induction of both pathological and physiological cardiomyocyte hypertrophy.

PubMed

Arantes, Lilian A M; Aguiar, Carla J; Amaya, Maria Jimena; Figueiró, Núbia C G; Andrade, Lídia M; Rocha-Resende, Cibele; Resende, Rodrigo R; Franchini, K G; Guatimosim, Silvia; Leite, M Fatima

2012-10-01

It is well established that inositol 1,4,5-trisphosphate (IP3) dependent Ca(2+) signaling plays a crucial role in cardiomyocyte hypertrophy. However, it is not yet known whether nuclear IP3 represents a Ca(2+) mobilizing pathway involved in this process. The goal of the current work was to investigate the specific role of nuclear IP3 in cardiomyocyte hypertrophic response. In this work, we used an adenovirus construct that selectively buffers IP3 in the nuclear region of neonatal cardiomyocytes. We showed for the first time that nuclear IP3 mediates endothelin-1 (ET-1) induced hypertrophy. We also found that both calcineurin (Cn)/nuclear factor of activated T Cells (NFAT) and histone deacetylase-5 (HDAC5) pathways require nuclear IP3 to mediate pathological cardiomyocyte growth. Additionally, we found that nuclear IP3 buffering inhibited insulin-like growth factor-1 (IGF-1) induced hypertrophy and prevented reexpression of fetal gene program. Together, these results demonstrated that nuclear IP3 is an essential and a conserved signal for both pathological and physiological forms of cardiomyocyte hypertrophy. Copyright © 2012. Published by Elsevier Ltd.

Representation of Semantic Similarity in the Left Intraparietal Sulcus: Functional Magnetic Resonance Imaging Evidence

PubMed Central

Neyens, Veerle; Bruffaerts, Rose; Liuzzi, Antonietta G.; Kalfas, Ioannis; Peeters, Ronald; Keuleers, Emmanuel; Vogels, Rufin; De Deyne, Simon; Storms, Gert; Dupont, Patrick; Vandenberghe, Rik

2017-01-01

According to a recent study, semantic similarity between concrete entities correlates with the similarity of activity patterns in left middle IPS during category naming. We examined the replicability of this effect under passive viewing conditions, the potential role of visuoperceptual similarity, where the effect is situated compared to regions that have been previously implicated in visuospatial attention, and how it compares to effects of object identity and location. Forty-six subjects participated. Subjects passively viewed pictures from two categories, musical instruments and vehicles. Semantic similarity between entities was estimated based on a concept-feature matrix obtained in more than 1,000 subjects. Visuoperceptual similarity was modeled based on the HMAX model, the AlexNet deep convolutional learning model, and thirdly, based on subjective visuoperceptual similarity ratings. Among the IPS regions examined, only left middle IPS showed a semantic similarity effect. The effect was significant in hIP1, hIP2, and hIP3. Visuoperceptual similarity did not correlate with similarity of activity patterns in left middle IPS. The semantic similarity effect in left middle IPS was significantly stronger than in the right middle IPS and also stronger than in the left or right posterior IPS. The semantic similarity effect was similar to that seen in the angular gyrus. Object identity effects were much more widespread across nearly all parietal areas examined. Location effects were relatively specific for posterior IPS and area 7 bilaterally. To conclude, the current findings replicate the semantic similarity effect in left middle IPS under passive viewing conditions, and demonstrate its anatomical specificity within a cytoarchitectonic reference frame. We propose that the semantic similarity effect in left middle IPS reflects the transient uploading of semantic representations in working memory. PMID:28824405

KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain.

PubMed

Rhodes, Kenneth J; Carroll, Karen I; Sung, M Amy; Doliveira, Lisa C; Monaghan, Michael M; Burke, Sharon L; Strassle, Brian W; Buchwalder, Lynn; Menegola, Milena; Cao, Jie; An, W Frank; Trimmer, James S

2004-09-08

Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family alpha subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs1-4 and Kv4 family alpha subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP2, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 alpha subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.

Development and Evaluation of a Computerized Engagement Intervention for IPS Supported Employment

ERIC Educational Resources Information Center

Haslett, William R.

2013-01-01

Background: Current information technology offers the promise of innovative approaches to engagement for mental health. Specific psychosocial services may also benefit from technology-based engagement interventions. Individual Placement and Support (IPS) is an evidence-based service that helps people who have a severe mental illness to gain…

An Elevation in Physical Coupling of Type 1 IP3 Receptors to TRPC3 Channels Constricts Mesenteric Arteries in Genetic Hypertension

PubMed Central

Adebiyi, Adebowale; Thomas-Gatewood, Candice M.; Leo, M. Dennis; Kidd, Michael W.; Neeb, Zachary P.; Jaggar, Jonathan H.

2013-01-01

Hypertension is associated with an elevation in agonist-induced vasoconstriction, but mechanisms involved require further investigation. Many vasoconstrictors bind to phospholipase C-coupled receptors, leading to an elevation in inositol 1,4,5-trisphosphate (IP3) that activates sarcoplasmic reticulum (SR) IP3 receptors (IP3Rs). In cerebral artery myocytes, IP3Rs release SR Ca2+ and can physically couple to canonical transient receptor potential 3 (TRPC3) channels in a caveolin-1-containing macromolecular complex, leading to cation current (ICat) activation that stimulates vasoconstriction. Here, we investigated mechanisms by which IP3Rs control vascular contractility in systemic arteries and IP3R involvement in elevated agonist-induced vasoconstriction during hypertension. Total and plasma membrane-localized TRPC3 protein was ~2.7- and 2-fold higher in mesenteric arteries of hypertensive spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rat controls, respectively. In contrast, IP3R1, TRPC1, TRPC6, and caveolin-1 expression was similar. TRPC3 expression was also similar in arteries of pre-hypertensive SHR and WKY rats. Control, IP3- and endothelin-1 (ET-1)-induced FRET between IP3R1 and TRPC3 was higher in hypertensive SHR than WKY myocytes. IP3-induced ICat was ~3-fold larger in SHR myocytes. Pyr3, a selective TRPC3 channel blocker, and CIRBP-TAT, an IP3R-TRP physical coupling inhibitor, reduced IP3-induced ICat and ET-1-induced vasoconstriction more in SHR than WKY myocytes and arteries. Thapsigargin, a SR Ca2+-ATPase blocker, did not alter ET-1-stimulated vasoconstriction in SHR or WKY arteries. These data indicate that ET-1 stimulates physical coupling of IP3R1 to TRPC3 channels in mesenteric artery myocytes, leading to vasoconstriction. Furthermore, an elevation in IP3R1 to TRPC3 channel molecular coupling augments ET-1-induced vasoconstriction during hypertension. PMID:23045459

Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons.

PubMed

Amarillo, Yimy; De Santiago-Castillo, Jose A; Dougherty, Kevin; Maffie, Jonathon; Kwon, Elaine; Covarrubias, Manuel; Rudy, Bernardo

2008-04-15

Kv4 channels mediate most of the somatodendritic subthreshold operating A-type current (I(SA)) in neurons. This current plays essential roles in the regulation of spike timing, repetitive firing, dendritic integration and plasticity. Neuronal Kv4 channels are thought to be ternary complexes of Kv4 pore-forming subunits and two types of accessory proteins, Kv channel interacting proteins (KChIPs) and the dipeptidyl-peptidase-like proteins (DPPLs) DPPX (DPP6) and DPP10. In heterologous cells, ternary Kv4 channels exhibit inactivation that slows down with increasing depolarization. Here, we compared the voltage dependence of the inactivation rate of channels expressed in heterologous mammalian cells by Kv4.2 proteins with that of channels containing Kv4.2 and KChIP1, Kv4.2 and DPPX-S, or Kv4.2, KChIP1 and DPPX-S, and found that the relation between inactivation rate and membrane potential is distinct for these four conditions. Moreover, recordings from native neurons showed that the inactivation kinetics of the I(SA) in cerebellar granule neurons has voltage dependence that is remarkably similar to that of ternary Kv4 channels containing KChIP1 and DPPX-S proteins in heterologous cells. The fact that this complex and unique behaviour (among A-type K(+) currents) is observed in both the native current and the current expressed in heterologous cells by the ternary complex containing Kv4, DPPX and KChIP proteins supports the hypothesis that somatically recorded native Kv4 channels in neurons include both types of accessory protein. Furthermore, quantitative global kinetic modelling showed that preferential closed-state inactivation and a weakly voltage-dependent opening step can explain the slowing of the inactivation rate with increasing depolarization. Therefore, it is likely that preferential closed-state inactivation is the physiological mechanism that regulates the activity of both ternary Kv4 channel complexes and native I(SA)-mediating channels.

Plasma equilibrium control during slow plasma current quench with avoidance of plasma-wall interaction in JT-60U

NASA Astrophysics Data System (ADS)

Yoshino, R.; Nakamura, Y.; Neyatani, Y.

1997-08-01

In JT-60U a vertical displacement event (VDE) is observed during slow plasma current quench (Ip quench) for a vertically elongated divertor plasma with a single null. The VDE is generated by an error in the feedback control of the vertical position of the plasma current centre (ZJ). It has been perfectly avoided by improving the accuracy of the ZJ measurement in real time. Furthermore, plasma-wall interaction has been avoided successfully during slow Ip quench owing to the good performance of the plasma equilibrium control system

The Experiment of Modulated Toroidal Current on HT-7 and HT-6M Tokamak

NASA Astrophysics Data System (ADS)

Mao, Jian-shan; P, Phillips; Luo, Jia-rong; Xu, Yu-hong; Zhao, Jun-yu; Zhang, Xian-mei; Wan, Bao-nian; Zhang, Shou-yin; Jie, Yin-xian; Wu, Zhen-wei; Hu, Li-qun; Liu, Sheng-xia; Shi, Yue-jiang; Li, Jian-gang; HT-6M; HT-7 Group

2003-02-01

The Experiments of Modulated Toroidal Current were done on the HT-6M tokamak and HT-7 superconducting tokamak. The toroidal current was modulated by programming the Ohmic heating field. Modulation of the plasma current has been used successfully to suppress MHD activity in discharges near the density limit where large MHD m = 2 tearing modes were suppressed by sufficiently large plasma current oscillations. The improved Ohmic confinement phase was observed during modulating toroidal current (MTC) on the Hefei Tokamak-6M (HT-6M) and Hefei superconducting Tokamak-7 (HT-7). A toroidal frequency-modulated current, induced by a modulated loop voltage, was added on the plasma equilibrium current. The ratio of A.C. amplitude of plasma current to the main plasma current ΔIp/Ip is about 12%-30%. The different formats of the frequency-modulated toroidal current were compared.

Expression and high glucose-mediated regulation of K+ channel interacting protein 3 (KChIP3) and KV4 channels in retinal Müller glial cells.

PubMed

Chavira-Suárez, Erika; Sandoval, Alejandro; Felix, Ricardo; Lamas, Mónica

2011-01-14

Normal vision depends on the correct function of retinal neurons and glia and it is impaired in the course of diabetic retinopathy. Müller cells, the main glial cells of the retina, suffer morphological and functional alterations during diabetes participating in the pathological retinal dysfunction. Recently, we showed that Müller cells express the pleiotropic protein potassium channel interacting protein 3 (KChIP3), an integral component of the voltage-gated K(+) channels K(V)4. Here, we sought to analyze the role of KChIP3 in the molecular mechanisms underlying hyperglycemia-induced phenotypic changes in the glial elements of the retina. The expression and function of KChIp3 was analyzed in vitro in rat Müller primary cultures grown under control (5.6 mM) or high glucose (25 mM) (diabetic-like) conditions. We show the up-regulation of KChIP3 expression in Müller cell cultures under high glucose conditions and demonstrate a previously unknown interaction between the K(V)4 channel and KChIP3 in Müller cells. We show evidence for the expression of a 4-AP-sensitive transient outward voltage-gated K(+) current and an alteration in the inactivation of the macroscopic outward K(+) currents expressed in high glucose-cultured Müller cells. Our data support the notion that induction of KChIP3 and functional changes of K(V)4 channels in Müller cells could exert a physiological role in the onset of diabetic retinopathy. Copyright © 2010 Elsevier Inc. All rights reserved.

IpsA, a novel LacI-type regulator, is required for inositol-derived lipid formation in Corynebacteria and Mycobacteria.

PubMed

Baumgart, Meike; Luder, Kerstin; Grover, Shipra; Gätgens, Cornelia; Besra, Gurdyal S; Frunzke, Julia

2013-12-30

The development of new drugs against tuberculosis and diphtheria is focused on disrupting the biogenesis of the cell wall, the unique architecture of which confers resistance against current therapies. The enzymatic pathways involved in the synthesis of the cell wall by these pathogens are well understood, but the underlying regulatory mechanisms are largely unknown. Here, we characterize IpsA, a LacI-type transcriptional regulator conserved among Mycobacteria and Corynebacteria that plays a role in the regulation of cell wall biogenesis. IpsA triggers myo-inositol formation by activating ino1, which encodes inositol phosphate synthase. An ipsA deletion mutant of Corynebacterium glutamicum cultured on glucose displayed significantly impaired growth and presented an elongated cell morphology. Further studies revealed the absence of inositol-derived lipids in the cell wall and a complete loss of mycothiol biosynthesis. The phenotype of the C. glutamicum ipsA deletion mutant was complemented to different extend by homologs from Corynebacterium diphtheriae (dip1969) and Mycobacterium tuberculosis (rv3575), indicating the conserved function of IpsA in the pathogenic species. Additional targets of IpsA with putative functions in cell wall biogenesis were identified and IpsA was shown to bind to a conserved palindromic motif within the corresponding promoter regions. Myo-inositol was identified as an effector of IpsA, causing the dissociation of the IpsA-DNA complex in vitro. This characterization of IpsA function and of its regulon sheds light on the complex transcriptional control of cell wall biogenesis in the mycolata taxon and generates novel targets for drug development.

Validation of DAB2IP methylation and its relative significance in predicting outcome in renal cell carcinoma

PubMed Central

Zhao, Liang-Yun; Kapur, Payal; Wu, Kai-Jie; Wang, Bin; Yu, Yan-Hong; Liao, Bing; He, Da-Lin; Chen, Wei; Margulis, Vitaly; Hsieh, Jer-Tsong; Luo, Jun-Hang

2016-01-01

We have recently reported tumor suppressive role of DAB2IP in RCC development. In this study, We identified one CpG methylation biomarker (DAB2IP CpG1) located UTSS of DAB2IP that was associated with poor overall survival in a cohort of 318 ccRCC patients from the Cancer Genome Atlas (TCGA). We further validated the prognostic accuracy of DAB2IP CpG methylation by pyrosequencing quantitative methylation assay in 224 ccRCC patients from multiple Chinese centers (MCHC set), and 239 patients from University of Texas Southwestern Medical Center at Dallas (UTSW set) by using FFPE samples. DAB2IP CpG1 can predict the overall survival of patients in TCGA, MCHC, and UTSW sets independent of patient age, Fuhrman grade and TNM stage (all p<0.05). DAB2IP CpG1 successfully categorized patients into high-risk and low-risk groups with significant differences of clinical outcome in respective clinical subsets, regardless of age, sex, grade, stage, or race (HR: 1.63-7.83; all p<0.05). The detection of DAB2IP CpG1 methylation was minimally affected by ITH in ccRCC. DAB2IP mRNA expression was regulated by DNA methylation in vitro. DAB2IP CpG1 methylation is a practical and repeatable biomarker for ccRCC, which can provide prognostic value that complements the current staging system. PMID:27129174

Inversion of time-domain induced polarization data based on time-lapse concept

NASA Astrophysics Data System (ADS)

Kim, Bitnarae; Nam, Myung Jin; Kim, Hee Joon

2018-05-01

Induced polarization (IP) surveys, measuring overvoltage phenomena of the medium, are widely and increasingly performed not only for exploration of mineral resources but also for engineering applications. Among several IP survey methods such as time-domain, frequency-domain and spectral IP surveys, this study introduces a noble inversion method for time-domain IP data to recover the chargeability structure of target medium. The inversion method employs the concept of 4D inversion of time-lapse resistivity data sets, considering the fact that measured voltage in time-domain IP survey is distorted by IP effects to increase from the instantaneous voltage measured at the moment the source current injection starts. Even though the increase is saturated very fast, we can consider the saturated and instantaneous voltages as a time-lapse data set. The 4D inversion method is one of the most powerful method for inverting time-lapse resistivity data sets. Using the developed IP inversion algorithm, we invert not only synthetic but also field IP data to show the effectiveness of the proposed method by comparing the recovered chargeability models with those from linear inversion that was used for the inversion of the field data in a previous study. Numerical results confirm that the proposed inversion method generates reliable chargeability models even though the anomalous bodies have large IP effects.

Dependency of Tearing Mode Stability on Current and Pressure Profiles in DIII-D Hybrid Discharges

NASA Astrophysics Data System (ADS)

Kim, K.; Park, J. M.; Murakami, M.; La Haye, R. J.; Na, Y.-S.; SNU/ORAU; ORNL; Atomics, General; SNU; DIII-D Team

2016-10-01

Understanding the physics of the onset and evolution of tearing modes (TMs) in tokamak plasmas is important for high- β steady-state operation. Based on DIII-D steady-state hybrid experiments with accurate equilibrium reconstruction and well-measured plasma profiles, the 2/1 tearing mode can be more stable with increasing local current and pressure gradient at rational surface and with lower pressure peaking and plasma inductance. The tearing stability index Δ', estimated by the Rutherford equation with experimental mode growth rate was validated against Δ' calculated by linear eigenvalue solver (PEST3); preliminary comprehensive MHD modeling by NIMROD reproduced the TM onset reasonably well. We present a novel integrated modeling for the purpose of predicting TM onset in experiment by combining a model equilibrium reconstruction using IPS/FASTRAN, linear stability Δ' calculation using PEST3, and fitting formula for critical Δ' from NIMROD. Work supported in part by the US DoE under DE-AC05-06OR23100, DE-AC05-00OR22725, and DEFC02-04ER54698.

Electrochemical studies of quinine in surfactant media using hanging mercury drop electrode: a cyclic voltammetric study.

PubMed

Dar, Riyaz Ahmad; Brahman, Pradeep Kumar; Tiwari, Sweety; Pitre, Krishna Sadashiv

2012-10-01

The electrochemical behavior of quinine was investigated by cyclic voltammetry (CV) and square wave voltammetry (SWV) using surfactant. The reduction peak current of quinine increases remarkably in presence of 1% CTAB. Its electrochemical behavior is quasi-reversible in the Britton-Robinson buffers of pH 10.38 by exhibiting the well-defined single cathodic and anodic waves and the ratio of I(p)(a)/I(p)(c) approaching one at the scan rate of 500 mVs(-1). On the basis of CV, SWV and Coulometry, electrochemical reduction mechanism of quinine has been proposed which has shown that protonation occurs on the nitrogen of the quinoline moiety. Linearity was obtained when the peak currents (I(p)) were plotted against concentrations of quinine in the range of 30.0-230.0 ng mL(-1) with a detection limit of 0.132 ng mL(-1) in SWV and 90.0-630.0 ng mL(-1) with a detection limit of 0.238 ng mL(-1) in DPV. Fast and sensitive SWV has been applied for the quantitative analysis of quinine in bark of Cinchona sp. and in soft drinks and a good recovery was obtained. The accuracy and precision of the method are determined and validated statistically. No interferences from other food additives were observed. The relative standard deviation for intraday and interday assay was 0.89 and 0.73% (n=3) respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

Science, Medicine, and Intercessory Prayer

PubMed Central

Sloan, Richard P.; Ramakrishnan, Rajasekhar

2012-01-01

Among the many recent attempts to demonstrate the medical benefits of religious activity, the methodologically strongest seem to be studies of the effects of distant intercessory prayer (IP). In these studies, patients are randomly assigned to receive standard care or standard care plus the prayers or “healing intentions” of distant intercessors. Most of the scientific community has dismissed such research, but cavalier rejection of studies of IP is unwise, because IP studies appear to conform to the standards of randomized controlled trials (RCTs) and, as such, would have a significant advantage over observational investigations of associations between religious variables and health outcomes. As we demonstrate, however, studies of IP fail to meet the standards of RCTs in several critical respects. They fail to adequately measure and control exposure to prayer from others, which is likely to exceed IP and to vary widely from subject to subject, and whose magnitude is unknown. This supplemental prayer so greatly attenuates the differences between the treatment and control groups that sample sizes are too large to justify studies of IP. Further, IP studies generally do not specify the outcome variables, raising problems of multiple comparisons and Type 1 errors. Finally, these studies claim findings incompatible with current views of the physical universe and consciousness. Unless these problems are solved, studies of IP should not be conducted. PMID:17146135

Power Balance Modeling and Validation for ST Startup Using Local Helicity Injection

NASA Astrophysics Data System (ADS)

Barr, J. L.; Bodner, G. M.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Hinson, E. T.; Perry, J. M.; Reusch, J. A.; Schlossberg, D. J.

2015-11-01

Local Helicity Injection (LHI) uses localized current injectors for routine Ip<0.18 MA non-solenoidal startup on the Pegasus ST. A power-balance model is under development for predictive Ip t using helicity-balance to quantify LHI's effective current drive, Veff. Analytic formulas for low-A plasma inductance and vertical field are used to account for the inductive effects of dynamic shape evolution. These formulas are being validated against magnetic reconstructions of LHI discharges with varied shape evolutions. Initial results match experimental Ip t within 20 kA with assumed shaping and average resistivity (Spitzer, Te = 60 eV). Geometric effects and inductive drive provide 2.0 V along with Veff = 0.3 V to balance 1.1 V of resistive losses and 1.2 V inductive reactance to ramping Ip. The model is especially sensitive to resistivity when Te<150 eV. Initial Thomson Scattering results give core Te = 72 +/-22 eV, and at times suggest higher central electron energies. Spatial and temporal scans are underway to quantify LHI plasma resistivity and transport. MA-class startup in NSTX-U will require increased area (Ainj >= 40 cm2) LHI systems that play a larger role in current drive than geometric effects, with Veff dropping from >10 V to on-par with inductive effects. This regime is accessed in Pegasus at Ip ≅ 300 kA. Work supported by US DOE grants DE-FG02-96ER54375 and DE-SC0006928.

Magnetic novae

NASA Astrophysics Data System (ADS)

Zemko, Polina; Orio, Marina

2016-07-01

We present the results of optical and X-ray observations of two quiescent novae, V2491 Cyg and V4743 Sgr. Our observations suggest the intriguing possibility of localization of hydrogen burning in magnetic novae, in which accretion is streamed to the polar caps. V2491 Cyg was observed with Suzaku more than 2 years after the outburst and V4743 Sgr was observed with XMM Newton 2 and 3.5 years after maximum. In the framework of a monitoring program of novae previously observed as super soft X-ray sources we also obtained optical spectra of V4743 Sgr with the SALT telescope 11.5 years after the eruption and of V2491 Cyg with the 6m Big Azimutal Telescope 4 and 7 years post-outburst. In order to confirm the possible white dwarf spin period of V2491 Cyg measured in the Suzaku observations we obtained photometric data using the 90cm WIYN telescope at Kitt Peak and the 1.2 m telescope in Crimea. We found that V4743 Sgr is an intermediate polar (IP) and V2491 Cyg is a strong IP candidate. Both novae show modulation of their X-ray light curves and have X-ray spectra typical of IPs. The Suzaku and XMM Newton exposures revealed that the spectra of both novae have a very soft blackbody-like component with a temperature close to that of the hydrogen burning white dwarfs in their SSS phases, but with flux by at least two orders of magnitude lower, implying a possible shrinking of emitting regions in the thin atmosphere that is heated by nuclear burning underneath it. In quiescent IPs, independently of the burning, an ultrasoft X-ray flux component originates at times in the polar regions irradiated by the accretion column, but the soft component of V4743 Sgr disappeared in 2006, indicating that the origin may be different from accretion. We suggest it may have been due to an atmospheric temperature gradient on the white dwarf surface, or to continuing localized thermonuclear burning at the bottom of the envelope, before complete turn-off. The optical spectra of V2491 Cyg and V4743 Sgr showed the prominent He II 4686 A line and the Bowen blend, which indicate a hot region, with peak temperature in the ultraviolet range. This may be the same region that previously emitted supersoft X-rays, and later cooled shifting the peak of emission to the ultraviolet.

Rationale, Scenarios, and Profiles for the Application of the Internet Protocol Suite (IPS) in Space Operations

NASA Technical Reports Server (NTRS)

Benbenek, Daniel B.; Walsh, William

2010-01-01

This greenbook captures some of the current, planned and possible future uses of the Internet Protocol (IP) as part of Space Operations. It attempts to describe how the Internet Protocol is used in specific scenarios. Of primary focus is low-earth-orbit space operations, which is referred to here as the design reference mission (DRM). This is because most of the program experience drawn upon derives from this type of mission. Application profiles are provided. This includes parameter settings programs have proposed for sending IP datagrams over CCSDS links, the minimal subsets and features of the IP protocol suite and applications expected for interoperability between projects, and the configuration, operations and maintenance of these IP functions. Of special interest is capturing the lessons learned from the Constellation Program in this area, since that program included a fairly ambitious use of the Internet Protocol.

Network Upgrade for the SLC: Control System Modifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crane, M.; Mackenzie, R.; Sass, R.

2011-09-09

Current communications between the SLAC Linear Collider control system central host and the SLCmicros is built upon the SLAC developed SLCNET communication hardware and protocols. We will describe how the Internet Suite of protocols (TCP/IP) are used to replace the SLCNET protocol interface. The major communication pathways and their individual requirements are described. A proxy server is used to reduce the number of total system TCP/IP connections. The SLCmicros were upgraded to use Ethernet and TCP/IP as well as SLCNET. Design choices and implementation experiences are addressed.

A comparative study of ChIP-seq sequencing library preparation methods.

PubMed

Sundaram, Arvind Y M; Hughes, Timothy; Biondi, Shea; Bolduc, Nathalie; Bowman, Sarah K; Camilli, Andrew; Chew, Yap C; Couture, Catherine; Farmer, Andrew; Jerome, John P; Lazinski, David W; McUsic, Andrew; Peng, Xu; Shazand, Kamran; Xu, Feng; Lyle, Robert; Gilfillan, Gregor D

2016-10-21

ChIP-seq is the primary technique used to investigate genome-wide protein-DNA interactions. As part of this procedure, immunoprecipitated DNA must undergo "library preparation" to enable subsequent high-throughput sequencing. To facilitate the analysis of biopsy samples and rare cell populations, there has been a recent proliferation of methods allowing sequencing library preparation from low-input DNA amounts. However, little information exists on the relative merits, performance, comparability and biases inherent to these procedures. Notably, recently developed single-cell ChIP procedures employing microfluidics must also employ library preparation reagents to allow downstream sequencing. In this study, seven methods designed for low-input DNA/ChIP-seq sample preparation (Accel-NGS® 2S, Bowman-method, HTML-PCR, SeqPlex™, DNA SMART™, TELP and ThruPLEX®) were performed on five replicates of 1 ng and 0.1 ng input H3K4me3 ChIP material, and compared to a "gold standard" reference PCR-free dataset. The performance of each method was examined for the prevalence of unmappable reads, amplification-derived duplicate reads, reproducibility, and for the sensitivity and specificity of peak calling. We identified consistent high performance in a subset of the tested reagents, which should aid researchers in choosing the most appropriate reagents for their studies. Furthermore, we expect this work to drive future advances by identifying and encouraging use of the most promising methods and reagents. The results may also aid judgements on how comparable are existing datasets that have been prepared with different sample library preparation reagents.

The effectiveness of augmented versus standard individual placement and support programs in terms of employment: a systematic literature review.

PubMed

Dewa, Carolyn S; Loong, Desmond; Trojanowski, Lucy; Bonato, Sarah

2018-04-01

The Individual Placement and Support (IPS) program is a well-studied vocational rehabilitation program. Although it is more effective than usual care, it is not effective for everyone. This offers an opportunity for program improvement. This systematic literature review examines the state of knowledge regarding the effectiveness of augmented versus standard IPS for people with severe mental illness (SMI). We address the questions, "What IPS augmentations have been tested?" and "What is the evidence for the effectiveness of augmented IPS versus standard IPS in terms of employment?" This systematic literature review used publically available peer-reviewed studies published between January 2002 and January 2016 in either: (1) Medline Current, (2) Medline In-process, (3) PsycINFO, (4) Econlit or (5) Web of Science. 5718 unique citations were identified; seven articles from five studies were included. Of these studies, four were rated as having moderate risk of bias and one as having high risk. The results suggest that augmentations of IPS focusing on cognitive and psychosocial skills training, may have additional effects to standard IPS. Areas in need of further research related to the process and targeting of those interventions are discussed.

Image quality evaluation for smart-phone displays at lighting levels of indoor and outdoor conditions

NASA Astrophysics Data System (ADS)

Gong, Rui; Xu, Haisong; Wang, Binyu; Luo, Ming Ronnier

2012-08-01

The image quality of two active matrix organic light emitting diode (AMOLED) smart-phone displays and two in-plane switching (IPS) ones was visually assessed at two levels of ambient lighting conditions corresponding to indoor and outdoor applications, respectively. Naturalness, colorfulness, brightness, contrast, sharpness, and overall image quality were evaluated via psychophysical experiment by categorical judgment method using test images selected from different application categories. The experimental results show that the AMOLED displays perform better on colorfulness because of their wide color gamut, while the high pixel resolution and high peak luminance of the IPS panels help the perception of brightness, contrast, and sharpness. Further statistical analysis of ANOVA indicates that ambient lighting levels have significant influences on the attributes of brightness and contrast.

Post-activation Potentiation in Propulsive Force after Specific Swimming Strength Training.

PubMed

Barbosa, A C; Barroso, R; Andries, O

2016-04-01

We investigated whether a conditioning activity (8×12.5 m with 2.5 min-interval using both hand paddles and parachute) induced post-activation potentiation in swimming propulsive force and whether a swimmer's force level affected a post-activation potentiation response. 8 competitive swimmers (5 males and 3 females, age: 18.4±1.3 years; IPS=796±56) performed a 10 s maximum tethered swimming test 8 and 4 min before (the highest value was considered as PRE), and 2.5 and 6.5 min after (POST1 and POST2, respectively) the conditioning activity. Rate of force development was not affected, but peak force in POST1 (p=0.02) and impulse in both POST1 (p=0.007) and POST2 (p=0.004) were reduced. Possibly the conditioning activity induced greater fatigue than post-activation potentiation benefits. For instance, the number of repetitions might have been excessive, and rest intervals between the conditioning activity and POST1 and POST2 were possibly too short. There were positive correlations between PRE peak force and changes in peak force and rate of force development. Although conditioning activity was detrimental, positive correlations suggest that weaker swimmers experience a deterioration of performance more than the stronger ones. This conditioning activity is not recommended for swimmers with the current competitive level before a competitive event. © Georg Thieme Verlag KG Stuttgart · New York.

IpsA, a novel LacI-type regulator, is required for inositol-derived lipid formation in Corynebacteria and Mycobacteria

PubMed Central

2013-01-01

Background The development of new drugs against tuberculosis and diphtheria is focused on disrupting the biogenesis of the cell wall, the unique architecture of which confers resistance against current therapies. The enzymatic pathways involved in the synthesis of the cell wall by these pathogens are well understood, but the underlying regulatory mechanisms are largely unknown. Results Here, we characterize IpsA, a LacI-type transcriptional regulator conserved among Mycobacteria and Corynebacteria that plays a role in the regulation of cell wall biogenesis. IpsA triggers myo-inositol formation by activating ino1, which encodes inositol phosphate synthase. An ipsA deletion mutant of Corynebacterium glutamicum cultured on glucose displayed significantly impaired growth and presented an elongated cell morphology. Further studies revealed the absence of inositol-derived lipids in the cell wall and a complete loss of mycothiol biosynthesis. The phenotype of the C. glutamicum ipsA deletion mutant was complemented to different extend by homologs from Corynebacterium diphtheriae (dip1969) and Mycobacterium tuberculosis (rv3575), indicating the conserved function of IpsA in the pathogenic species. Additional targets of IpsA with putative functions in cell wall biogenesis were identified and IpsA was shown to bind to a conserved palindromic motif within the corresponding promoter regions. Myo-inositol was identified as an effector of IpsA, causing the dissociation of the IpsA-DNA complex in vitro. Conclusions This characterization of IpsA function and of its regulon sheds light on the complex transcriptional control of cell wall biogenesis in the mycolata taxon and generates novel targets for drug development. PMID:24377418

Anomalous current diffusion and improved confinement in the HT-6M tohamak

NASA Astrophysics Data System (ADS)

Gao, X.; Li, J. G.; Wan, Y. X.; Huo, Y. P.; Guo, W. K.; Fan, S. P.; Yu, C. X.; Luo, J. R.; Yin, F. X.; Meng, Y. D.; Zheng, L.; Yin, F.; Lin, B. L.; Zhang, S. Y.; Wang, S. Y.; Lu, H. J.; Liu, S. X.; Tong, X. D.; Ding, L. C.; Wu, Z. Y.; Yin, X. J.; Guo, Q. L.; Gong, X. Z.; Wu, X. C.; Zhao, J. Y.; Xi, J. S.

1994-10-01

Current diffusion was studied during edge ohmic heating (EOH) experiments in the HT-6M tokamak. The EOH power system makes the plasma current linearly ramp up from an initial steady state ( Ip=55kA) to a second steady state ( Ip=60kA) at a fast ramp rate of 12 MA/s. A stable discharge of an improved confinement was observed experimentally in the HT-6M tokamak after the plasma current was ramped to rise rapidly to a second steady state. The plasma current is ramped up much faster than both the classical skin time and neoclassical skin time. Fast current ramp up increases the anomalous current diffusion. The measured values of {β P+l i}/{2} and the soft X-ray sawtooth inversion radius imply the anomalous current penetration. The mechanism of anomalous penetration and improved confinement is discussed.

Understanding the Relationship Between Female Sex Workers and Their Intimate Partners: Lessons and Initial Findings From Participatory Research in North Karnataka, South India.

PubMed

Bhattacharjee, Parinita; Campbell, Linda; Thalinja, Raghavendra; Nair, Sapna; Doddamane, Mahesh; Ramanaik, Satyanarayana; Isac, Shajy; Beattie, Tara S

2018-04-01

While traditional HIV prevention programs with female sex workers (FSWs) in Karnataka, India, have focused on reducing HIV transmission between FSWs and clients through increased condom use, these programs have not fully addressed the transmission risk between FSWs and their nonpaying intimate partners (IPs). Condom use is infrequent and violence is recurrent in these relationships: Furthermore, there is little evidence on the precise nature of FSW-IP relationships. Our study addresses this knowledge gap to inform HIV programs targeted at FSWs. A series of workshops, using participatory tools, was held to explore FSW-IP relationships; 31 FSWs and 37 IPs participated. Three aspects of FSW-IP relationships were examined: how FSWs and IPs understand and interpret their relationships, factors influencing condom use, and the role of violence and its consequences. FSWs wish to be perceived as their IPs' wives, while IPs expect their FSW partners to accept their dominance in the relationship. Nonuse of condoms signals fidelity and elevates the status of the relationship almost to that of marriage, which helps FSWs enter the category of "good" (married) women. Tolerating and accepting violence in these relationships is normative, as in other marital relationships; IPs justify violence as necessary to establish and maintain their power within the relationship. Both FSWs and IPs value their relationships despite the high degree of risk posed by low condom use and high levels of violence. Implications for program design include addressing current norms around masculinity and gender roles, and improving communication within relationships.

Correlation between lifetime heterogeneity and kinetics heterogeneity during chlorophyll fluorescence induction in leaves: 1. Mono-frequency phase and modulation analysis reveals a conformational change of a PSII pigment complex during the IP thermal phase.

PubMed

Moise, Nicolae; Moya, Ismaël

2004-06-28

The relationship between the fluorescence lifetime (tau) and yield (Phi) obtained in phase and modulation fluorometry at 54 MHz during the chlorophyll fluorescence induction in dark-adapted leaves under low actinic light has been investigated. Three typical phases have been identified: (i) linear during the OI photochemical rise, (ii) convex curvature during the subsequent IP thermal rise, and (iii) linear during the PS slow decay. A similar relationship has been obtained in the fluorescence induction for the fluorescence yield measured at 685 nm plotted versus the fluorescence yield measured at 735 nm. A spectrally resolved analysis shows that the curvature of the tau-Phi relationship is not due to chlorophyll fluorescence reabsorption effects. Several other hypotheses are discussed and we conclude that the curvature of the tau-Phi relationship is due to a variable and transitory nonphotochemical quenching. We tentatively propose that this quenching results from a conformational change of a pigment-protein complex of Photosystem II core antenna during the IP phase and could explain both spectral and temporal transitory changes of the fluorescence. A variable blue shift of the 685 nm peak of the fluorescence spectrum during the IP phase has been observed, supporting this hypothesis.

Activation of D2 autoreceptors alters cocaine-induced locomotion and slows down local field oscillations in the rat ventral tegmental area.

PubMed

Koulchitsky, Stanislav; Delairesse, Charlotte; Beeken, Thom; Monteforte, Alexandre; Dethier, Julie; Quertemont, Etienne; Findeisen, Rolf; Bullinger, Eric; Seutin, Vincent

2016-09-01

Psychoactive substances affecting the dopaminergic system induce locomotor activation and, in high doses, stereotypies. Network mechanisms underlying the shift from an active goal-directed behavior to a "seemingly purposeless" stereotypic locomotion remain unclear. In the present study we sought to determine the relationships between the behavioral effects of dopaminergic drugs and their effects on local field potentials (LFPs), which were telemetrically recorded within the ventral tegmental area (VTA) of freely moving rats. We used the D2/D3 agonist quinpirole in a low, autoreceptor-selective (0.1 mg/kg, i.p.) and in a high (0.5 mg/kg, i.p.) dose, and a moderate dose of cocaine (10 mg/kg, i.p.). In the control group, power spectrum analysis revealed a prominent peak of LFP power in the theta frequency range during active exploration. Cocaine alone stimulated locomotion, but had no significant effect on the peak of the LFP power. In contrast, co-administration of low dose quinpirole with cocaine markedly altered the pattern of locomotion, from goal-directed exploratory behavior to recurrent motion resembling locomotor stereotypy. This behavioral effect was accompanied by a shift of the dominant theta power toward a significantly lower (by ∼15%) frequency. High dose quinpirole also provoked an increased locomotor activity with signs of behavioral stereotypies, and also induced a shift of the dominant oscillation frequency toward the lower range. These results demonstrate a correlation between the LFP oscillation frequency within the VTA and a qualitative aspect of locomotor behavior, perhaps due to a variable level of coherence of this region with its input or output areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

NFI Transcription Factors Interact with FOXA1 to Regulate Prostate-Specific Gene Expression

PubMed Central

Elliott, Amicia D.; DeGraff, David J.; Anderson, Philip D.; Anumanthan, Govindaraj; Yamashita, Hironobu; Sun, Qian; Friedman, David B.; Hachey, David L.; Yu, Xiuping; Sheehan, Jonathan H.; Ahn, Jung-Mo; Raj, Ganesh V.; Piston, David W.; Gronostajski, Richard M.; Matusik, Robert J.

2014-01-01

Androgen receptor (AR) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between AR and forkhead box (FOX) transcription factors, particularly FOXA1. We sought to identity additional FOXA1 binding partners that may mediate prostate-specific gene expression. Here we identify the nuclear factor I (NFI) family of transcription factors as novel FOXA1 binding proteins. All four family members (NFIA, NFIB, NFIC, and NFIX) can interact with FOXA1, and knockdown studies in androgen-dependent LNCaP cells determined that modulating expression of NFI family members results in changes in AR target gene expression. This effect is probably mediated by binding of NFI family members to AR target gene promoters, because chromatin immunoprecipitation (ChIP) studies found that NFIB bound to the prostate-specific antigen enhancer. Förster resonance energy transfer studies revealed that FOXA1 is capable of bringing AR and NFIX into proximity, indicating that FOXA1 facilitates the AR and NFI interaction by bridging the complex. To determine the extent to which NFI family members regulate AR/FOXA1 target genes, motif analysis of publicly available data for ChIP followed by sequencing was undertaken. This analysis revealed that 34.4% of peaks bound by AR and FOXA1 contain NFI binding sites. Validation of 8 of these peaks by ChIP revealed that NFI family members can bind 6 of these predicted genomic elements, and 4 of the 8 associated genes undergo gene expression changes as a result of individual NFI knockdown. These observations suggest that NFI regulation of FOXA1/AR action is a frequent event, with individual family members playing distinct roles in AR target gene expression. PMID:24801505

Piñon mortality from 2001 to 2005: Causes and management strategies

Treesearch

Tom Eager

2008-01-01

(Please note, this is an abstract only) Pinon mortality in the pinon-juniper and pinon-sage types of the Southwest peaked in 2003 following several years of winter drought. The majority of the droughtweakened trees died from pinon ips bark beetle attacks, but twig beetles also played a role. Forest Service aerial surveyors estimate more than 50 million pinon trees died...

Team Faces Tough Odds to Implement New Phone Network | Poster

Cancer.gov

It was a Saturday, in the final stretch of winter in late February, and the temperature peaked to a pleasant 66 degrees. Many people were outside enjoying the spring-like weather; however, the Voice over Internet Protocol (VoIP) Deployment Team was hard at work at Industry Lane. The team of 10 was installing the new voice-only network, including deploying 145 phones, switching

High-space resolution imaging plate analysis of extreme ultraviolet (EUV) light from tin laser-produced plasmas

NASA Astrophysics Data System (ADS)

Musgrave, Christopher S. A.; Murakami, Takehiro; Ugomori, Teruyuki; Yoshida, Kensuke; Fujioka, Shinsuke; Nishimura, Hiroaki; Atarashi, Hironori; Iyoda, Tomokazu; Nagai, Keiji

2017-03-01

With the advent of high volume manufacturing capabilities by extreme ultraviolet lithography, constant improvements in light source design and cost-efficiency are required. Currently, light intensity and conversion efficiency (CE) measurments are obtained by charged couple devices, faraday cups etc, but also phoshpor imaging plates (IPs) (BaFBr:Eu). IPs are sensitive to light and high-energy species, which is ideal for studying extreme ultraviolet (EUV) light from laser produced plasmas (LPPs). In this work, we used IPs to observe a large angular distribution (10°-90°). We ablated a tin target by high-energy lasers (1064 nm Nd:YAG, 1010 and 1011 W/cm2) to generate the EUV light. The europium ions in the IP were trapped in a higher energy state from exposure to EUV light and high-energy species. The light intensity was angular dependent; therefore excitation of the IP depends on the angle, and so highly informative about the LPP. We obtained high-space resolution (345 μm, 0.2°) angular distribution and grazing spectrometer (5-20 nm grate) data simultaneously at different target to IP distances (103 mm and 200 mm). Two laser systems and IP types (BAS-TR and BAS-SR) were also compared. The cosine fitting values from the IP data were used to calculate the CE to be 1.6% (SD ± 0.2) at 13.5 nm 2% bandwidth. Finally, a practical assessment of IPs and a damage issue are disclosed.

The role of interplanetary shock orientation on SC/SI rise time and geoeffectiveness

NASA Astrophysics Data System (ADS)

Selvakumaran, R.; Veenadhari, B.; Ebihara, Y.; Kumar, Sandeep; Prasad, D. S. V. V. D.

2017-03-01

Interplanetary (IP) shocks interact with the Earth's magnetosphere, resulting in compression of the magnetosphere which in turn increases the Earth's magnetic field termed as Sudden commencement/Sudden impulse (SC/SI). Apart from IP shock speed and solar wind dynamic pressure, IP shock orientation angle also plays a major role in deciding the SC rise time. In the present study, the IP shock orientation angle and SC/SI rise time for 179 IP shocks are estimated which occurred during solar cycle 23. More than 50% of the Shock orientations are in the range of 140°-160°. The SC/SI rise time decreases with the increase in the orientation angle and IP shock speed. In this work, the type of IP shocks i.e., Radio loud (RL) and Radio quiet (RQ) are examined in connection with SC/SI rise time. The RL associated IP shock speeds show a better correlation than RQ shocks with SC/SI rise time irrespective of the orientation angle. Magnetic Cloud (MC) associated shocks dominate in producing less rise time when compared to Ejecta (EJ) shocks. Magneto hydrodynamic (MHD) simulations are used for three different IP shock orientation categories to see the importance of orientation angle in determining the geoeffectiveness. Simulations results reveal that shocks hitting parallel to the magnetosphere are more geoeffective as compared to oblique shocks by means of change in magnetic field, pressure and Field Aligned Current (FAC).

Plasma current ramp-up by lower hybrid wave using innovative antennas on TST-2

NASA Astrophysics Data System (ADS)

Takase, Yuichi; Ejiri, Akira; Moeller, Charles; Roidl, Benedikt; Shinya, Takahiro; Tsujii, Naoto; Yajima, Satoru; Yamazaki, Hibiki; Kitayama, Akichika; Matsumoto, Naoki; Sato, Akito; Sonehara, Masateru; Takahashi, Wataru; Tajiri, Yoshiyuki; Takei, Yuki; Togashi, Hiro; Toida, Kazuya; Yoshida, Yusuke

2016-10-01

Non-inductive plasma current (Ip) ramp-up by RF power in the lower hybrid frequency range is being studied on the TST-2 spherical tokamak (R = 0.36 m, a = 0.23 m, Bt = 0.3 T, Ip = 0.1 MA). Up to 400 kW of RF power is available at a frequency of 200 MHz. An innovative antenna called the capacitively-coupled combline (CCC) antenna was developed to excite a sharp, highly directional traveling wave with the electric field polarized in the toroidal direction. It is an array of resonant circuit elements made of capacitance and inductance, coupled to neighboring elements by mutual capacitance. Two CCC antennas are installed in TST-2, a 13-element outboard-launch antenna and a 6-element top-launch antenna. The latter was installed in March 2016 to improve accessibility to the core and to achieve single-pass damping. The suspected wave power loss in the scrape-off layer plasma should also be avoided. Ip ramp-up to 25 kA has been achieved so far. An upgrade of the Bt power supply is planned to take advantage of the observed improvement of Ip ramp-up with Bt. Higher Bt for longer pulses should improve the Ip ramp-up efficiency by improving wave accessibility and by reducing prompt orbit losses of energetic electrons.

Parallel Inhibition of Dopamine Amacrine Cells and Intrinsically Photosensitive Retinal Ganglion Cells in a Non-Image-Forming Visual Circuit of the Mouse Retina

PubMed Central

Vuong, Helen E.; Hardi, Claudia N.; Barnes, Steven

2015-01-01

An inner retinal microcircuit composed of dopamine (DA)-containing amacrine cells and melanopsin-containing, intrinsically photosensitive retinal ganglion cells (M1 ipRGCs) process information about the duration and intensity of light exposures, mediating light adaptation, circadian entrainment, pupillary reflexes, and other aspects of non-image-forming vision. The neural interaction is reciprocal: M1 ipRGCs excite DA amacrine cells, and these, in turn, feed inhibition back onto M1 ipRGCs. We found that the neuropeptide somatostatin [somatotropin release inhibiting factor (SRIF)] also inhibits the intrinsic light response of M1 ipRGCs and postulated that, to tune the bidirectional interaction of M1 ipRGCs and DA amacrine cells, SRIF amacrine cells would provide inhibitory modulation to both cell types. SRIF amacrine cells, DA amacrine cells, and M1 ipRGCs form numerous contacts. DA amacrine cells and M1 ipRGCs express the SRIF receptor subtypes sst2A and sst4 respectively. SRIF modulation of the microcircuit was investigated with targeted patch-clamp recordings of DA amacrine cells in TH–RFP mice and M1 ipRGCs in OPN4–EGFP mice. SRIF increases K+ currents, decreases Ca2+ currents, and inhibits spike activity in both cell types, actions reproduced by the selective sst2A agonist L-054,264 (N-[(1R)-2-[[[(1S*,3R*)-3-(aminomethyl)cyclohexyl]methyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]spiro[1H-indene-1,4′-piperidine]-1′-carboxamide) in DA amacrine cells and the selective sst4 agonist L-803,087 (N2-[4-(5,7-difluoro-2-phenyl-1H-indol-3-yl)-1-oxobutyl]-l-arginine methyl ester trifluoroacetate) in M1 ipRGCs. These parallel actions of SRIF may serve to counteract the disinhibition of M1 ipRGCs caused by SRIF inhibition of DA amacrine cells. This allows the actions of SRIF on DA amacrine cells to proceed with adjusting retinal DA levels without destabilizing light responses by M1 ipRGCs, which project to non-image-forming targets in the brain. SIGNIFICANCE STATEMENT Amacrine cells form multiple microcircuits in the inner retina to mediate visual processing, although their organization and function remain incompletely understood. The somatostatin [somatotropin release inhibiting factor (SRIF)]- and dopamine (DA)-releasing amacrine cells act globally, and, in this study, they are shown to interact and modulate the light response of intrinsically photosensitive retinal ganglion cells (ipRGCs). SRIF amacrine cells target both DA amacrine cells and M1 ipRGCs for inhibition. The parallel actions of SRIF may serve to compensate for the loss of DA-mediated inhibition of M1 ipRGCs. This inhibitory tuning is of particular importance because the DA system mediates a broad range of light adaptational actions in the retina and M1 ipRGCs project to brain areas that influence sleep, mood, cognition, circadian entrainment, and pupillary reflexes. PMID:26631476

A decentralized software bus based on IP multicas ting

NASA Technical Reports Server (NTRS)

Callahan, John R.; Montgomery, Todd

1995-01-01

We describe decentralized reconfigurable implementation of a conference management system based on the low-level Internet Protocol (IP) multicasting protocol. IP multicasting allows low-cost, world-wide, two-way transmission of data between large numbers of conferencing participants through the Multicasting Backbone (MBone). Each conference is structured as a software bus -- a messaging system that provides a run-time interconnection model that acts as a separate agent (i.e., the bus) for routing, queuing, and delivering messages between distributed programs. Unlike the client-server interconnection model, the software bus model provides a level of indirection that enhances the flexibility and reconfigurability of a distributed system. Current software bus implementations like POLYLITH, however, rely on a centralized bus process and point-to-point protocols (i.e., TCP/IP) to route, queue, and deliver messages. We implement a software bus called the MULTIBUS that relies on a separate process only for routing and uses a reliable IP multicasting protocol for delivery of messages. The use of multicasting means that interconnections are independent of IP machine addresses. This approach allows reconfiguration of bus participants during system execution without notifying other participants of new IP addresses. The use of IP multicasting also permits an economy of scale in the number of participants. We describe the MULITIBUS protocol elements and show how our implementation performs better than centralized bus implementations.

Creation of a competency-based professional development program for infection preventionists guided by the APIC Competency Model: steps in the process.

PubMed

Bernard, Heather; Hackbarth, Diana; Olmsted, Russell N; Murphy, Denise

2018-06-07

Infection Preventionists have varying levels of educational preparation. Many have no prior experience in IP. The diversity makes design of professional development programs challenging. Recent surveys suggest that only about half of practicing IPs are board certified. There is an urgent need to employ competent IP's to drive improvement in patient outcomes. This is a project that utilized the APIC Competency Model to create a professional development program characterizing three career stages. Methods included a review of literature on professional development; a survey of IP competence; an assessment of job descriptions and performance evaluations; and a crosswalk of IP competencies. The professional development program includes competency - based IP job descriptions and performance evaluations for each career stage; a professional portfolio; and a toolkit for supervisors. Participants agreed that application of the model resulted in tools which are more closely aligned with current roles for IPs; and increased satisfaction and motivation with the new program. Competent and knowledgeable IP's are crucial to optimizing efficacy of IPC programs. A professional development program has the potential to guide staff orientation, improve satisfaction and retention, improve patient outcomes and promote a positive trajectory in advancing practice. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Spectral emission measurements of lithium on the lithium tokamak experiment.

PubMed

Gray, T K; Biewer, T M; Boyle, D P; Granstedt, E M; Kaita, R; Maingi, R; Majeski, R P

2012-10-01

There has been a long-standing collaboration between ORNL and PPPL on edge and boundary layer physics. As part of this collaboration, ORNL has a large role in the instrumentation and interpretation of edge physics in the lithium tokamak experiment (LTX). In particular, a charge exchange recombination spectroscopy (CHERS) diagnostic is being designed and undergoing staged testing on LTX. Here we present results of passively measured lithium emission at 5166.89 A in LTX in anticipation of active spectroscopy measurements, which will be enabled by the installation of a neutral beam in 2013. Preliminary measurements are made in transient LTX plasmas with plasma current, I(p) < 70 kA, ohmic heating power, P(oh) ∼ 0.3 MW and discharge lifetimes of 10-15 ms. Measurements are made with a short focal length spectrometer and optics similar to the CHERS diagnostics on NSTX [R. E. Bell, Rev. Sci. Instrum. 68(2), 1273-1280 (1997)]. These preliminary measurements suggest that even without the neutral beam for active spectroscopy, there is sufficient passive lithium emission to allow for line-of-sight profile measurements of ion temperature, T(i); toroidal velocity and v(t). Results show peak T(i) = 70 eV and peak v(t) = 45 km/s were reached 10 ms into the discharge.

Non-solenoidal startup and low-β operations in Pegasus

NASA Astrophysics Data System (ADS)

Schlossberg, D. J.; Battaglia, D. J.; Bongard, M. W.; Fonck, R. J.; Redd, A. J.

2009-11-01

Non-solenoidal startup using point-source DC helicity injectors (plasma guns) has been achieved in the Pegasus Toroidal Experiment for plasmas with Ip in excess of 100 kA using Iinj<4,A. The maximum achieved Ip tentatively scales as √ITFIinj/w, where w is the radial thickness of the gun-driven edge. The Ip limits appear to conform to a simple stationary model involving helicity conservation and Taylor relaxation. However, observed MHD activity reveals the additional dynamics of the relaxation process, evidenced by intermittent bursts of n=1 activity correlated with rapid redistribution of the current channel. Recent upgrades to the gun system provide higher helicity injection rates, smaller w, a more constrained gun current path, and more precise diagnostics. Experimental goals include extending parametric scaling studies, determining the conditions where parallel conduction losses dominate the helicity dissipation, and building the physics understanding of helicity injection to confidently design gun systems for larger, future tokamaks.

Caffeine protects against experimental acute pancreatitis by inhibition of inositol 1,4,5-trisphosphate receptor-mediated Ca2+ release

PubMed Central

Huang, Wei; Cane, Matthew C; Mukherjee, Rajarshi; Szatmary, Peter; Zhang, Xiaoying; Elliott, Victoria; Ouyang, Yulin; Chvanov, Michael; Latawiec, Diane; Wen, Li; Booth, David M; Haynes, Andrea C; Petersen, Ole H; Tepikin, Alexei V; Criddle, David N

2017-01-01

Objective Caffeine reduces toxic Ca2+ signals in pancreatic acinar cells via inhibition of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated signalling, but effects of other xanthines have not been evaluated, nor effects of xanthines on experimental acute pancreatitis (AP). We have determined effects of caffeine and its xanthine metabolites on pancreatic acinar IP3R-mediated Ca2+ signalling and experimental AP. Design Isolated pancreatic acinar cells were exposed to secretagogues, uncaged IP3 or toxins that induce AP and effects of xanthines, non-xanthine phosphodiesterase (PDE) inhibitors and cyclic adenosine monophosphate and cyclic guanosine monophosphate (cAMP/cGMP) determined. The intracellular cytosolic calcium concentration ([Ca2+]C), mitochondrial depolarisation and necrosis were assessed by confocal microscopy. Effects of xanthines were evaluated in caerulein-induced AP (CER-AP), taurolithocholic acid 3-sulfate-induced AP (TLCS-AP) or palmitoleic acid plus ethanol-induced AP (fatty acid ethyl ester AP (FAEE-AP)). Serum xanthines were measured by liquid chromatography-mass spectrometry. Results Caffeine, dimethylxanthines and non-xanthine PDE inhibitors blocked IP3-mediated Ca2+ oscillations, while monomethylxanthines had little effect. Caffeine and dimethylxanthines inhibited uncaged IP3-induced Ca2+ rises, toxin-induced Ca2+ release, mitochondrial depolarisation and necrotic cell death pathway activation; cAMP/cGMP did not inhibit toxin-induced Ca2+ rises. Caffeine significantly ameliorated CER-AP with most effect at 25 mg/kg (seven injections hourly); paraxanthine or theophylline did not. Caffeine at 25 mg/kg significantly ameliorated TLCS-AP and FAEE-AP. Mean total serum levels of dimethylxanthines and trimethylxanthines peaked at >2 mM with 25 mg/kg caffeine but at <100 µM with 25 mg/kg paraxanthine or theophylline. Conclusions Caffeine and its dimethylxanthine metabolites reduced pathological IP3R-mediated pancreatic acinar Ca2+ signals but only caffeine ameliorated experimental AP. Caffeine is a suitable starting point for medicinal chemistry. PMID:26642860

Limitations and possibilities of low cell number ChIP-seq

PubMed Central

2012-01-01

Background Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting material in the range of 1–20 million cells per immunoprecipitation, and remain a bottleneck to the acquisition of biologically relevant epigenetic data. Using a ChIP-seq protocol optimised for low cell numbers (down to 100,000 cells / IP), we examined the performance of the ChIP-seq technique on a series of decreasing cell numbers. Results We present an enhanced native ChIP-seq method tailored to low cell numbers that represents a 200-fold reduction in input requirements over existing protocols. The protocol was tested over a range of starting cell numbers covering three orders of magnitude, enabling determination of the lower limit of the technique. At low input cell numbers, increased levels of unmapped and duplicate reads reduce the number of unique reads generated, and can drive up sequencing costs and affect sensitivity if ChIP is attempted from too few cells. Conclusions The optimised method presented here considerably reduces the input requirements for performing native ChIP-seq. It extends the applicability of the technique to isolated primary cells and rare cell populations (e.g. biobank samples, stem cells), and in many cases will alleviate the need for cell culture and any associated alteration of epigenetic marks. However, this study highlights a challenge inherent to ChIP-seq from low cell numbers: as cell input numbers fall, levels of unmapped sequence reads and PCR-generated duplicate reads rise. We discuss a number of solutions to overcome the effects of reducing cell number that may aid further improvements to ChIP performance. PMID:23171294

Procedural volume and structure of interventional pulmonary fellowships: a survey of fellows and fellowship program directors.

PubMed

Yarmus, Lonny; Feller-Kopman, David; Imad, Melhem; Kim, Stephanie; Lee, Hans J

2013-09-01

Current interventional pulmonary (IP) procedural guidelines for competency are based on expert opinion. There are few objective data to support competency metrics for IP procedures. This survey reports procedural volume during IP fellowships to help define new standards in training and curriculum development. A web-based survey was developed to evaluate IP training procedural volume. The survey was administered to all US and Canadian IP fellowship directors and graduates in training from 2006 to 2011. The survey inquired about all diagnostic and therapeutic procedures performed during the specialized year of IP training. Questions regarding the training program structure were collected and analyzed. There was a 92.5% fellow response rate (37 of 40) and 77% fellowship director response rate (10 of 13) from programs in existence at the time of the survey. Procedural volume was consistent between fellowship directors and graduates (P = .64). Although there was a wide range of procedural volume and types of procedures between different programs, the procedural mean volumes were all significantly higher than the American College of Chest Physicians (ACCP) and American Thoracic Society/European Respiratory Society (ATS/ERS) guideline recommendations (P < .005). US and Canadian IP fellowships produce fellows with variable procedural volumes; however, these are significantly higher than ACCP and ATS/ERS guidelines for most programs and procedures. With a uniform training curriculum being adopted by the majority of IP fellowship programs in the United States and Canada, as well as data showing improved core knowledge in IP fellows undergoing a dedicated year of additional training, further metrics examining the impact of advanced IP training on patient outcomes are needed.

Hybrid model for wireless mobility management using IPv6

NASA Astrophysics Data System (ADS)

Howie, Douglas P.; Sun, Junzhao; Koivisto, Antti T.

2001-07-01

Within the coming decade, there will be a dramatic increase in the availability of inexpensive, computationally powerful mobile devices running applications which use the Internet Protocol (IP) to access multimedia services over broad-band wireless connections. To this end, there has been extensive research and standardization in the areas of Mobile IP and IPv6. The purpose of this paper is to apply this work to the issues involved in designing a mobility model able to adapt to different wireless mobile IP scenarios. We describe the usefulness of this model in the 4th generation mobile multimedia systems to come. This new model has been synthesized through a comparative analysis of current mobile IP models where particular attention has been given to the problems of mobile IP handoff and mobility management and their impact on QoS. By applying a unique perspective to these problems, our model is used to set a roadmap for future mobile IPv6 testbed construction.

Telebation: next-generation telemedicine in remote airway management using current wireless technologies.

PubMed

Mosier, Jarrod; Joseph, Bellal; Sakles, John C

2013-02-01

Since the first remote intubation with telemedicine guidance, wireless technology has advanced to enable more portable methods of telemedicine involvement in remote airway management. Three voice over Internet protocol (VoIP) services were evaluated for quality of image transmitted, data lag, and audio quality with remotely observed and assisted intubations in an academic emergency department. The VoIP clients evaluated were Apple (Cupertino, CA) FaceTime(®), Skype™ (a division of Microsoft, Luxembourg City, Luxembourg), and Tango(®) (TangoMe, Palo Alto, CA). Each client was tested over a Wi-Fi network as well as cellular third generation (3G) (Skype and Tango). All three VoIP clients provided acceptable image and audio quality. There is a significant data lag in image transmission and quality when VoIP clients are used over cellular broadband (3G) compared with Wi-Fi. Portable remote telemedicine guidance is possible with newer technology devices such as a smartphone or tablet, as well as VoIP clients used over Wi-Fi or cellular broadband.

The Deployment of IPv6 in an IPv4 World and Transition Strategies.

ERIC Educational Resources Information Center

Bouras, C.; Ganos, P.; Karaliotas, A.

2003-01-01

The current version of the IP protocol, IPv4, is the most widely used protocol in computer networks. This article describes mechanisms that can be used to facilitate the transition to the new version of the IP protocol, IPv6, and examines usability, usefulness and manageability. Describes how some of these mechanisms were applied to the Greek…

Repliscan: a tool for classifying replication timing regions.

PubMed

Zynda, Gregory J; Song, Jawon; Concia, Lorenzo; Wear, Emily E; Hanley-Bowdoin, Linda; Thompson, William F; Vaughn, Matthew W

2017-08-07

Replication timing experiments that use label incorporation and high throughput sequencing produce peaked data similar to ChIP-Seq experiments. However, the differences in experimental design, coverage density, and possible results make traditional ChIP-Seq analysis methods inappropriate for use with replication timing. To accurately detect and classify regions of replication across the genome, we present Repliscan. Repliscan robustly normalizes, automatically removes outlying and uninformative data points, and classifies Repli-seq signals into discrete combinations of replication signatures. The quality control steps and self-fitting methods make Repliscan generally applicable and more robust than previous methods that classify regions based on thresholds. Repliscan is simple and effective to use on organisms with different genome sizes. Even with analysis window sizes as small as 1 kilobase, reliable profiles can be generated with as little as 2.4x coverage.

Interplanetary Scintillation studies with the Murchison Wide-field Array III: Comparison of source counts and densities for radio sources and their sub-arcsecond components at 162 MHz

NASA Astrophysics Data System (ADS)

Chhetri, R.; Ekers, R. D.; Morgan, J.; Macquart, J.-P.; Franzen, T. M. O.

2018-06-01

We use Murchison Widefield Array observations of interplanetary scintillation (IPS) to determine the source counts of point (<0.3 arcsecond extent) sources and of all sources with some subarcsecond structure, at 162 MHz. We have developed the methodology to derive these counts directly from the IPS observables, while taking into account changes in sensitivity across the survey area. The counts of sources with compact structure follow the behaviour of the dominant source population above ˜3 Jy but below this they show Euclidean behaviour. We compare our counts to those predicted by simulations and find a good agreement for our counts of sources with compact structure, but significant disagreement for point source counts. Using low radio frequency SEDs from the GLEAM survey, we classify point sources as Compact Steep-Spectrum (CSS), flat spectrum, or peaked. If we consider the CSS sources to be the more evolved counterparts of the peaked sources, the two categories combined comprise approximately 80% of the point source population. We calculate densities of potential calibrators brighter than 0.4 Jy at low frequencies and find 0.2 sources per square degrees for point sources, rising to 0.7 sources per square degree if sources with more complex arcsecond structure are included. We extrapolate to estimate 4.6 sources per square degrees at 0.04 Jy. We find that a peaked spectrum is an excellent predictor for compactness at low frequencies, increasing the number of good calibrators by a factor of three compared to the usual flat spectrum criterion.

TRIC: an automated alignment strategy for reproducible protein quantification in targeted proteomics

PubMed Central

Röst, Hannes L.; Liu, Yansheng; D’Agostino, Giuseppe; Zanella, Matteo; Navarro, Pedro; Rosenberger, George; Collins, Ben C.; Gillet, Ludovic; Testa, Giuseppe; Malmström, Lars; Aebersold, Ruedi

2016-01-01

Large scale, quantitative proteomic studies have become essential for the analysis of clinical cohorts, large perturbation experiments and systems biology studies. While next-generation mass spectrometric techniques such as SWATH-MS have substantially increased throughput and reproducibility, ensuring consistent quantification of thousands of peptide analytes across multiple LC-MS/MS runs remains a challenging and laborious manual process. To produce highly consistent and quantitatively accurate proteomics data matrices in an automated fashion, we have developed the TRIC software which utilizes fragment ion data to perform cross-run alignment, consistent peak-picking and quantification for high throughput targeted proteomics. TRIC uses a graph-based alignment strategy based on non-linear retention time correction to integrate peak elution information from all LC-MS/MS runs acquired in a study. When compared to state-of-the-art SWATH-MS data analysis, the algorithm was able to reduce the identification error by more than 3-fold at constant recall, while correcting for highly non-linear chromatographic effects. On a pulsed-SILAC experiment performed on human induced pluripotent stem (iPS) cells, TRIC was able to automatically align and quantify thousands of light and heavy isotopic peak groups and substantially increased the quantitative completeness and biological information in the data, providing insights into protein dynamics of iPS cells. Overall, this study demonstrates the importance of consistent quantification in highly challenging experimental setups, and proposes an algorithm to automate this task, constituting the last missing piece in a pipeline for automated analysis of massively parallel targeted proteomics datasets. PMID:27479329

Somatodendritic surface expression of epitope-tagged and KChIP binding-deficient Kv4.2 channels in hippocampal neurons.

PubMed

Prechtel, Helena; Hartmann, Sven; Minge, Daniel; Bähring, Robert

2018-01-01

Kv4.2 channels mediate a subthreshold-activating somatodendritic A-type current (ISA) in hippocampal neurons. We examined the role of accessory Kv channel interacting protein (KChIP) binding in somatodendritic surface expression and activity-dependent decrease in the availability of Kv4.2 channels. For this purpose we transfected cultured hippocampal neurons with cDNA coding for Kv4.2 wild-type (wt) or KChIP binding-deficient Kv4.2 mutants. All channels were equipped with an externally accessible hemagglutinin (HA)-tag and an EGFP-tag, which was attached to the C-terminal end. Combined analyses of EGFP self-fluorescence, surface HA immunostaining and patch-clamp recordings demonstrated similar dendritic trafficking and functional surface expression for Kv4.2[wt]HA,EGFP and the KChIP binding-deficient Kv4.2[A14K]HA,EGFP. Coexpression of exogenous KChIP2 augmented the surface expression of Kv4.2[wt]HA,EGFP but not Kv4.2[A14K]HA,EGFP. Notably, activity-dependent decrease in availability was more pronounced in Kv4.2[wt]HA,EGFP + KChIP2 coexpressing than in Kv4.2[A14K]HA,EGFP + KChIP2 coexpressing neurons. Our results do not support the notion that accessory KChIP binding is a prerequisite for dendritic trafficking and functional surface expression of Kv4.2 channels, however, accessory KChIP binding may play a potential role in Kv4.2 modulation during intrinsic plasticity processes.

The antiproliferative cytostatic effects of a self-activating viridin prodrug

PubMed Central

Smith, Adam; Blois, Joseph; Yuan, Hushan; Aikawa, Elena; Ellson, Christian; Figueiredo, Jose-Luiz; Weissleder, Ralph; Kohler, Rainer; Yaffe, Michael B.; Cantley, Lewis C.; Josephson, Lee

2009-01-01

Although viridins like wortmannin (Wm) have long been examined as anticancer agents, their ability to self-activate has only recently been recognized. Here, we describe the cytostatic effects of a self-activating viridin (SAV), which is an inactive, polymeric prodrug. SAV self-activates to generate a bioactive, fluorescent viridin NBD-Wm with a half-time of 9.2 hours. With cultured A549 cells, 10 µmol/L SAV caused growth arrest without inducing apoptosis or cell death, a cytostatic action markedly different from other chemotherapeutic agents (vinblastine, camptothecin, and paclitaxel). In vivo, a SAV dosing of 1 mg/kg once in 48 hours (i.p.) resulted in growth arrest of an A549 tumor xenograft, with growth resuming when dosing ceased. With a peak serum concentration of SAV of 2.36 µmol/L (at 2 hours post i.p. injection), the concentration of bioactive NBD-Wm was 41 nmol/L based on the partial inhibition of neutrophil respiratory burst. Therefore, SAV was present as an inactive prodrug in serum (peak = 2.36 µmol/L), which generated low concentrations of active viridin (41 nmol/L). SAV is a prodrug, the slowrelease and cytostatic activities of which suggest that it might be useful as a component of metronomic-based chemotherapeutic strategies. PMID:19509266

Evidence for Holocene centennial variability in sea ice cover based on IP25 biomarker reconstruction in the southern Kara Sea (Arctic Ocean)

NASA Astrophysics Data System (ADS)

Hörner, Tanja; Stein, Rüdiger; Fahl, Kirsten

2017-10-01

The Holocene is characterized by the late Holocene cooling trend as well as by internal short-term centennial fluctuations. Because Arctic sea ice acts as a significant component (amplifier) within the climate system, investigating its past long- and short-term variability and controlling processes is beneficial for future climate predictions. This study presents the first biomarker-based (IP25 and PIP25) sea ice reconstruction from the Kara Sea (core BP00-07/7), covering the last 8 ka. These biomarker proxies reflect conspicuous short-term sea ice variability during the last 6.5 ka that is identified unprecedentedly in the source region of Arctic sea ice by means of a direct sea ice indicator. Prominent peaks of extensive sea ice cover occurred at 3, 2, 1.3 and 0.3 ka. Spectral analysis of the IP25 record revealed 400- and 950-year cycles. These periodicities may be related to the Arctic/North Atlantic Oscillation, but probably also to internal climate system fluctuations. This demonstrates that sea ice belongs to a complex system that more likely depends on multiple internal forcing.

Purification of nanogram-range immunoprecipitated DNA in ChIP-seq application.

PubMed

Zhong, Jian; Ye, Zhenqing; Lenz, Samuel W; Clark, Chad R; Bharucha, Adil; Farrugia, Gianrico; Robertson, Keith D; Zhang, Zhiguo; Ordog, Tamas; Lee, Jeong-Heon

2017-12-21

Chromatin immunoprecipitation-sequencing (ChIP-seq) is a widely used epigenetic approach for investigating genome-wide protein-DNA interactions in cells and tissues. The approach has been relatively well established but several key steps still require further improvement. As a part of the procedure, immnoprecipitated DNA must undergo purification and library preparation for subsequent high-throughput sequencing. Current ChIP protocols typically yield nanogram quantities of immunoprecipitated DNA mainly depending on the target of interest and starting chromatin input amount. However, little information exists on the performance of reagents used for the purification of such minute amounts of immunoprecipitated DNA in ChIP elution buffer and their effects on ChIP-seq data. Here, we compared DNA recovery, library preparation efficiency, and ChIP-seq results obtained with several commercial DNA purification reagents applied to 1 ng ChIP DNA and also investigated the impact of conditions under which ChIP DNA is stored. We compared DNA recovery of ten commercial DNA purification reagents and phenol/chloroform extraction from 1 to 50 ng of immunopreciptated DNA in ChIP elution buffer. The recovery yield was significantly different with 1 ng of DNA while similar in higher DNA amounts. We also observed that the low nanogram range of purified DNA is prone to loss during storage depending on the type of polypropylene tube used. The immunoprecipitated DNA equivalent to 1 ng of purified DNA was subject to DNA purification and library preparation to evaluate the performance of four better performing purification reagents in ChIP-seq applications. Quantification of library DNAs indicated the selected purification kits have a negligible impact on the efficiency of library preparation. The resulting ChIP-seq data were comparable with the dataset generated by ENCODE consortium and were highly correlated between the data from different purification reagents. This study provides comparative data on commercial DNA purification reagents applied to nanogram-range immunopreciptated ChIP DNA and evidence for the importance of storage conditions of low nanogram-range purified DNA. We verified consistent high performance of a subset of the tested reagents. These results will facilitate the improvement of ChIP-seq methodology for low-input applications.

[Progress and application prospect of pig induced pluripotent stem cells].

PubMed

Yan, Yi-Bo; Zhang, Yan-Li; Qi, Wei-Wei; Wan, Yong-Jie; Fan, Yi-Xuan; Wang, Feng

2011-04-01

Pig has always been the focus of establishing a big ungulate animal ES cell lines because of its convenient source, genetic similarity with humans, and their importance in animal husbandry, but little development is achieved. Induced pluripotent stem cells technology creates a new method of reprogramming somatic cells to pluripotent state. As the pig iPS cells is established and perfected, pig ES cells will be established in the coming years. The pig iPS cells will give a hint on other livestock ES cells. On the other hand, pig iPS cells can be used to improve the efficiency of transgenic cloning pigs to conduct effective breeding and conservation of breeds. It is particularly important that the pig iPS cells can provide new model for human medical research, a new donor cells for human tissue and organ engineering, and have extensive and far-reaching impact on the biomedical field. Here, we briefly review the major progress of iPS cells, and emphasize current state of pig iPS cells and its application prospect in biomedicine and animal husbandry in order to provide a useful reference for researchers working in this area.

Using OpenSSH to secure mobile LAN network traffic

NASA Astrophysics Data System (ADS)

Luu, Brian B.; Gopaul, Richard D.

2002-08-01

Mobile Internet Protocol (IP) Local Area Network (LAN) is a technique, developed by the U.S. Army Research Laboratory, which allows a LAN to be IP mobile when attaching to a foreign IP-based network and using this network as a means to retain connectivity to its home network. In this paper, we describe a technique that uses Open Secure Shell (OpenSSH) software to ensure secure, encrypted transmission of a mobile LAN's network traffic. Whenever a mobile LAN, implemented with Mobile IP LAN, moves to a foreign network, its gateway (router) obtains an IP address from the new network. IP tunnels, using IP encapsulation, are then established from the gateway through the foreign network to a home agent on its home network. These tunnels provide a virtual two-way connection to the home network for the mobile LAN as if the LAN were connected directly to its home network. Hence, when IP mobile, a mobile LAN's tunneled network traffic must traverse one or more foreign networks that may not be trusted. This traffic could be subject to eavesdropping, interception, modification, or redirection by malicious nodes in these foreign networks. To protect network traffic passing through the tunnels, OpenSSH is used as a means of encryption because it prevents surveillance, modification, and redirection of mobile LAN traffic passing across foreign networks. Since the software is found in the public domain, is available for most current operating systems, and is commonly used to provide secure network communications, OpenSSH is the software of choice.

Solar energetic particle events in different types of solar wind

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kahler, S. W.; Vourlidas, A., E-mail: stephen.kahler@kirtland.af.mil

2014-08-10

We examine statistically some properties of 96 20 MeV gradual solar energetic proton (SEP) events as a function of three different types of solar wind (SW) as classified by Richardson and Cane. Gradual SEP (E > 10 MeV) events are produced in shocks driven by fast (V ≳ 900 km s{sup –1}) and wide (W > 60°) coronal mass ejections (CMEs). We find no differences among the transient, fast, and slow SW streams for SEP 20 MeV proton event timescales. It has recently been found that the peak intensities Ip of these SEP events scale with the ∼2 MeV protonmore » background intensities, which may be a proxy for the near-Sun shock seed particles. Both the intensities Ip and their 2 MeV backgrounds are significantly enhanced in transient SW compared to those of fast and slow SW streams, and the values of Ip normalized to the 2 MeV backgrounds only weakly correlate with CME V for all SW types. This result implies that forecasts of SEP events could be improved by monitoring both the Sun and the local SW stream properties and that the well known power-law size distributions of Ip may differ between transient and long-lived SW streams. We interpret an observed correlation between CME V and the 2 MeV background for SEP events in transient SW as a manifestation of enhanced solar activity.« less

Marmoset induced pluripotent stem cells: Robust neural differentiation following pretreatment with dimethyl sulfoxide.

PubMed

Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L; Guerra, Bernadette; Lanford, Robert E; Hornsby, Peter J

2015-07-01

The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS) cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05-2% dimethyl sulfoxide (DMSO) for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy. Copyright © 2015. Published by Elsevier B.V.

Violence-related Versus Terror-related Stabbings: Significant Differences in Injury Characteristics.

PubMed

Rozenfeld, Michael; Givon, Adi; Peleg, Kobi

2018-05-01

To demonstrate the gap between injury epidemiology of terror-related stabbings (TRS) and non-terror-related intentional stabbings. Terror attacks with sharp instruments have multiplied recently, with many victims of these incidents presented to hospitals with penetrating injuries. Because most practical experience of surgeons with intentional stabbing injuries comes from treating victims of interpersonal violence, potential gaps in knowledge may exist if injuries from TRS significantly differ from interpersonal stabbings (IPS). A retrospective study of 1615 patients from intentional stabbing events recorded in the Israeli National Trauma Registry during the period of "Knife Intifada" (January 2013-March 2016). All stabbings were divided into TRS and IPS. The 2 categories were compared in terms of sustained injuries, utilization of hospital resources, and clinical outcomes. TRS patients were older, comprised more females and were ethnically homogenous. Most IPS incidents happened on weekdays and at night hours, whereas TRS events peaked midweek during morning and afternoon hours. TRS patients had more injuries of head, face, and neck, and severe head and neck injuries. IPS patients had more abdomen injuries; however, respective injuries in the TRS group were more severe. Greater injury severity of the TRS patients reflected on their higher hospital resources utilization and greater in-hospital mortality. Victims of terror stabbings are profoundly different in their characteristics, sustain injuries of a different profile and greater severity, require more hospital resources, and have worse off clinical outcomes, emphasizing the need of the healthcare systems to adjust itself appropriately to deal successfully with future terror attacks.

SraTailor: graphical user interface software for processing and visualizing ChIP-seq data.

PubMed

Oki, Shinya; Maehara, Kazumitsu; Ohkawa, Yasuyuki; Meno, Chikara

2014-12-01

Raw data from ChIP-seq (chromatin immunoprecipitation combined with massively parallel DNA sequencing) experiments are deposited in public databases as SRAs (Sequence Read Archives) that are publically available to all researchers. However, to graphically visualize ChIP-seq data of interest, the corresponding SRAs must be downloaded and converted into BigWig format, a process that involves complicated command-line processing. This task requires users to possess skill with script languages and sequence data processing, a requirement that prevents a wide range of biologists from exploiting SRAs. To address these challenges, we developed SraTailor, a GUI (Graphical User Interface) software package that automatically converts an SRA into a BigWig-formatted file. Simplicity of use is one of the most notable features of SraTailor: entering an accession number of an SRA and clicking the mouse are the only steps required to obtain BigWig-formatted files and to graphically visualize the extents of reads at given loci. SraTailor is also able to make peak calls, generate files of other formats, process users' own data, and accept various command-line-like options. Therefore, this software makes ChIP-seq data fully exploitable by a wide range of biologists. SraTailor is freely available at http://www.devbio.med.kyushu-u.ac.jp/sra_tailor/, and runs on both Mac and Windows machines. © 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model.

PubMed

Mirzaei, Hamed; Salehi, Hossein; Oskuee, Reza Kazemi; Mohammadpour, Ali; Mirzaei, Hamid Reza; Sharifi, Mohammad Reza; Salarinia, Reza; Darani, Hossein Yousofi; Mokhtari, Mojgan; Masoudifar, Aria; Sahebkar, Amirhossein; Salehi, Rasoul; Jaafari, Mahmoud Reza

2018-04-10

Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of fully non-inductive plasmas heated by medium and high-harmonic fast waves in the national spherical torus experiment upgrade

NASA Astrophysics Data System (ADS)

Taylor, G.; Poli, F.; Bertelli, N.; Harvey, R. W.; Hosea, J. C.; Mueller, D.; Perkins, R. J.; Phillips, C. K.; Raman, R.

2015-12-01

A major challenge for spherical tokamak development is to start-up and ramp-up the plasma current (Ip) without using a central solenoid. Experiments in the National Spherical Torus eXperiment (NSTX) demonstrated that 1.4 MW of 30 MHz high-harmonic fast wave (HHFW) power could generate an Ip = 300 kA H-mode discharge with a non-inductive Ip fraction, fNI ˜ 0.7. The discharge had an axial toroidal magnetic field (BT(0)) of 0.55 T, the maximum BT(0) available on NSTX. NSTX has undergone a major upgrade (NSTX-U), that will eventually allow the generation of BT(0) ≤ 1 T and Ip ≤ 2 MA plasmas. Full wave simulations of 30 MHz HHFW and medium harmonic fast wave (MHFW) heating in NSTX-U predict significantly reduced FW power loss in the plasma edge at the higher BT(0) achievable in NSTX-U. HHFW experiments will aim to generate stable, fNI ˜ 1, Ip = 300 kA H-mode plasmas and to ramp Ip from 250 to 400 kA with FW power. Time-dependent TRANSP simulations are used to develop non-inductive Ip ramp-up and sustainment using 30 MHz FW power. This paper presents results from these RF simulations and plans for developing non-inductive plasmas heated by FW power.

Induced Pluripotent Stem (iPS) Cells in Dentistry: A Review

PubMed Central

Malhotra, Neeraj

2016-01-01

iPS cells are derived from somatic cells via transduction and expression of selective transcription factors. Both viral-integrating (like retroviral) and non-integrating (like, mRNA or protein-based) techniques are available for the production of iPS cells. In the field of dentistry, iPS cells have been derived from stem cells of apical papilla, dental pulp stem cells, and stem cells from exfoliated deciduous teeth, gingival and periodontal ligament fibroblasts, and buccal mucosa fibroblasts. iPS cells have the potential to differentiate into all derivatives of the 3 primary germ layers i.e. ectoderm, endoderm, and mesoderm. They are autogeneically accessible, and can produce patient-specific or disease-specific cell lines without the issue of ethical controversy. They have been successfully tested to produce mesenchymal stem cells-like cells, neural crest-like cells, ameloblasts-like cells, odontoblasts-like cells, and osteoprogenitor cells. These cells can aid in regeneration of periodontal ligament, alveolar bone, cementum, dentin-pulp complex, as well as possible Biotooth formation. However certain key issues like, epigenetic memory of iPS cells, viral-transduction, tumorgenesis and teratoma formation need to be overcome, before they can be successfully used in clinical practice. The article discusses the sources, pros and cons, and current applications of iPS cells in dentistry with an emphasis on encountered challenges and their solutions. PMID:27572712

Advancing High Current Startup via Localized Helicity Injection in the PEGASUS Toroidal Experiment

NASA Astrophysics Data System (ADS)

Hinson, E. T.; Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Perry, J. M.; Redd, A. J.; Schlossberg, D. J.

2013-10-01

Non-solenoidal startup via local helicity injection (LHI) and poloidal field induction is used to produce Ip = 0 . 17 MA tokamak discharges. Impurity contamination has been reduced to negligible levels by use of conical frustum cathode geometry and local scraper limiters. Attainable currents are governed by global limits of helicity and energy balance, and Taylor relaxation. A simple lumped parameter model based on these limits is used to project discharge evolution, and indicates that attaining 1 MA in NSTX-U will require LHI-driven effective loop voltages to dominate contributions from dLp / dt . This regime contrasts with results to date and will be tested at 0.3 MA in PEGASUS with a new integrated multi-injector array. Injector impedance characteristics are consistent with magnetically-limited regimes observed in higher-power foilless diodes. Bursts of MHD are measured on time scales of order ~ 100 μ s, and correlate with rapid equilibrium changes, discrete rises in Ip, redistribution of the toroidal current, ion heating (Ti ~ 1 keV), transient drops in injector voltage, and apparent n = 1 line-tied kink activity at the injector. NIMROD simulations of high-field-side HI discharges in PEGASUS are in qualitative agreement, suggesting Ip buildup results from inward propagating toroidal current loops created by intermittent reconnection of injected current streams. Work supported by US DOE Grant DE-FG02-96ER54375.

Characterization and on-sky demonstration of an integrated photonic spectrograph for astronomy.

PubMed

Cvetojevic, N; Lawrence, J S; Ellis, S C; Bland-Hawthorn, J; Haynes, R; Horton, A

2009-10-12

We present results from the first on-sky demonstration of a prototype astronomical integrated photonic spectrograph (IPS) using the Anglo-Australian Telescope near-infrared imaging spectrometer (IRIS2) at Siding Spring Observatory to observe atmospheric molecular OH emission lines. We have succeeded in detecting upwards of 27 lines, and demonstrated the practicality of the IPS device for astronomy. Furthermore, we present a laboratory characterization of the device, which is a modified version of a commercial arrayed-waveguide grating multiplexer. We measure the spectral resolution full-width-half-maximum to be 0.75 +/- 0.05 nm (giving R = lambda/deltalambda = 2100 +/- 150 at 1500 nm). We find the free spectral range to be 57.4 +/- 0.6 nm and the peak total efficiency to be approximately 65%. Finally, we briefly discuss the future steps required to realize an astronomical instrument based on this technology concept.

Multireference configuration interaction calculations of the first six ionization potentials of the uranium atom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bross, David H.; Parmar, Payal; Peterson, Kirk A., E-mail: kipeters@wsu.edu

The first 6 ionization potentials (IPs) of the uranium atom have been calculated using multireference configuration interaction (MRCI+Q) with extrapolations to the complete basis set limit using new all-electron correlation consistent basis sets. The latter was carried out with the third-order Douglas-Kroll-Hess Hamiltonian. Correlation down through the 5s5p5d electrons has been taken into account, as well as contributions to the IPs due to the Lamb shift. Spin-orbit coupling contributions calculated at the 4-component Kramers restricted configuration interaction level, as well as the Gaunt term computed at the Dirac-Hartree-Fock level, were added to the best scalar relativistic results. The final ionizationmore » potentials are expected to be accurate to at least 5 kcal/mol (0.2 eV) and thus more reliable than the current experimental values of IP{sub 3} through IP{sub 6}.« less

Doubling the spectrum of time-domain induced polarization by harmonic de-noising, drift correction, spike removal, tapered gating and data uncertainty estimation

NASA Astrophysics Data System (ADS)

Olsson, Per-Ivar; Fiandaca, Gianluca; Larsen, Jakob Juul; Dahlin, Torleif; Auken, Esben

2016-11-01

The extraction of spectral information in the inversion process of time-domain (TD) induced polarization (IP) data is changing the use of the TDIP method. Data interpretation is evolving from a qualitative description of the subsurface, able only to discriminate the presence of contrasts in chargeability parameters, towards a quantitative analysis of the investigated media, which allows for detailed soil- and rock-type characterization. Two major limitations restrict the extraction of the spectral information of TDIP data in the field: (i) the difficulty of acquiring reliable early-time measurements in the millisecond range and (ii) the self-potential background drift in the measured potentials distorting the shape of the late-time IP responses, in the second range. Recent developments in TDIP acquisition equipment have given access to full-waveform recordings of measured potentials and transmitted current, opening for a breakthrough in data processing. For measuring at early times, we developed a new method for removing the significant noise from power lines contained in the data through a model-based approach, localizing the fundamental frequency of the power-line signal in the full-waveform IP recordings. By this, we cancel both the fundamental signal and its harmonics. Furthermore, an efficient processing scheme for identifying and removing spikes in TDIP data was developed. The noise cancellation and the de-spiking allow the use of earlier and narrower gates, down to a few milliseconds after the current turn-off. In addition, tapered windows are used in the final gating of IP data, allowing the use of wider and overlapping gates for higher noise suppression with minimal distortion of the signal. For measuring at late times, we have developed an algorithm for removal of the self-potential drift. Usually constant or linear drift-removal algorithms are used, but these algorithms often fail in removing the background potentials present when the electrodes used for potential readings are previously used for current injection, also for simple contact resistance measurements. We developed a drift-removal scheme that models the polarization effect and efficiently allows for preserving the shape of the IP responses at late times. Uncertainty estimates are essential in the inversion of IP data. Therefore, in the final step of the data processing, we estimate the data standard deviation based on the data variability within the IP gates and the misfit of the background drift removal Overall, the removal of harmonic noise, spikes, self-potential drift, tapered windowing and the uncertainty estimation allows for doubling the usable range of TDIP data to almost four decades in time (corresponding to four decades in frequency), which will significantly advance the applicability of the IP method.

Linear Collider Test Facility: Twiss Parameter Analysis at the IP/Post-IP Location of the ATF2 Beam Line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolzon, Benoit; /Annecy, LAPP; Jeremie, Andrea

2012-07-02

At the first stage of the ATF2 beam tuning, vertical beam size is usually bigger than 3 {micro}m at the IP. Beam waist measurements using wire scanners and a laser wire are usually performed to check the initial matching of the beam through to the IP. These measurements are described in this paper for the optics currently used ({beta}{sub x} = 4cm and {beta}{sub y} = 1mm). Software implemented in the control room to automate these measurements with integrated analysis is also described. Measurements showed that {beta} functions and emittances were within errors of measurements when no rematching and couplingmore » corrections were done. However, it was observed that the waist in the horizontal (X) and vertical (Y) plane was abnormally shifted and simulations were performed to try to understand these shifts. They also showed that multiknobs are needed in the current optics to correct simultaneously {alpha}{sub x}, {alpha}{sub y} and the horizontal dispersion (D{sub x}). Such multiknobs were found and their linearity and orthogonality were successfully checked using MAD optics code. The software for these multiknobs was implemented in the control room and waist scan measurements using the {alpha}{sub y} knob were successfully performed.« less

Staffing and structure of infection prevention and control programs.

PubMed

Stone, Patricia W; Dick, Andrew; Pogorzelska, Monika; Horan, Teresa C; Furuya, E Yoko; Larson, Elaine

2009-06-01

The nature of infection prevention and control is changing; however, little is known about current staffing and structure of infection prevention and control programs. Our objectives were to provide a snapshot of the staffing and structure of hospital-based infection prevention and control programs in the United States. A Web-based survey was sent to 441 hospitals that participate in the National Healthcare Safety Network. The response rate was 66% (n = 289); data were examined on 821 professionals. Infection preventionist (IP) staffing was significantly negatively related to bed size, with higher staffing in smaller hospitals (P < .001). Median staffing was 1 IP per 167 beds. Forty-seven percent of IPs were certified, and 24 percent had less than 2 years of experience. Most directors or hospital epidemiologists were reported to have authority to close beds for outbreaks always or most of the time (n = 225, 78%). Only 32% (n = 92) reported using an electronic surveillance system to track infections. This study is the first to provide a comprehensive description of current infection prevention and control staffing, organization, and support in a select group of hospitals across the nation. Further research is needed to identify effective staffing levels for various hospital types as well as examine how the IP role is changing over time.

Staffing and structure of infection prevention and control programs

PubMed Central

Stone, Patricia W.; Dick, Andrew; Pogorzelska, Monika; Horan, Teresa C.; Furuya, E. Yoko; Larson, Elaine

2009-01-01

Background The nature of infection prevention and control is changing; however, little is known about current staffing and structure of infection prevention and control programs. Methods Our objectives were to provide a snapshot of the staffing and structure of hospital-based infection prevention and control programs in the United States. A Web-based survey was sent to 441 hospitals that participate in the National Healthcare Safety Network. Results The response rate was 66% (n = 289); data were examined on 821 professionals. Infection preventionist (IP) staffing was significantly negatively related to bed size, with higher staffing in smaller hospitals (P < .001). Median staffing was 1 IP per 167 beds. Forty-seven percent of IPs were certified, and 24 percent had less than 2 years of experience. Most directors or hospital epidemiologists were reported to have authority to close beds for outbreaks always or most of the time (n = 225, 78%). Only 32% (n = 92) reported using an electronic surveillance system to track infections. Conclusion This study is the first to provide a comprehensive description of current infection prevention and control staffing, organization, and support in a select group of hospitals across the nation. Further research is needed to identify effective staffing levels for various hospital types as well as examine how the IP role is changing over time. PMID:19201510

Two-year clinical evaluation of IPS Empress II ceramic onlays/inlays.

PubMed

Tagtekin, D A; Ozyöney, G; Yanikoglu, F

2009-01-01

The stronger the ceramic material, the longer the restoration stays in the mouth. The current study evaluated the two-year clinical performance of a strong ceramic system, IPS Empress II, with increased strength on onlay/inlay restorations of molars. Teeth from 35 patients, including three premolars and 32 molars, were prepared for 28 onlay and seven inlay restorations with IPS Empress II ceramics. The restorations were cemented with a highly viscous, dual-curing luting composite cement (Bifix) and evaluated by two examiners using USPHS criteria at baseline (one week following insertion), six months, one year and two years. The baseline scores and recalls were assessed by Wilcoxon signed rank test. Statistically significant marginal discoloration at the Bravo level was found at the 12- and 24-month recalls (p=0.046). One debonding was statistically insignificant. No changes were observed with respect to anamnesis, such as any symptom from the TMJ or masticatory muscles. No restorations were replaced due to hypersensitivity or were missing at the two-year evaluation. Any wear on the restoration, antagonist tooth or any changes of proximal contacts were not observed. IPS Empress II Ceramics were found to be appropriate as onlay/inlay restorations for clinical use under the conditions of the current study.

Dental anomalies in 14 patients with IP: clinical and radiological analysis and review.

PubMed

Santa-Maria, Fernanda D; Mariath, Luiza Monteavaro; Poziomczyk, Cláudia S; Maahs, Marcia A P; Rosa, Rafael F M; Zen, Paulo R G; Schüller-Faccini, Lavínia; Kiszewski, Ana Elisa

2017-06-01

Current knowledge on dental anomalies in patients with incontinentia pigmenti (IP) has been obtained by examining case reports; however, an overall characterization of such alterations remains lacking. The objective of this study was to determine the frequency, type and location of dental alterations in IP using a case series. Fourteen patients (9 children and 5 adults) with a clinical diagnosis of IP who presented dental anomalies were included in this study. All patients were administered a clinical questionnaire, dental examination and radiological investigation. In the present case series, agenesis of primary dentition was present in 60 % of patients and agenesis of permanent tooth was present in 92.8 % of patients. Most cases were missing at least 6 teeth. Second molar agenesis was present in 13 patients (92.8 %). Anomalies in dental crowns occurred in 71.4 % of cases, and the central incisor was most frequently affected. Two adult patients still had primary teeth. Malocclusion was found in 10 patients (71.4 %). High-arched palate was observed in 7 (50 %) patients. Patients with IP present alterations in both primary and permanent dentition. Because the agenesis of permanent teeth is more common, primary teeth are not always replaced. In addition, the durability of primary dentition appears to be greater in IP. This study shows that patients with IP experience significant loss of teeth, especially in permanent dentition, and have an increased risk of high-arched palate compared to the general population. Prophylactic care of primary teeth in IP is relevant for improving functional and aesthetic outcomes until dental prostheses are implanted.

Treatment of Diabetes Mellitus Using iPS Cells and Spice Polyphenols

PubMed Central

Chen, Liang

2017-01-01

Diabetes mellitus is a chronic disease that threatens human health. The disease is caused by a metabolic disorder of the endocrine system, and long-term illness can lead to tissue and organ damage to the cardiovascular, endocrine, nervous, and urinary systems. Currently, the disease prevalence is 11.4%, the treatment rate is 48.2%, and the mortality rate is 2.7% worldwide. Comprehensive and effective control of diabetes, as well as the use of insulin, requires further study to develop additional treatment options. Here, we reviewed the current reprogramming of somatic cells using specific factors to induced pluripotent stem (iPS) cells capable of repairing islet β cell damage in diabetes patients to treat patients with type 1 diabetes mellitus. We also discuss the shortcomings associated with clinical use of iPS cells. Additionally, certain polyphenols found in spices might improve glucose homeostasis and insulin resistance in diabetes patients, thereby constituting promising options for the treatment of type 2 diabetes. PMID:28758131

Treatment of Diabetes Mellitus Using iPS Cells and Spice Polyphenols.

PubMed

Ge, Qi; Chen, Liang; Chen, Keping

2017-01-01

Diabetes mellitus is a chronic disease that threatens human health. The disease is caused by a metabolic disorder of the endocrine system, and long-term illness can lead to tissue and organ damage to the cardiovascular, endocrine, nervous, and urinary systems. Currently, the disease prevalence is 11.4%, the treatment rate is 48.2%, and the mortality rate is 2.7% worldwide. Comprehensive and effective control of diabetes, as well as the use of insulin, requires further study to develop additional treatment options. Here, we reviewed the current reprogramming of somatic cells using specific factors to induced pluripotent stem (iPS) cells capable of repairing islet β cell damage in diabetes patients to treat patients with type 1 diabetes mellitus. We also discuss the shortcomings associated with clinical use of iPS cells. Additionally, certain polyphenols found in spices might improve glucose homeostasis and insulin resistance in diabetes patients, thereby constituting promising options for the treatment of type 2 diabetes.

A study to evaluate STS heads-up ascent trajectory performance employing a minimum-Hamiltonian optimization strategy

NASA Technical Reports Server (NTRS)

Sinha, Sujit

1988-01-01

A study was conducted to evaluate the performance implications of a heads-up ascent flight design for the Space Transportation System, as compared to the current heads-down flight mode. The procedure involved the use of the Minimum Hamiltonian Ascent Shuttle Trajectory Evaluation Program, which is a three-degree-of-freedom moment balance simulation of shuttle ascent. A minimum-Hamiltonian optimization strategy was employed to maximize injection weight as a function of maximum dynamic pressure constraint and Solid Rocket Motor burnrate. Performance Reference Mission Four trajectory groundrules were used for consistency. The major conclusions are that for heads-up ascent and a mission nominal design maximum dynamic pressure value of 680 psf, the optimum solid motor burnrate is 0.394 ips, which produces a performance enhancement of 4293 lbm relative to the baseline heads-down ascent, with 0.368 ips burnrate solid motors and a 680 psf dynamic pressure constraint. However, no performance advantage exists for heads-up flight if the current Solid Rocket Motor target burnrate of 0.368 ips is used. The advantage of heads-up ascent flight employing the current burnrate is that Space Shuttle Main Engine throttling for dynamic pressure control is not necessary.

The incubation period of Buruli ulcer (Mycobacterium ulcerans infection).

PubMed

Trubiano, Jason A; Lavender, Caroline J; Fyfe, Janet A M; Bittmann, Simone; Johnson, Paul D R

2013-01-01

Buruli Ulcer (BU) is caused by the environmental microbe Mycobacterium ulcerans. Despite unclear transmission, contact with a BU endemic region is the key known risk factor. In Victoria, Australia, where endemic areas have been carefully mapped, we aimed to estimate the Incubation Period (IP) of BU by interviewing patients who reported defined periods of contact with an endemic area prior to BU diagnosis. A retrospective review was undertaken of 408 notifications of BU in Victoria from 2002 to 2012. Telephone interviews using a structured questionnaire and review of notification records were performed. Patients with a single visit exposure to a defined endemic area were included and the period from exposure to disease onset determined (IP). We identified 111 of 408 notified patients (27%) who had a residential address outside a known endemic area, of whom 23 (6%) reported a single visit exposure within the previous 24 months. The median age of included patients was 30 years (range: 6 to 73) and 65% were male. 61% had visited the Bellarine Peninsula, currently the most active endemic area. The median time from symptom onset to diagnosis was 71 days (range: 34-204 days). The midpoint of the reported IP range was utilized to calculate a point estimate of the IP for each case. Subsequently, the mean IP for the cohort was calculated at 135 days (IQR: 109-160; CI 95%: 113.9-156), corresponding to 4.5 months or 19.2 weeks. The shortest IP recorded was 32 days and longest 264 days (Figure 1 & 2). IP did not vary for variables investigated. The estimated mean IP of BU in Victoria is 135 days (IQR: 109-160 days), 4.5 months. The shortest recorded was IP 34 days and longest 264 days. A greater understanding of BU IP will aid clinical risk assessment and future research.

Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.

PubMed

Ostadhadi, Sattar; Khan, Muhammad Imran; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Jazaeri, Farahnaz; Zolfaghari, Samira; Dehpour, Ahmad-Reza

2016-04-01

Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30 mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75 mg/kg, i.p.), or l-arginine (750 mg/kg, i.p. NO precursor), or sildenafil (5mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10mg/kg, i.p, a non-specific NOS inhibitor), 7-nitoinidazol (30 mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05 mg/kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01 mg/kg) or L-NAME (1mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test. Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production. Copyright © 2016 Elsevier Inc. All rights reserved.

The auxiliary subunit KChIP2 is an essential regulator of homeostatic excitability.

PubMed

Wang, Hong-Gang; He, Xiao Ping; Li, Qiang; Madison, Roger D; Moore, Scott D; McNamara, James O; Pitt, Geoffrey S

2013-05-10

The necessity for, or redundancy of, distinctive KChIP proteins is not known. Deletion of KChIP2 leads to increased susceptibility to epilepsy and to a reduction in IA and increased excitability in pyramidal hippocampal neurons. KChIP2 is essential for homeostasis in hippocampal neurons. Mutations in K(A) channel auxiliary subunits may be loci for epilepsy. The somatodendritic IA (A-type) K(+) current underlies neuronal excitability, and loss of IA has been associated with the development of epilepsy. Whether any one of the four auxiliary potassium channel interacting proteins (KChIPs), KChIP1-KChIP4, in specific neuronal populations is critical for IA is not known. Here we show that KChIP2, which is abundantly expressed in hippocampal pyramidal cells, is essential for IA regulation in hippocampal neurons and that deletion of Kchip2 affects susceptibility to limbic seizures. The specific effects of Kchip2 deletion on IA recorded from isolated hippocampal pyramidal neurons were a reduction in amplitude and shift in the V½ for steady-state inactivation to hyperpolarized potentials when compared with WT neurons. Consistent with the relative loss of IA, hippocampal neurons from Kchip2(-/-) mice showed increased excitability. WT cultured neurons fired only occasional single action potentials, but the average spontaneous firing rate (spikes/s) was almost 10-fold greater in Kchip2(-/-) neurons. In slice preparations, spontaneous firing was detected in CA1 pyramidal neurons from Kchip2(-/-) mice but not from WT. Additionally, when seizures were induced by kindling, the number of stimulations required to evoke an initial class 4 or 5 seizure was decreased, and the average duration of electrographic seizures was longer in Kchip2(-/-) mice compared with WT controls. Together, these data demonstrate that the KChIP2 is essential for physiologic IA modulation and homeostatic stability and that there is a lack of functional redundancy among the different KChIPs in hippocampal neurons.

Adaptation technology between IP layer and optical layer in optical Internet

NASA Astrophysics Data System (ADS)

Ji, Yuefeng; Li, Hua; Sun, Yongmei

2001-10-01

Wavelength division multiplexing (WDM) optical network provides a platform with high bandwidth capacity and is supposed to be the backbone infrastructure supporting the next-generation high-speed multi-service networks (ATM, IP, etc.). In the foreseeable future, IP will be the predominant data traffic, to make fully use of the bandwidth of the WDM optical network, many attentions have been focused on IP over WDM, which has been proposed as the most promising technology for new kind of network, so-called Optical Internet. According to OSI model, IP is in the 3rd layer (network layer) and optical network is in the 1st layer (physical layer), so the key issue is what adaptation technology should be used in the 2nd layer (data link layer). In this paper, firstly, we analyze and compare the current adaptation technologies used in backbone network nowadays. Secondly, aiming at the drawbacks of above technologies, we present a novel adaptation protocol (DONA) between IP layer and optical layer in Optical Internet and describe it in details. Thirdly, the gigabit transmission adapter (GTA) we accomplished based on the novel protocol is described. Finally, we set up an experiment platform to apply and verify the DONA and GTA, the results and conclusions of the experiment are given.

Network Upgrade for the SLC: PEP II Network

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crane, M.; Call, M.; Clark, S.

2011-09-09

The PEP-II control system required a new network to support the system functions. This network, called CTLnet, is an FDDI/Ethernet based network using only TCP/IP protocols. An upgrade of the SLC Control System micro communications to use TCP/IP and SLCNET would allow all PEP-II control system nodes to use TCP/IP. CTLnet is private and separate from the SLAC public network. Access to nodes and control system functions is provided by multi-homed application servers with connections to both the private CTLnet and the SLAC public network. Monitoring and diagnostics are provided using a dedicated system. Future plans and current status informationmore » is included.« less

Improved i.p. drug delivery with bioadhesive nanoparticles

PubMed Central

Deng, Yang; Yang, Fan; Cocco, Emiliano; Song, Eric; Zhang, Junwei; Cui, Jiajia; Mohideen, Muneeb; Bellone, Stefania; Santin, Alessandro D.; Saltzman, W. Mark

2016-01-01

The i.p. administration of chemotherapy in ovarian and uterine serous carcinoma patients by biodegradable nanoparticles may represent a highly effective way to suppress peritoneal carcinomatosis. However, the efficacy of nanoparticles loaded with chemotherapeutic agents is currently hampered by their fast clearance by lymphatic drainage. Here, we show that a unique formulation of bioadhesive nanoparticles (BNPs) can interact with mesothelial cells in the abdominal cavity and significantly extend the retention of the nanoparticles in the peritoneal space. BNPs loaded with a potent chemotherapeutic agent [epothilone B (EB)] showed significantly lower systemic toxicity and higher therapeutic efficacy against i.p. chemotherapy-resistant uterine serous carcinoma-derived xenografts compared with free EB and non-BNPs loaded with EB. PMID:27663731

A fluid modeling perspective on the tokamak power scrape-off width using SOLPS-ITER

NASA Astrophysics Data System (ADS)

Meier, Eric

2016-10-01

SOLPS-ITER, a 2D fluid code, is used to conduct the first fluid modeling study of the physics behind the power scrape-off width (λq). When drift physics are activated in the code, λq is insensitive to changes in toroidal magnetic field (Bt), as predicted by the 0D heuristic drift (HD) model developed by Goldston. Using the HD model, which quantitatively agrees with regression analysis of a multi-tokamak database, λq in ITER is projected to be 1 mm instead of the previously assumed 4 mm, magnifying the challenge of maintaining the peak divertor target heat flux below the technological limit. These simulations, which use DIII-D H-mode experimental conditions as input, and reproduce the observed high-recycling, attached outer target plasma, allow insights into the scrape-off layer (SOL) physics that set λq. Independence of λq with respect to Bt suggests that SOLPS-ITER captures basic HD physics: the effect of Bt on the particle dwell time ( Bt) cancels with the effect on drift speed ( 1 /Bt), fixing the SOL plasma density width, and dictating λq. Scaling with plasma current (Ip), however, is much weaker than the roughly 1 /Ip dependence predicted by the HD model. Simulated net cross-separatrix particle flux due to magnetic drifts exceeds the anomalous particle transport, and a Pfirsch-Schluter-like SOL flow pattern is established. Up-down ion pressure asymmetry enables the net magnetic drift flux. Drifts establish in-out temperature asymmetry, and an associated thermoelectric current carries significant heat flux to the outer target. The density fall-off length in the SOL is similar to the electron temperature fall-off length, as observed experimentally. Finally, opportunities and challenges foreseen in ongoing work to extrapolate SOLPS-ITER and the HD model to ITER and future machines will be discussed. Supported by U.S. Department of Energy Contract DESC0010434.

Massive GGAAs in genomic repetitive sequences serve as a nuclear reservoir of NF-κB.

PubMed

Wu, Jian; Wang, Qiao; Dai, Wei; Wang, Wei; Yue, Ming; Wang, Jinke

2018-04-13

Nuclear factor κB (NF-κB) is a DNA-binding transcription factor. Characterizing its genomic binding sites is crucial for understanding its gene regulatory function and mechanism in cells. This study characterized the binding sites of NF-κB RelA/p65 in the tumor neurosis factor-α (TNFα) stimulated HeLa cells by a precise chromatin immunoprecipitation-sequencing (ChIP-seq). The results revealed that NF-κB binds nontraditional motifs (nt-motifs) containing conserved GGAA quadruplet. Moreover, nt-motifs mainly distribute in the peaks nearby centromeres that contain a larger number of repetitive elements such as satellite, simple repeats and short interspersed nuclear elements (SINEs). This intracellular binding pattern was then confirmed by the in vitro detection, indicating that NF-κB dimers can bind the nontraditional κB (nt-κB) sites with low affinity. However, this binding hardly activates transcription. This study thus deduced that NF-κB binding nt-motifs may realize functions other than gene regulation as NF-κB binding traditional motifs (t-motifs). To testify the deduction, many ChIP-seq data of other cell lines were then analyzed. The results indicate that NF-κB binding nt-motifs is also widely present in other cells. The ChIP-seq data analysis also revealed that nt-motifs more widely distribute in the peaks with low-fold enrichment. Importantly, it was also found that NF-κB binding nt-motifs is mainly present in the resting cells, whereas NF-κB binding t-motifs is mainly present in the stimulated cells. Astonishingly, no known function was enriched by the gene annotation of nt-motif peaks. Based on these results, this study proposed that the nt-κB sites that extensively distribute in larger numbers of repeat elements function as a nuclear reservoir of NF-κB. The nuclear NF-κB proteins stored at nt-κB sites in the resting cells may be recruited to the t-κB sites for regulating its target genes upon stimulation. Copyright © 2018 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

First report on an inotropic peptide activating tetrodotoxin-sensitive, "neuronal" sodium currents in the heart.

PubMed

Kirchhof, Paulus; Tal, Tzachy; Fabritz, Larissa; Klimas, Jan; Nesher, Nir; Schulte, Jan S; Ehling, Petra; Kanyshkova, Tatayana; Budde, Thomas; Nikol, Sigrid; Fortmueller, Lisa; Stallmeyer, Birgit; Müller, Frank U; Schulze-Bahr, Eric; Schmitz, Wilhelm; Zlotkin, Eliahu; Kirchhefer, Uwe

2015-01-01

New therapeutic approaches to improve cardiac contractility without severe risk would improve the management of acute heart failure. Increasing systolic sodium influx can increase cardiac contractility, but most sodium channel activators have proarrhythmic effects that limit their clinical use. Here, we report the cardiac effects of a novel positive inotropic peptide isolated from the toxin of the Black Judean scorpion that activates neuronal tetrodotoxin-sensitive sodium channels. All venoms and peptides were isolated from Black Judean Scorpions (Buthotus Hottentotta) caught in the Judean Desert. The full scorpion venom increased left ventricular function in sedated mice in vivo, prolonged ventricular repolarization, and provoked ventricular arrhythmias. An inotropic peptide (BjIP) isolated from the full venom by chromatography increased cardiac contractility but did neither provoke ventricular arrhythmias nor prolong cardiac repolarization. BjIP increased intracellular calcium in ventricular cardiomyocytes and prolonged inactivation of the cardiac sodium current. Low concentrations of tetrodotoxin (200 nmol/L) abolished the effect of BjIP on calcium transients and sodium current. BjIP did not alter the function of Nav1.5, but selectively activated the brain-type sodium channels Nav1.6 or Nav1.3 in cellular electrophysiological recordings obtained from rodent thalamic slices. Nav1.3 (SCN3A) mRNA was detected in human and mouse heart tissue. Our pilot experiments suggest that selective activation of tetrodotoxin-sensitive neuronal sodium channels can safely increase cardiac contractility. As such, the peptide described here may become a lead compound for a new class of positive inotropic agents. © 2014 American Heart Association, Inc.

Power Balance Modeling of Local Helicity Injection for Non-Solenoidal ST Startup

NASA Astrophysics Data System (ADS)

Weberski, J. D.; Barr, J. L.; Bongard, M. W.; Fonck, R. J.; Perry, J. M.; Reusch, J. A.

2017-10-01

A zero-dimensional power balance model for predicting Ip(t) for Local Helicity Injection (LHI) discharges has been used to interpret experimental results from recent experimental campaigns using high-field-side (HFS) helicity injection. This model quantifies LHI's effective drive (Veff) through helicity balance while enforcing the Taylor relaxation current limit and tracking inductive effects to determine Ip(t) . Recent analysis of HFS LHI discharges indicate LHI is the dominant source of drive and provides Veff up to 1.3 V while geometric effects and inductive drive provide < 0.1 V throughout much of the discharge. In contrast to previous analysis of low-field-side (LFS) LHI discharges, which were driven by Veff = 0.3 V and 2.0 V from geometric effects and inductive drive. A significant remaining uncertainty in the model is the resistive dissipation of LHI discharges. This requires greater understanding of LHI confinement scaling and impurity content, which are currently under investigation. However, the model and experimental Ip(t) exhibit good agreement for parameters consistent with previous experimental findings. Extrapolation of plasma parameters and shaping from recent experiments allow for the model to project the performance of LHI systems. These projections indicate Ip 0.3 MA can be accessed on Pegasus via HFS LHI through changes to injector geometry to provide more Veff. This regime can be accessed via a LFS system by increasing the Taylor relaxation current limit early in the discharge. Work supported by US DOE Grants DE-FG02-96ER54375 and DE-SC0006928.

The effect of esophagogastroduodenoscopy probe insertion on the intracuff pressure of airway devices in children during general anesthesia.

PubMed

Balaban, Onur; Kamata, Mineto; Hakim, Mumin; Tumin, Dmitry; Tobias, Joseph D

2017-04-01

Given the size of the esophagogastroduodenoscopy (EGD) probe and the compressibility of the pediatric airway, the EGD probe may increase the intracuff pressure (IP) of an airway device. The current study evaluated IP changes during EGD examination under general anesthesia in pediatric patients. Following the induction of anesthesia, a laryngeal mask airway (LMA) or endotracheal tube (ETT) was placed without neuromuscular blockade. The IP was measured at baseline, during EGD probe insertion, while the EGD probe was in place, and after probe removal. The study cohort included 101 patients (mean age 11.3 years). The airway was secured with an LMA and an ETT in 88 and 13 patients, respectively. The IP increased from 27 ± 15 cmH 2 O at baseline to 34 ± 17 cmH 2 O during probe insertion (p < 0.001), remained at 33 ± 16 cmH 2 O while the probe was in place, and decreased to 26 ± 14 cmH 2 O after probe removal. The IP of the LMA or ETT increased during EGD probe insertion and remained elevated while the probe was in place. High IP may compromise mucosal perfusion resulting in a sore throat when using an LMA or the potential for airway damage if an ETT is used. Removal of air from the cuff and titration of the IP should be considered after EGD insertion.

Voice over Internet protocol for the orthodontic practice: a sensible switch from plain old telephone service.

PubMed

Mupparapu, Muralidhar

2008-03-01

Voice over Internet protocol (VoIP) is a revolutionary new technology that is causing a stir in the telecommunications industry and threatening the existence of traditional telephone service providers. Based on a simple method of converting analog audio signals into digital data before being transmitted over the Internet, VoIP has gained immense popularity among consumers. The technology is now regarded as an alternative to traditional telephone service for the orthodontic office. When the economics are considered, it is cost-effective, especially for a busy orthodontic practice where the call volumes both in and out are always high. VoIP has the potential to reduce costs, break the barriers between local vs long-distance calling, and make life easier for the office staff. However, deploying VoIP requires a cautious and thought-out process. Users should fully understand the risks and benefits before switching from the public switched telephone network. VoIP customers and service providers are vulnerable to many of the same impersonation-based attacks by those who attempt toll fraud, and identity and information theft. In this article, VoIP is introduced to orthodontic practitioners, who might be unfamiliar with this technology. Internet protocol based private branch exchange systems that are currently marketed as open-source technologies are also reviewed. Additionally, VoIP is compared with the traditional public switched telephone network technology and evaluated for its potential applications in an orthodontic office for both increased efficiency and cost savings.

Histone Code Modulation by Oncogenic PWWP-domain Protein in Breast Cancers

DTIC Science & Technology

2012-06-01

imaginal discs, the Drosophila melanogaster homologue of human retinoblastoma binding protein 2. Genetics 2000; 156: 645-663. [10] Zeng J, Ge Z, Wang...in breast cancer patients. Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12...1 Figure 1. Representative view of ChIP-seq peak of a histone modifying factor at the UBR2V2 genomic locus in the

Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1

PubMed Central

Feld, Christine; Sahu, Peeyush; Frech, Miriam; Finkernagel, Florian; Nist, Andrea; Stiewe, Thorsten; Bauer, Uta-Maria; Neubauer, Andreas

2018-01-01

Abstract SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which >40% harbor SKI binding sites in their proximity, primarily in enhancer regions. Gene ontology analysis reveals that many of the differentially expressed genes are annotated to hematopoietic cell differentiation and inflammatory response, corroborating our finding that SKI contributes to a myeloid differentiation block in HL60 cells. We find that SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated SKI targets upon SKI deletion. RUNX1 ChIP-seq displays that nearly 70% of RUNX1 binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1 occupy the same genomic sites and cooperate in gene silencing. Our work demonstrates for the first time the predominant co-repressive function of SKI in AML cells on a genome-wide scale and uncovers the transcription factor RUNX1 as an important mediator of SKI-dependent transcriptional repression. PMID:29471413

Control of IP3-mediated Ca2+ puffs in Xenopus laevis oocytes by the Ca2+-binding protein parvalbumin

PubMed Central

John, Linu M; Mosquera-Caro, Monica; Camacho, Patricia; Lechleiter, James D

2001-01-01

Elementary events of Ca2+ release (Ca2+ puffs) can be elicited from discrete clusters of inositol 1,4,5 trisphosphate receptors (IP3Rs) at low concentrations of IP3. Ca2+ puffs have rarely been observed unless elicited by either hormone treatment or introduction of IP3 into the cell. However, cells appear to have sufficient concentrations of IP3 (0.1-3.0 μM) to induce Ca2+ release under resting conditions. Here, we investigated Ca2+ puff activity in non-stimulated Xenopus oocytes using confocal microscopy. The fluorescent Ca2+ dye indicators Calcium Green 1 and Oregon Green 488 BAPTA-2 were injected into oocytes to monitor basal Ca2+ activity. In this preparation, injection or overexpression of parvalbumin, an EF-hand Ca2+-binding protein (CaBP), induced Ca2+ puffs in resting Xenopus oocytes. This activity was inhibited by heparin, an IP3R channel blocker, and by mutation of the Ca2+-binding sites in parvalbumin. Ca2+ puff activity was also evoked by injection of low concentrations of the Ca2+ chelator EGTA, but not by calbindin D28k, another member of the EF-hand CaBP superfamily. BAPTA and the Ca2+ indicator dye Oregon Green 488 BAPTA-1 evoked Ca2+ puff activity, while the dextran conjugate of Oregon Green 488 BAPTA-1 did not. These data indicate that a Ca2+ buffer must be mobile in order to increase Ca2+ puff activity. Together, the data indicate that some IP3Rs spontaneously release Ca2+ under resting concentrations of IP3. These elementary Ca2+ events appear to be below the level of detection of current imaging techniques. We suggest that parvalbumin evokes Ca2+ puffs by coordinating the activity of elementary IP3R channel openings. We conclude that Ca2+ release can be evoked not only by hormone-induced increases in IP3, but also by expression of mobile cytosolic CaBPs under resting concentrations of IP3. PMID:11507154

Characterization of Ocular Iontophoretic Drug Transport of Ionic and Non-ionic Compounds in Isolated Rabbit Cornea and Conjunctiva.

PubMed

Sekijima, Hidehisa; Ehara, Junya; Hanabata, Yusuke; Suzuki, Takumi; Kimura, Soichiro; Lee, Vincent H L; Morimoto, Yasunori; Ueda, Hideo

2016-06-01

Ocular iontophoresis (IP) in isolated rabbit cornea and conjunctiva was examined in terms of transport enhancement, tissue viability and integrity using electrophysiological parameters by the Ussing-type chamber technique. Lidocaine hydrochloride (LC, a cationic compound), sodium benzoate (BA, anionic compound), and fluorescein isothiocyanate labeled dextran (molecular weight 4400 Da, FD-4, hydrophilic large compound) were used as model permeants. Direct electric current was applied at 0.5-5.0 mA/cm(2) for the cornea and 0.5-20 mA/cm(2) for the conjunctiva for 30 min. LC and BA fluxes across the cornea and conjunctiva were significantly increased by the application of electric current up to 2.3- and 2.5-fold and 4.0- and 3.4-fold, respectively, and returned to their baseline level on stopping the current. Furthermore, a much higher increase by IP application was obtained for the FD-4 transport. The increased FD-4 flux in the conjunctiva returned to baseline on stopping the current, whereas the flux in the cornea was sustained at a higher level after stopping the current. The transepithelial electric resistance of the cornea and conjunctiva was lowered by electric current application but fully recovered after stopping the current up to 2.0 mA/cm(2) for the cornea and 10 mA/cm(2) for the conjunctiva, suggesting that the corneal and conjunctival viability and integrity are maintained even after application of these current densities. These results indicate that ocular IP may be a useful non-invasive technique to achieve drug delivery of hydrophilic large molecules into the eyes.

Role of Peptide YY3-36 and Glucose-Dependent Insulinotropic Polypeptide in Anorexia Induction by Trichothecences T-2 Toxin, HT-2 Toxin, Diacetoxyscirpenol, and Neosolaniol.

PubMed

Zhang, Jie; Jia, Hui; Wang, Qingqing; Zhang, Yajie; Wu, Wenda; Zhang, Haibin

2017-09-01

Trichothecences, secondary metabolites produced by Fusarium, are serious health risks to humans and animals worldwide. Although type A trichothecence-induced food refusal has been observed, the mechanism underlying the anorexia caused by these compounds is not fully understood. In this study, we hypothesized that anorexia induced by type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO), in mice corresponds to the changes in the gut satiety hormones peptide YY3-36 (PYY3-36) and glucose-dependent insulinotropic polypeptide (GIP) in plasma. A well-characterized mouse food refusal model was used in this assay. Oral exposure to or intraperitoneal (ip) injection of 1 mg/kg bw T-2, HT-2, DAS, or NEO resulted in dramatically decreased food intake, and PYY3-36 and GIP concentrations were elevated accordingly. Specifically, the PYY3-36 and GIP concentrations peaked at 2 h following oral exposure to these 4 toxins individually, although the durations were not identical. After ip administration of T-2 or HT-2, PYY3-36 significantly increased within 6 h. However, no significant difference was found in the DAS and NEO groups. The GIP levels peaked within 2, 2, 0.5, and 0.5 h, respectively, and remained increased up to 6, 6, 2, and 6 h, respectively, following T-2, HT-2, DAS, or NEO ip exposure. The increase in GIP was greater than that of PYY3-36 after exposure to the 4 toxins using 2 administration routes. Together, these findings suggest that PYY3-36 and GIP play a role in T-2-, HT-2-, DAS-, and NEO-induced anorexia. © 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.

Cross State-dependent Learning Interaction Between Scopolamine and Morphine in Mice: The Role of Dorsal Hippocampus

PubMed Central

Maleki, Morteza; Hassanpour-Ezatti, Majid; Navaeian, Majid

2017-01-01

Introduction: The current study aimed at investigating the existence of the cross state-dependent learning between morphine and scopolamine (SCO) in mice by passive avoidance method, pointing to the role of CA1 area. Methods: The effects of pre-training SCO (0.75, 1.5, and 3 μg, Intra-CA1), or morphine (1, 3, and 6 mg/kg, intraperitoneal (i.p.) was evaluated on the retrieval of passive avoidance learning using step-down task in mice (n=10). Then, the effect of pretest administration of morphine (1.5, 3, and 6 mg/kg, i.p.) was examined on passive avoidance retrieval impairment induced by pre-training SCO (3 μg/mice, Intra-CA1). Next, the effect of pretest Intra-CA1 injection of scopolamine (0.75, 1.5, and 3 μg/mice) was evaluated on morphine (6 mg/kg, i.p.) pre-training deficits in this task in mice. Results: The pre-training Intra-CA1 injection of scopolamine (1.5 and 3 μg/mouse), or morphine (3 and 6 mg/kg, i.p.) impaired the avoidance memory retrieval when it was tested 24 hours later. Pretest injection of both drugs improved its pre-training impairing effects on mice memory. Moreover, the amnesia induced by the pre-training injections of scopolamine (3 μg/mice) was restored significantly (P<0.01) by pretest injections of morphine (3 and 6 mg/kg, i.p.). Similarly, pretest injection of scopolamine (3 μg/mice) restored amnesia induced by the pre-training injections of morphine (6 mg/kg, i.p.), significantly (P<0.01). Conclusion: The current study findings indicated a cross state-dependent learning between SCO and morphine at CA1 level. Therefore, it seems that muscarinic and opioid receptors may act reciprocally on modulation of passive avoidance memory retrieval, at the level of dorsal hippocampus, in mice. PMID:28781727

HIGH-TIME-RESOLUTION MEASUREMENTS OF THE POLARIZATION OF THE CRAB PULSAR AT 1.38 GHz

DOE Office of Scientific and Technical Information (OSTI.GOV)

Słowikowska, Agnieszka; Stappers, Benjamin W.; Harding, Alice K.

2015-01-20

Using the Westerbork Synthesis Radio Telescope, we obtained high-time-resolution measurements of the full polarization of the Crab pulsar. At a resolution of 1/8192 of the 34 ms pulse period (i.e., 4.1 μs), the 1.38 GHz linear-polarization measurements are in general agreement with previous lower-time-resolution 1.4 GHz measurements of linear polarization in the main pulse (MP), in the interpulse (IP), and in the low-frequency component (LFC). We find the MP and IP to be linearly polarized at about 24% and 21% with no discernible difference in polarization position angle. However, contrary to theoretical expectations and measurements in the visible, we find nomore » evidence for significant variation (sweep) in the polarization position angle over the MP, the IP, or the LFC. We discuss the implications, which appear to be in contradiction to theoretical expectations. We also detect weak circular polarization in the MP and IP, and strong (≈20%) circular polarization in the LFC, which also exhibits very strong (≈98%) linear polarization at a position angle of 40° from that of the MP or IP. The properties are consistent with the LFC, which is a low-altitude component, and the MP and IP, which are high-altitude caustic components. Current models for the MP and IP emission do not readily account for the absence of pronounced polarization changes across the pulse. We measure IP and LFC pulse phases relative to the MP consistent with recent measurements, which have shown that the phases of these pulse components are evolving with time.« less

The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test.

PubMed

Khan, Muhammad Imran; Ostadhadi, Sattar; Zolfaghari, Samira; Ejtemaei Mehr, Shahram; Hassanzadeh, Gholamreza; Dehpour, Ahmad-Reza

2016-01-26

In the current study, the involvement of N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in the antidepressant-like effects of baclofen was evaluated by using animal model in forced swimming test. Followed by an open field test for the evaluation of locomotor activity, the immobility time for mice in force swimming test was recorded. Only the last four min was analyzed. Administration of Baclofen (0.5 and 1mg/kg, i.p.) reduced the immobility interval in the FST. Prior administration of l-arginine (750mg/kg, i.p.,) a nitric oxide synthase substrate or sildenafil (5mg/kg, i.p.) a phosphodiesterase 5 into mice suppressed the antidepressant-like activity of baclofen (1mg/kg, i.p.).Co-treatment of 7-nitroindazole (50mg/kg, i.p.,) an inhibitor of neuronal nitric oxide synthase, L-NAME (10mg/kg, i.p.,) a non-specific inhibitor of nitric oxide synthase or MK-801 (0.05mg/kg, i.p.) an NMDA receptor antagonist with subeffective dose of baclofen (0.1mg/kg, i.p.), reduced the immobility time in the FST as compared to the drugs when used alone. Co-administrated of lower doses of MK-801 (0.01mg/kg) or l-NAME (1mg/kg) failed to effect immobility time however, simultaneous administration of these two agents in same dose with subeffective dose of baclofen (0.1mg/kg, i.p.), minimized the immobility time in the FST. Thus, our results support the role of NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant-like action of baclofen. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Coherent Coupled Qubits for Quantum Annealing

NASA Astrophysics Data System (ADS)

Weber, Steven J.; Samach, Gabriel O.; Hover, David; Gustavsson, Simon; Kim, David K.; Melville, Alexander; Rosenberg, Danna; Sears, Adam P.; Yan, Fei; Yoder, Jonilyn L.; Oliver, William D.; Kerman, Andrew J.

2017-07-01

Quantum annealing is an optimization technique which potentially leverages quantum tunneling to enhance computational performance. Existing quantum annealers use superconducting flux qubits with short coherence times limited primarily by the use of large persistent currents Ip. Here, we examine an alternative approach using qubits with smaller Ip and longer coherence times. We demonstrate tunable coupling, a basic building block for quantum annealing, between two flux qubits with small (approximately 50-nA) persistent currents. Furthermore, we characterize qubit coherence as a function of coupler setting and investigate the effect of flux noise in the coupler loop on qubit coherence. Our results provide insight into the available design space for next-generation quantum annealers with improved coherence.

Stability analysis of the high poloidal bet scenario on DIII-Dtowards operation athigher plasma current

NASA Astrophysics Data System (ADS)

Guo, W. F.; Gong, X. Z.; Huang, J.; Ren, Q. L.; Qian, J. P.; Ding, S. Y.; Pan, C. K.; Li, G. Q.; Xia, T. Y.; Garofalo, A. M.; Lao, L.; Hyatt, A.; Ferron, J.; Meneghini, O.; Liu, Y. Q.; McClenaghan, J.; Holcomb, C. T.

2017-10-01

The high poloidal beta scenario with plasma current IP 600 kA and large-radius internal transport barrier (ITB) on DIII-D is subject to n =1 MHD kink modes when the current profile becomes very broad at internal inductance values li 0.5-0.6. It is desirable to extend this scenario to higer plasma current ( 1 MA) for highernormalized fusionperformance. However, higher current at constant normalized beta, ?N 3, would reducethe poloidal bet, ?P, below the threshold for ITB sustainment, observed at ?P 1.9. Thus, to avoid loss of the IT, ?N?? must be increased together with IP while avoiding the kink instability. MHD analysis is presented that explains possible paths to high ?N stability limit for the kink mode in tis scenario. Work supported by National Magnetic Confinement Fusion Program of Chin under 2015GB110001 and 2015GB102000 - National Natural Science Foundation of China under Grant No. 1147521 and by US DOE under DE-FC02-04ER54698.

An Improved Harmonic Current Detection Method Based on Parallel Active Power Filter

NASA Astrophysics Data System (ADS)

Zeng, Zhiwu; Xie, Yunxiang; Wang, Yingpin; Guan, Yuanpeng; Li, Lanfang; Zhang, Xiaoyu

2017-05-01

Harmonic detection technology plays an important role in the applications of active power filter. The accuracy and real-time performance of harmonic detection are the precondition to ensure the compensation performance of Active Power Filter (APF). This paper proposed an improved instantaneous reactive power harmonic current detection algorithm. The algorithm uses an improved ip -iq algorithm which is combined with the moving average value filter. The proposed ip -iq algorithm can remove the αβ and dq coordinate transformation, decreasing the cost of calculation, simplifying the extraction process of fundamental components of load currents, and improving the detection speed. The traditional low-pass filter is replaced by the moving average filter, detecting the harmonic currents more precisely and quickly. Compared with the traditional algorithm, the THD (Total Harmonic Distortion) of the grid currents is reduced from 4.41% to 3.89% for the simulations and from 8.50% to 4.37% for the experiments after the improvement. The results show the proposed algorithm is more accurate and efficient.

Speech transport for packet telephony and voice over IP

NASA Astrophysics Data System (ADS)

Baker, Maurice R.

1999-11-01

Recent advances in packet switching, internetworking, and digital signal processing technologies have converged to allow realizable practical implementations of packet telephony systems. This paper provides a tutorial on transmission engineering for packet telephony covering the topics of speech coding/decoding, speech packetization, packet data network transport, and impairments which may negatively impact end-to-end system quality. Particular emphasis is placed upon Voice over Internet Protocol given the current popularity and ubiquity of IP transport.

ASN reputation system model

NASA Astrophysics Data System (ADS)

Hutchinson, Steve; Erbacher, Robert F.

2015-05-01

Network security monitoring is currently challenged by its reliance on human analysts and the inability for tools to generate indications and warnings for previously unknown attacks. We propose a reputation system based on IP address set membership within the Autonomous System Number (ASN) system. Essentially, a metric generated based on the historic behavior, or misbehavior, of nodes within a given ASN can be used to predict future behavior and provide a mechanism to locate network activity requiring inspection. This will provide reinforcement of notifications and warnings and lead to inspection for ASNs known to be problematic even if initial inspection leads to interpretation of the event as innocuous. We developed proof of concept capabilities to generate the IP address to ASN set membership and analyze the impact of the results. These results clearly show that while some ASNs are one-offs with individual or small numbers of misbehaving IP addresses, there are definitive ASNs with a history of long term and wide spread misbehaving IP addresses. These ASNs with long histories are what we are especially interested in and will provide an additional correlation metric for the human analyst and lead to new tools to aid remediation of these IP address blocks.

Point-source helicity injection for ST plasma startup in Pegasus

NASA Astrophysics Data System (ADS)

Redd, A. J.; Battaglia, D. J.; Bongard, M. W.; Fonck, R. J.; Schlossberg, D. J.

2009-11-01

Plasma current guns are used as point-source DC helicity injectors for forming non-solenoidal tokamak plasmas in the Pegasus Toroidal Experiment. Discharges driven by this injection scheme have achieved Ip>= 100 kA using Iinj<= 4 kA. They form at the outboard midplane, transition to a tokamak-like equilibrium, and continue to grow inward as Ip increases due to helicity injection and outer- PF induction. The maximum Ip is determined by helicity balance (injection rate vs resistive dissipation) and a Taylor relaxation limit, in which Ip√ITF Iinj/w, where w is the radial thickness of the gun-driven edge. Preliminary experiments tentatively confirm these scalings with ITF, Iinj, and w, increasing confidence in this simple relaxation model. Adding solenoidal inductive drive during helicity injection can push Ip up to, but not beyond, the predicted relaxation limit, demonstrating that this is a hard performance limit. Present experiments are focused on increasing the injection voltage (i.e., helicity injection rate) and reducing w. Near-term goals are to further test scalings predicted by the simple relaxation model and to study in detail the observed bursty n=1 activity correlated with rapid increases in Ip.

A mathematical model for maximizing the value of phase 3 drug development portfolios incorporating budget constraints and risk.

PubMed

Patel, Nitin R; Ankolekar, Suresh; Antonijevic, Zoran; Rajicic, Natasa

2013-05-10

We describe a value-driven approach to optimizing pharmaceutical portfolios. Our approach incorporates inputs from research and development and commercial functions by simultaneously addressing internal and external factors. This approach differentiates itself from current practices in that it recognizes the impact of study design parameters, sample size in particular, on the portfolio value. We develop an integer programming (IP) model as the basis for Bayesian decision analysis to optimize phase 3 development portfolios using expected net present value as the criterion. We show how this framework can be used to determine optimal sample sizes and trial schedules to maximize the value of a portfolio under budget constraints. We then illustrate the remarkable flexibility of the IP model to answer a variety of 'what-if' questions that reflect situations that arise in practice. We extend the IP model to a stochastic IP model to incorporate uncertainty in the availability of drugs from earlier development phases for phase 3 development in the future. We show how to use stochastic IP to re-optimize the portfolio development strategy over time as new information accumulates and budget changes occur. Copyright © 2013 John Wiley & Sons, Ltd.

Lightweight SIP/SDP compression scheme (LSSCS)

NASA Astrophysics Data System (ADS)

Wu, Jian J.; Demetrescu, Cristian

2001-10-01

In UMTS new IP based services with tight delay constraints will be deployed over the W-CDMA air interface such as IP multimedia and interactive services. To integrate the wireline and wireless IP services, 3GPP standard forum adopted the Session Initiation Protocol (SIP) as the call control protocol for the UMTS Release 5, which will implement next generation, all IP networks for real-time QoS services. In the current form the SIP protocol is not suitable for wireless transmission due to its large message size which will need either a big radio pipe for transmission or it will take far much longer to transmit than the current GSM Call Control (CC) message sequence. In this paper we present a novel compression algorithm called Lightweight SIP/SDP Compression Scheme (LSSCS), which acts at the SIP application layer and therefore removes the information redundancy before it is sent to the network and transport layer. A binary octet-aligned header is added to the compressed SIP/SDP message before sending it to the network layer. The receiver uses this binary header as well as the pre-cached information to regenerate the original SIP/SDP message. The key features of the LSSCS compression scheme are presented in this paper along with implementation examples. It is shown that this compression algorithm makes SIP transmission efficient over the radio interface without losing the SIP generality and flexibility.

ChiLin: a comprehensive ChIP-seq and DNase-seq quality control and analysis pipeline.

PubMed

Qin, Qian; Mei, Shenglin; Wu, Qiu; Sun, Hanfei; Li, Lewyn; Taing, Len; Chen, Sujun; Li, Fugen; Liu, Tao; Zang, Chongzhi; Xu, Han; Chen, Yiwen; Meyer, Clifford A; Zhang, Yong; Brown, Myles; Long, Henry W; Liu, X Shirley

2016-10-03

Transcription factor binding, histone modification, and chromatin accessibility studies are important approaches to understanding the biology of gene regulation. ChIP-seq and DNase-seq have become the standard techniques for studying protein-DNA interactions and chromatin accessibility respectively, and comprehensive quality control (QC) and analysis tools are critical to extracting the most value from these assay types. Although many analysis and QC tools have been reported, few combine ChIP-seq and DNase-seq data analysis and quality control in a unified framework with a comprehensive and unbiased reference of data quality metrics. ChiLin is a computational pipeline that automates the quality control and data analyses of ChIP-seq and DNase-seq data. It is developed using a flexible and modular software framework that can be easily extended and modified. ChiLin is ideal for batch processing of many datasets and is well suited for large collaborative projects involving ChIP-seq and DNase-seq from different designs. ChiLin generates comprehensive quality control reports that include comparisons with historical data derived from over 23,677 public ChIP-seq and DNase-seq samples (11,265 datasets) from eight literature-based classified categories. To the best of our knowledge, this atlas represents the most comprehensive ChIP-seq and DNase-seq related quality metric resource currently available. These historical metrics provide useful heuristic quality references for experiment across all commonly used assay types. Using representative datasets, we demonstrate the versatility of the pipeline by applying it to different assay types of ChIP-seq data. The pipeline software is available open source at https://github.com/cfce/chilin . ChiLin is a scalable and powerful tool to process large batches of ChIP-seq and DNase-seq datasets. The analysis output and quality metrics have been structured into user-friendly directories and reports. We have successfully compiled 23,677 profiles into a comprehensive quality atlas with fine classification for users.

Host responses to interspecific brood parasitism: a by-product of adaptations to conspecific parasitism?

PubMed Central

2014-01-01

Background Why have birds evolved the ability to reject eggs? Typically, foreign egg discrimination is interpreted as evidence that interspecific brood parasitism (IP) has selected for the host’s ability to recognize and eliminate foreign eggs. Fewer studies explore the alternative hypothesis that rejection of interspecific eggs is a by-product of host defenses, evolved against conspecific parasitism (CP). We performed a large scale study with replication across taxa (two congeneric Turdus thrushes), space (populations), time (breeding seasons), and treatments (three types of experimental eggs), using a consistent design of egg rejection experiments (n = 1057 nests; including controls), in areas with potential IP either present (Europe; native populations) or absent (New Zealand; introduced populations). These comparisons benefited from the known length of allopatry (one and a half centuries), with no gene flow between native and introduced populations, which is rarely available in host-parasite systems. Results Hosts rejected CP at unusually high rates for passerines (up to 60%). CP rejection rates were higher in populations with higher conspecific breeding densities and no risks of IP, supporting the CP hypothesis. IP rejection rates did not covary geographically with IP risk, contradicting the IP hypothesis. High egg rejection rates were maintained in the relatively long-term isolation from IP despite non-trivial rejection costs and errors. Conclusions These egg rejection patterns, combined with recent findings that these thrushes are currently unsuitable hosts of the obligate parasitic common cuckoo (Cuculus canorus), are in agreement with the hypothesis that the rejection of IP is a by-product of fine-tuned egg discrimination evolved due to CP. Our study highlights the importance of considering both IP and CP simultaneously as potential drivers in the evolution of egg discrimination, and illustrates how populations introduced to novel ecological contexts can provide critical insights into brood parasite-host coevolution. PMID:24834103

Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach

PubMed Central

Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

2015-01-01

Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in preclinical settings. PMID:25785453

Non-viral generation of marmoset monkey iPS cells by a six-factor-in-one-vector approach.

PubMed

Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

2015-01-01

Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in preclinical settings.

Host responses to interspecific brood parasitism: a by-product of adaptations to conspecific parasitism?

PubMed

Samas, Peter; Hauber, Mark E; Cassey, Phillip; Grim, Tomas

2014-01-01

Why have birds evolved the ability to reject eggs? Typically, foreign egg discrimination is interpreted as evidence that interspecific brood parasitism (IP) has selected for the host's ability to recognize and eliminate foreign eggs. Fewer studies explore the alternative hypothesis that rejection of interspecific eggs is a by-product of host defenses, evolved against conspecific parasitism (CP). We performed a large scale study with replication across taxa (two congeneric Turdus thrushes), space (populations), time (breeding seasons), and treatments (three types of experimental eggs), using a consistent design of egg rejection experiments (n = 1057 nests; including controls), in areas with potential IP either present (Europe; native populations) or absent (New Zealand; introduced populations). These comparisons benefited from the known length of allopatry (one and a half centuries), with no gene flow between native and introduced populations, which is rarely available in host-parasite systems. Hosts rejected CP at unusually high rates for passerines (up to 60%). CP rejection rates were higher in populations with higher conspecific breeding densities and no risks of IP, supporting the CP hypothesis. IP rejection rates did not covary geographically with IP risk, contradicting the IP hypothesis. High egg rejection rates were maintained in the relatively long-term isolation from IP despite non-trivial rejection costs and errors. These egg rejection patterns, combined with recent findings that these thrushes are currently unsuitable hosts of the obligate parasitic common cuckoo (Cuculus canorus), are in agreement with the hypothesis that the rejection of IP is a by-product of fine-tuned egg discrimination evolved due to CP. Our study highlights the importance of considering both IP and CP simultaneously as potential drivers in the evolution of egg discrimination, and illustrates how populations introduced to novel ecological contexts can provide critical insights into brood parasite-host coevolution.

Integrated modeling of plasma ramp-up in DIII-D ITER-like and high bootstrap current scenario discharges

NASA Astrophysics Data System (ADS)

Wu, M. Q.; Pan, C. K.; Chan, V. S.; Li, G. Q.; Garofalo, A. M.; Jian, X.; Liu, L.; Ren, Q. L.; Chen, J. L.; Gao, X.; Gong, X. Z.; Ding, S. Y.; Qian, J. P.; Cfetr Physics Team

2018-04-01

Time-dependent integrated modeling of DIII-D ITER-like and high bootstrap current plasma ramp-up discharges has been performed with the equilibrium code EFIT, and the transport codes TGYRO and ONETWO. Electron and ion temperature profiles are simulated by TGYRO with the TGLF (SAT0 or VX model) turbulent and NEO neoclassical transport models. The VX model is a new empirical extension of the TGLF turbulent model [Jian et al., Nucl. Fusion 58, 016011 (2018)], which captures the physics of multi-scale interaction between low-k and high-k turbulence from nonlinear gyro-kinetic simulation. This model is demonstrated to accurately model low Ip discharges from the EAST tokamak. Time evolution of the plasma current density profile is simulated by ONETWO with the experimental current ramp-up rate. The general trend of the predicted evolution of the current density profile is consistent with that obtained from the equilibrium reconstruction with Motional Stark effect constraints. The predicted evolution of βN , li , and βP also agrees well with the experiments. For the ITER-like cases, the predicted electron and ion temperature profiles using TGLF_Sat0 agree closely with the experimental measured profiles, and are demonstrably better than other proposed transport models. For the high bootstrap current case, the predicted electron and ion temperature profiles perform better in the VX model. It is found that the SAT0 model works well at high IP (>0.76 MA) while the VX model covers a wider range of plasma current ( IP > 0.6 MA). The results reported in this paper suggest that the developed integrated modeling could be a candidate for ITER and CFETR ramp-up engineering design modeling.

Chloride secretagogues stimulate inositol phosphate formation in shark rectal gland tubules cultured in suspension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ecay, T.W.; Valentich, J.D.

1991-03-01

Neuroendocrine activation of transepithelial chloride secretion by shark rectal gland cells is associated with increases in cellular cAMP, cGMP, and free calcium concentrations. We report here on the effects of several chloride secretagogues on inositol phosphate formation in cultured rectal gland tubules. Vasoactive intestinal peptide (VIP), atriopeptin (AP), and ionomycin increase the total inositol phosphate levels of cultured tubules, as measured by ion exchange chromatography. Forskolin, a potent chloride secretagogue, has no effect on inositol phosphate formation. The uptake of {sup 3}H-myo-inositol into phospholipids is very slow, preventing the detection of increased levels of inositol trisphosphate. However, significant increases inmore » inositol monophosphate (IP1) and inositol biphosphate (IP2) were measured. The time course of VIP- and AP-stimulated IP1 and IP2 formation is similar to the effects of these agents on the short-circuit current responses of rectal gland monolayer cultures. In addition, aluminum fluoride, an artificial activator of guanine nucleotide-binding proteins, stimulates IP1 and IP2 formation. We conclude that rectal gland cells contain VIP and AP receptors coupled to the activation of phospholipase C. Coupling may be mediated by G-proteins. Receptor-stimulated increases in inositol phospholipid metabolism is one mechanism leading to increased intracellular free calcium concentrations, an important regulatory event in the activation of transepithelial chloride secretion by shark rectal gland epithelial cells.« less

Are Current Insulin Pumps Accessible to Blind and Visually Impaired People?

PubMed Central

Burton, Darren M.; Uslan, Mark M.; Blubaugh, Morgan V.; Clements, Charles W.

2009-01-01

Background In 2004, Uslan and colleagues determined that insulin pumps (IPs) on the market were largely inaccessible to blind and visually impaired persons. The objective of this study is to determine if accessibility status changed in the ensuing 4 years. Methods Five IPs on the market in 2008 were acquired and analyzed for key accessibility traits such as speech and other audio output, tactual nature of control buttons, and the quality of visual displays. It was also determined whether or not a blind or visually impaired person could independently complete tasks such as programming the IP for insulin delivery, replacing batteries, and reading manuals and other documentation. Results It was found that IPs have not improved in accessibility since 2004. None have speech output, and with the exception of the Animas IR 2020, no significantly improved visual display characteristics were found. Documentation is still not completely accessible. Conclusion Insulin pumps are relatively complex devices, with serious health consequences resulting from improper use. For IPs to be used safely and independently by blind and visually impaired patients, they must include voice output to communicate all the information presented on their display screens. Enhancing display contrast and the size of the displayed information would also improve accessibility for visually impaired users. The IPs must also come with accessible user documentation in alternate formats. PMID:20144301

Are current insulin pumps accessible to blind and visually impaired people?

PubMed

Burton, Darren M; Uslan, Mark M; Blubaugh, Morgan V; Clements, Charles W

2009-05-01

In 2004, Uslan and colleagues determined that insulin pumps (IPs) on the market were largely inaccessible to blind and visually impaired persons. The objective of this study is to determine if accessibility status changed in the ensuing 4 years. Five IPs on the market in 2008 were acquired and analyzed for key accessibility traits such as speech and other audio output, tactual nature of control buttons, and the quality of visual displays. It was also determined whether or not a blind or visually impaired person could independently complete tasks such as programming the IP for insulin delivery, replacing batteries, and reading manuals and other documentation. It was found that IPs have not improved in accessibility since 2004. None have speech output, and with the exception of the Animas IR 2020, no significantly improved visual display characteristics were found. Documentation is still not completely accessible. Insulin pumps are relatively complex devices, with serious health consequences resulting from improper use. For IPs to be used safely and independently by blind and visually impaired patients, they must include voice output to communicate all the information presented on their display screens. Enhancing display contrast and the size of the displayed information would also improve accessibility for visually impaired users. The IPs must also come with accessible user documentation in alternate formats. 2009 Diabetes Technology Society.

Infection prevention workforce: Potential benefits to educational diversity.

PubMed

Reese, Sara M; Gilmartin, Heather M

2017-06-01

Nurses have historically occupied the infection preventionist (IP) role. As the knowledge and skills needed to advance the field expand, professionals from public health and the laboratory sciences have become IPs. Our study describes the characteristics of current IPs and assesses for relationships between background, certification, experience, and type of work performed. The data were drawn from an existing dataset collected in the conduct of the Association for Professionals in Infection Control and Epidemiology (APIC) MegaSurvey. Descriptive statistics were computed. Associations were calculated using χ 2 or Cochran-Mantel-Haenszel tests. Characteristics of IPs were stratified by work-related activities to allow for comparisons between groups. Of the 13,050 active APIC members, 4,079 participated in the survey (31% response rate). The primary job activity for nurses (97.9%; n = 2,434) was preventing and controlling the transmission of infectious agents or health care-associated infections, for laboratory scientists (97.5%; n = 307) it was the interpretation of surveillance data, and for public health professionals (96.1%; n = 136) it was management and communication: feedback. Infection control departments would benefit from hiring IPs with diverse education and training to address the expanding roles and responsibilities of IPs. This may facilitate the implementation of novel and innovative processes that will impact patient care. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

SN 2015bh: an LBV becomes NGC 2770s fourth SN. . . or not?

NASA Astrophysics Data System (ADS)

Thöne, Christina C.; de Ugarte Postigo, Antonio; Leloudas, Giorgos

2017-11-01

Massive stars in the final phases of their lives frequently expel large amounts of material. An interesting example is SN 2009ip that varied in brightness years before its possible core-collapse. Here we present SN 2015bh in NGC 2770 that shows striking similarities to SN 2009ip. It experienced frequent variabilities for 21 years before a smaller precursor and the ``main event'' in May 2015. Its spectra are consistent with an LBV during the outburst phase and show a complex P-Cygni profile during the main event. Both SN 2009ip and 2015bh were always situated red-wards of LBVs in outburst in the HR diagram. Their final fate is currently still uncertain, SN 2009ip, however, is now fainter than in pre-explosion observations. If the star survives this event it is undoubtedly altered, and we suggest that these ``zombie stars'' could be LBVs evolving into a Wolf-Rayet (WR) star over a very short timescale.

Induced pluripotent stem (iPS) cells: a new source for cell-based therapeutics?

PubMed

de Lázaro, Irene; Yilmazer, Açelya; Kostarelos, Kostas

2014-07-10

The generation of induced pluripotent stem (iPS) cells from somatic cells by the ectopic expression of defined transcription factors has provided the regenerative medicine field with a new tool for cell replacement strategies. The advantages that these pluripotent cells can offer in comparison to other sources of stem cells include the generation of patient-derived cells and the lack of embryonic tissue while maintaining a versatile differentiation potential. The promise of iPS cell derivatives for therapeutic applications is encouraging albeit very early in development, with the first clinical study currently ongoing in Japan. Many challenges are yet to be circumvented before this technology can be clinically translated widely though. The delivery and expression of the reprogramming factors, the genomic instability, epigenetic memory and impact of cell propagation in culture are only some of the concerns. This article aims to critically discuss the potential of iPS cells as a new source of cell therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

Induced Pluripotent Stem Cell-Derived Red Blood Cells and Platelet Concentrates: From Bench to Bedside.

PubMed

Focosi, Daniele; Amabile, Giovanni

2017-12-27

Red blood cells and platelets are anucleate blood components indispensable for oxygen delivery and hemostasis, respectively. Derivation of these blood elements from induced pluripotent stem (iPS) cells has the potential to develop blood donor-independent and genetic manipulation-prone products to complement or replace current transfusion banking, also minimizing the risk of alloimmunization. While the production of erythrocytes from iPS cells has challenges to overcome, such as differentiation into adult-type phenotype that functions properly after transfusion, platelet products are qualitatively and quantitatively approaching a clinically-applicable level owing to advances in expandable megakaryocyte (MK) lines, platelet-producing bioreactors, and novel reagents. Guidelines that assure the quality of iPS cells-derived blood products for clinical application represent a novel challenge for regulatory agencies. Considering the minimal risk of tumorigenicity and the expected significant demand of such products, ex vivo production of iPS-derived blood components can pave the way for iPS translation into the clinic.

Multireference configuration interaction calculations of the first six ionization potentials of the uranium atom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bross, David H.; Parmar, Payal; Peterson, Kirk A.

The first 6 ionization potentials (IPs) of the uranium atom have been calculated using multireference configuration interaction (MRCI+Q) with extrapolations to the complete basis set (CBS) limit using new all-electron correlation consistent basis sets. The latter were carried out with the third-order Douglas-Kroll-Hess Hamiltonian. Correlation down through the 5s5p5d electrons have been taken into account, as well as contributions to the IPs due to the Lamb shift. Spin-orbit coupling contributions calculated at the 4-component Kramers restricted configuration interaction level, as well as the Gaunt term computed at the Dirac-Hartree-Fock level, were added to the best scalar relativistic results. As amore » result, the final ionization potentials are expected to be accurate to at least 5 kcal/mol (0.2 eV), and thus more reliable than the current experimental values of IP 3 through IP 6.« less

Team Faces Tough Odds to Implement New Phone Network | Poster

Cancer.gov

It was a Saturday, in the final stretch of winter in late February, and the temperature peaked to a pleasant 66 degrees. Many people were outside enjoying the spring-like weather; however, the Voice over Internet Protocol (VoIP) Deployment Team was hard at work at Industry Lane. The team of 10 was installing the new voice-only network, including deploying 145 phones, switching and testing the 911 feature, connecting wall mounts, and verifying each phone... Read more

The Science and Ethics of Induced Pluripotency: What Will Become of Embryonic Stem Cells?

PubMed Central

Zacharias, David G.; Nelson, Timothy J.; Mueller, Paul S.; Hook, C. Christopher

2011-01-01

For over a decade, the field of stem cell research has advanced tremendously and gained new attention in light of novel insights and emerging developments for regenerative medicine. Invariably, multiple considerations come into play, and clinicians and researchers must weigh the benefits of certain stem cell platforms against the costs they incur. Notably, human embryonic stem (hES) cell research has been a source of continued debate, leading to differing policies and regulations worldwide. This article briefly reviews current stem cell platforms, looking specifically at the two existing pluripotent lines available for potential therapeutic applications: hES cells and induced pluripotent stem (iPS) cells. We submit iPS technology as a viable and possibly superior alternative for future medical and research endeavors as it obviates many ethical and resource-related concerns posed by hES cells while prospectively matching their potential for scientific use. However, while the clinical realities of iPS cells appear promising, we must recognize the current limitations of this technology, avoid hype, and articulate ethically acceptable medical and scientific goals. PMID:21719620

Method and apparatus for current-output peak detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Geronimo, Gianluigi

2017-01-24

A method and apparatus for a current-output peak detector. A current-output peak detector circuit is disclosed and works in two phases. The peak detector circuit includes switches to switch the peak detector circuit from the first phase to the second phase upon detection of the peak voltage of an input voltage signal. The peak detector generates a current output with a high degree of accuracy in the second phase.

Current responsive devices for synchronous generators

DOEpatents

Karlicek, Robert F.

1983-01-01

A device for detecting current imbalance between phases of a polyphase alternating current generator. A detector responds to the maximum peak current in the generator, and detecting means generates an output for each phase proportional to the peak current of each phase. Comparing means generates an output when the maximum peak current exceeds the phase peak current.

Dual chronoamperometric detection of enzymatic biomarkers using magnetic beads and a low-cost flow cell.

PubMed

Moral-Vico, Javier; Barallat, Jaume; Abad, Llibertat; Olivé-Monllau, Rosa; Muñoz-Pascual, Francesc Xavier; Galán Ortega, Amparo; del Campo, F Javier; Baldrich, Eva

2015-07-15

In this work we report on the production of a low cost microfluidic device for the multiplexed electrochemical detection of magneto bioassays. As a proof of concept, the device has been used to detect myeloperoxidase (MPO), a cardiovascular biomarker. With this purpose, two bioassays have been optimized in parallel onto magnetic beads (MBs) for the simultaneous detection of MPO endogenous peroxidase activity and quantification of total MPO. Since the two bioassays produced signals of different magnitude for each concentration of MPO tested, two detection strategies have been compared, which entailed registering steady state currents (Iss) under substrate flow, and measuring the peak currents (Ip) produced in a stopped flow approach. As it will be shown, appropriate tuning of the detection and flow conditions can provide extremely sensitive detection, but also allow simultaneous detection of assays or parameters that would produce signals of different orders of magnitude when measured by a single detection strategy. In order to demonstrate the feasibility of the detection strategy reported, a dual MPO mass and activity assay has been finally applied to the study of 10 real plasma samples, allowing patient classification according to the risk of suffering a cardiovascular event. Copyright © 2015 Elsevier B.V. All rights reserved.

An assessment of ten ocean reanalyses in the polar regions

NASA Astrophysics Data System (ADS)

Uotila, Petteri

2017-04-01

Ocean reanalysis (ORA) combines observations either statistically or with a hydrodynamical model, to reconstruct historical changes in the ocean. Global and regional ORA products are increasingly used in polar research, but their quality remains to be systematically assessed. To address this, the Polar ORA Intercomparison Project (PORA-IP) has been established following on from the ORA-IP project (Balmaseda et al. 2015, with other papers in a special issue of Climate Dynamics). The PORA-IP is constituted under the COST EOS initiative with plans to review reanalyses products in both the Arctic and Antarctic, and is endorsed by YOPP - the Year of Polar Prediction project. Currently, the PORA-IP team consists of 21 researchers from 15 institutes and universities. The ORA-IP products with polar physics, such as sea ice, have been updated where necessary and collected in a public database. In addition to model output, available observational polar climatologies are collected and used in the assessments. Due to the extensive variety of products, this database should become a valuable resource outside the PORA-IP community. For a comprehensive evaluation of the ten ORA products (CGLORSv5, ECDA3.1, GECCO2, Glorys2v4, GloSea5_GO5, MOVEG2i, ORAP5, SODA3.3.1, TOPAZ4 and UR025.4) in the Arctic and Southern Oceans several specific diagnostics are assessed. The PORA-IP diagnostics target the following topics: hydrography; heat, salinity and freshwater content; ocean transports and surface currents; mixed layer depth; sea-ice concentration and thickness; and snow thickness over sea ice. Based on these diagnostics, ORA product biases against observed data and their mutual spread are quantified, and possible reasons for discrepancies discussed. So far, we have identified product outliers and evaluated the multi-model mean. We have identified the importance of the atmospheric forcing, air-ocean coupling protocol and sea-ice data assimilation for the product performance. Moreover, we are investigating co-variability between the Arctic Ocean heat content and the North Atlantic heat transport, and between the mixed layer depth, oceanic convection, the upper ocean hydrography and sea ice. We will also present other diagnostic results which provide closely related information for those interested in enhancing model predictive skill over a range of time scales, including seasonal to decadal.

Comprehensive hydrophilic interaction and ion-pair reversed-phase liquid chromatography for analysis of di- to deca-oligonucleotides.

PubMed

Li, Qin; Lynen, Frédéric; Wang, Jian; Li, Hanlin; Xu, Guowang; Sandra, Pat

2012-09-14

A comprehensive two-dimensional HPLC approach with a high degree of orthogonality was developed for analysis of di- to deca-oligonucleotides (ONs). Hydrophilic interaction liquid chromatography (HILIC) was used in the first dimension, and ion-pair reversed-phase liquid chromatography (IP-RPLC) was employed in the second dimension. The two dimensions were connected via a ten-port valve interface equipped with octadecyl silica (ODS) traps to immobilize and focus the ONs eluting from the first dimension prior to IP-RPLC separation. An aqueous make-up flow was used for effective trapping. The comprehensive two-dimensional HPLC system was optimized with a mixture consisting of 27 oligonucleotide standards. An overall chromatographic peak capacity of 500 was obtained. The use of the volatile buffer triethylamine acetate in the second dimension allowed straightforward coupling to electrospray ionization mass spectrometry (ESI-MS) and detection of each ON in the negative ionization mode. Copyright © 2011 Elsevier B.V. All rights reserved.

Rotational versus alternating hysteresis losses in nonoriented soft magnetic laminations

NASA Astrophysics Data System (ADS)

Fiorillo, F.; Rietto, A. M.

1993-05-01

Rotational and alternating hysteresis losses have been investigated in theory and experiment in nonoriented soft magnetic laminations. Attention has been focused on the dependence of energy loss on peak magnetization Ip. The experiments, performed in a wide induction range (˜2×10-4 T≤Ip≤˜1.6 T), show that the ratio between rotational and alternating energy losses Whr/Wha is a monotonically decreasing function of Ip. A quantitative theoretical investigation is carried out through modeling of the magnetization process under rotating field and its relation to processes under alternating field. Three basic mechanisms of magnetization rotation are considered: linear combination of unidirectional hysteresis loops at low inductions (Rayleigh region), cyclic rearrangement of magnetic domains between different easy directions at intermediate inductions, and coherent spin rotation toward the approach to magnetic saturation. The ensuing predicted behavior of Whr/Wha is found to be in good agreement with the experiments performed in nonoriented low carbon steel and 3% FeSi laminations.

Enhancing speech recognition using improved particle swarm optimization based hidden Markov model.

PubMed

Selvaraj, Lokesh; Ganesan, Balakrishnan

2014-01-01

Enhancing speech recognition is the primary intention of this work. In this paper a novel speech recognition method based on vector quantization and improved particle swarm optimization (IPSO) is suggested. The suggested methodology contains four stages, namely, (i) denoising, (ii) feature mining (iii), vector quantization, and (iv) IPSO based hidden Markov model (HMM) technique (IP-HMM). At first, the speech signals are denoised using median filter. Next, characteristics such as peak, pitch spectrum, Mel frequency Cepstral coefficients (MFCC), mean, standard deviation, and minimum and maximum of the signal are extorted from the denoised signal. Following that, to accomplish the training process, the extracted characteristics are given to genetic algorithm based codebook generation in vector quantization. The initial populations are created by selecting random code vectors from the training set for the codebooks for the genetic algorithm process and IP-HMM helps in doing the recognition. At this point the creativeness will be done in terms of one of the genetic operation crossovers. The proposed speech recognition technique offers 97.14% accuracy.

The role of distinct parameters of interplanetary shocks in their propagation into and within the Earth's dayside magnetosphere, and their impact on magnetospheric particle populations

NASA Astrophysics Data System (ADS)

Colpitts, C. A.; Cattell, C. A.

2016-12-01

Interplanetary (IP) shocks are abrupt changes in the solar wind velocity and/or magnetic field. When an IP shock impacts the Earth's magnetosphere, it can trigger a number of responses including geomagnetic storms and substorms that affect radiation to satellites and aircraft, and ground currents that disrupt the power grid. There are a wide variety of IP shocks, and they interact with the magnetosphere in different ways depending on their orientation, speed and other factors. The distinct individual characteristics of IP shocks can have a dramatic effect on their impact on the near-earth environment. While some research has been done on the impact of shock parameters on their geo-effectiveness, these studies primarily utilized ground magnetometer derived indices such as Dst, AE and SME or signals at geosynchronous satellites. The current unprecedented satellite coverage of the magnetosphere, particularly on the dayside, presents an opportunity to directly measure how different shocks propagate into and within the magnetosphere, and how they affect the various particle populations therein. Initial case studies reveal that smaller shocks can have unexpected impacts in the dayside magnetosphere, including unusual particle and electric field signatures, depending on shock parameters. We have recently compiled a database of sudden impulses from 2012-2016, and the location of satellites in the dayside magnetosphere at the impulse times. We are currently combining and comparing this with existing databases compiled at UNH, Harvard and others, as well as solar wind data from ACE, Wind and other solar wind monitors, to generate a complete and accurate list of IP shocks, cataloguing parameters such as the type of shock (CME, CIR etc.), strength (Mach number, solar wind velocity etc.) and shock normal angle. We are investigating the magnetospheric response to these shocks using GOES, ARTEMIS and Cluster data, augmented with RBSP and MMS data where available, to determine what effect the various shock parameters have on their propagation through and impact on the magnetosphere. We will present several case studies from our database that show how different parameters affect how shocks propagate in the dayside and how they affect the particles therein.

Combining genomic and proteomic approaches for epigenetics research

PubMed Central

Han, Yumiao; Garcia, Benjamin A

2014-01-01

Epigenetics is the study of changes in gene expression or cellular phenotype that do not change the DNA sequence. In this review, current methods, both genomic and proteomic, associated with epigenetics research are discussed. Among them, chromatin immunoprecipitation (ChIP) followed by sequencing and other ChIP-based techniques are powerful techniques for genome-wide profiling of DNA-binding proteins, histone post-translational modifications or nucleosome positions. However, mass spectrometry-based proteomics is increasingly being used in functional biological studies and has proved to be an indispensable tool to characterize histone modifications, as well as DNA–protein and protein–protein interactions. With the development of genomic and proteomic approaches, combination of ChIP and mass spectrometry has the potential to expand our knowledge of epigenetics research to a higher level. PMID:23895656

Attenuating illusory binding with TMS of the right parietal cortex

PubMed Central

Esterman, Michael; Verstynen, Timothy; Robertson, Lynn C.

2007-01-01

A number of neuroimaging and neuropsychology studies have implicated various regions of parietal cortex as playing a critical role in the binding of color and form into conjunctions. The current study investigates the role of two such regions by examining how parietal transcranial magnetic stimulation (TMS) influences binding errors known as ‘illusory conjunctions.’ Participants made fewer binding errors after 1 Hz rTMS of the right intraparietal sulcus (IPS), while basic perception of features (colors and shape) was unaffected. No perceptual effects were found following left IPS stimulation, or stimulation of the right angular gyrus at the junction of the transverse occipital sulcus (IPS/TOS). These results support a role for the parietal cortex in feature binding but in ways that may require rethinking. PMID:17336097

Modifications of the ionosphere prior to large earthquakes: report from the Ionosphere Precursor Study Group

NASA Astrophysics Data System (ADS)

Oyama, K.-I.; Devi, M.; Ryu, K.; Chen, C. H.; Liu, J. Y.; Liu, H.; Bankov, L.; Kodama, T.

2016-12-01

The current status of ionospheric precursor studies associated with large earthquakes (EQ) is summarized in this report. It is a joint endeavor of the "Ionosphere Precursor Study Task Group," which was formed with the support of the Mitsubishi Foundation in 2014-2015. The group promotes the study of ionosphere precursors (IP) to EQs and aims to prepare for a future EQ dedicated satellite constellation, which is essential to obtain the global morphology of IPs and hence demonstrate whether the ionosphere can be used for short-term EQ predictions. Following a review of the recent IP studies, the problems and specific research areas that emerged from the one-year project are described. Planned or launched satellite missions dedicated (or suitable) for EQ studies are also mentioned.

Seasonal and life-phase related differences in growth in Scarus ferrugineus on a southern Red Sea fringing reef.

PubMed

Afeworki, Y; Videler, J J; Berhane, Y H; Bruggemann, J H

2014-05-01

Temporal trends in growth of the rusty parrotfish Scarus ferrugineus were studied on a southern Red Sea fringing reef that experiences seasonal changes in environmental conditions and benthic algal resources. Length increment data from tagging and recapture were compared among periods and sexes and modelled using GROTAG, a von Bertalanffy growth model. The growth pattern of S. ferrugineus was highly seasonal with a maximum occurring between April and June and a minimum between December and March. Body condition followed the seasonal variation in growth, increasing from April to June and decreasing from December to March. The season of maximum growth coincided with high irradiation, temperature increases and peak abundance of the primary food source, the epilithic algal community. There was a decline in growth rate during summer (July to October) associated with a combination of extreme temperatures and lowered food availability. There were strong sexual size dimorphism (SSD) and life-history traits. Terminal-phase (TP) males achieved larger asymptotic lengths than initial-phase individuals (IP) (L(∞) 34·55 v. 25·12 cm) with growth coefficients (K) of 0·26 and 0·38. The TPs were growing four times as fast as IPs of similar size. Three individuals changed from IP to TP while at liberty and grew eight times faster than IPs of similar size, suggesting that sex change in S. ferrugineus is accompanied by a surge in growth rate. The SSD in S. ferrugineus thus coincided with fast growth that started during sex change and continued into the TP. Faster growth during sex change suggests that the cost associated with sex change is limited. © 2014 The Fisheries Society of the British Isles.

Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, alpha(1)- and 5-HT(2A)-receptors.

PubMed

Sebban, Claude; Tesolin-Decros, Brigitte; Ciprian-Ollivier, Jorge; Perret, Laurent; Spedding, Michael

2002-01-01

1. The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0 - 30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1 - 3 mg kg(-1) s.c.) caused a marked dose-dependent increase in EEG power in the frontal cortex at 1 - 3 Hz with decreases in power at higher frequencies (9 - 30 Hz). At high doses (3 mg kg(-1) s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05 - 0.1 mg kg(-1) i.p.) caused similar effects but with lesser changes in power. 2. In contrast, the non-competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1 - 10 mg kg(-1) i.p.). The atypical antipsychotic clozapine (0.2 mg kg(-1) s.c.) synchronized the EEG (peak 8 Hz). The 5-HT(2A)-antagonist, M100907, specifically increased EEG power at 2 - 3 Hz at low doses (10 and 50 microg kg(-1) s.c.), whereas at higher doses (0.1 mg kg(-1) s.c.) the profile resembled that of clozapine. 3. Clozapine (0.2 mg kg(-1) s.c. ), GYKI 53655 (5 mg kg(-1) i.p.), prazosin (0.05 and 0.1 mg kg(-1) i.p.), and M100907 (0.01 and 0.05 mg kg(-1) s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg(-1) s.c.), but not the increase in power at 1 - 3 Hz in prefrontal cortex.

Current responsive devices for synchronous generators

DOEpatents

Karlicek, R.F.

1983-09-27

A device for detecting current imbalance between phases of a polyphase alternating current generator. A detector responds to the maximum peak current in the generator, and detecting means generates an output for each phase proportional to the peak current of each phase. Comparing means generates an output when the maximum peak current exceeds the phase peak current. 11 figs.

Non-solenoidal Startup with High-Field-Side Local Helicity Injection on the Pegasus ST

NASA Astrophysics Data System (ADS)

Perry, J. M.; Bodner, G. M.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Pachicano, J. L.; Pierren, C.; Richner, N. J.; Rodriguez Sanchez, C.; Schlossberg, D. J.; Reusch, J. A.; Weberski, J. D.

2017-10-01

Local Helicity Injection (LHI) is a non-solenoidal startup technique utilizing electron current injectors at the plasma edge to initiate a tokamak-like plasma at high Ip . Recent experiments on Pegasus explore the inherent tradeoffs between high-field-side (HFS) injection in the lower divertor region and low-field-side (LFS) injection at the outboard midplane. Trade-offs include the relative current drive contributions of HI and poloidal induction, and the magnetic geometry required for relaxation to a tokamak-like state. HFS injection using a set of two increased-area injectors (Ainj = 4 cm2, Vinj 1.5 kV, and Iinj 8 kA) in the lower divertor is demonstrated over the full range of toroidal field available on Pegasus (BT 0 <= 0.15 T). Increased PMI on both the injectors and the lower divertor plates was observed during HFS injection, and was substantively mitigated through optimization of injector geometry and placement of local limiters to reduce scrape-off density in the divertor region. Ip up to 200 kA is achieved with LHI as the dominant current drive, consistent with expectations from helicity balance. To date, experiments support Ip increasing linearly with helicity injection rate. The high normalized current (IN >= 10) attainable with LHI and the favorable stability of the ultra-low aspect ratio, low-li LHI-driven plasmas allow access to high βt-up to 100 % , as indicated by kinetically-constrained equilibrium reconstructions. Work supported by US DOE Grant DE-FG02-96ER54375.

MST's Programmable Power Supplies: Bt Update, Bp Prototype

NASA Astrophysics Data System (ADS)

Holly, D. J.; Chapman, B. E.; McCollam, K. J.; Morin, J. C.; Thomas, M. A.

2013-10-01

MST's toroidal field programmable power supply (Bt PPS) has now been in operation for several years and has provided important new capabilities. One of the primary goals for the Bt PPS is the partial optimization of inductive current profile control, involving control of the poloidal electric field. The Bt PPS has achieved fluctuation reduction over MST's entire range of Ip. At the largest Ip, the Bt PPS achieves fluctuation reduction with a smaller poloidal electric field than the previous passive system, implying that substantially longer periods of current profile control may be possible. The Bt PPS has also been used to produce Ohmic tokamak plasmas in MST. With an applied toroidal field of 0.135 T, and q(a) > 2, the estimated energy confinement time is roughly consistent with neo-Alcator scaling. Driving q(a) < 2 with larger Ip, the confinement time degrades, but the discharge duration does not terminate prematurely. To fully optimize current profile control and to test MST operational limits, a PPS is also needed for the Bp circuit. Currently in prototype stage, the Bp PPS will feature a number of innovations to increase its flexibility and performance. Isolated charging, control, and monitor systems will eliminate charging relays, reduce coupling between modules, and minimize capacitor heating. Seven-level pulse width modulation will reduce output ripple and switching losses. Solid state shorting bars will eliminate shorting relays and minimize wiring. A balanced switching algorithm will minimize capacitive noise generation. Work supported by U. S. D. o. E.

How Interplanetary Scintillation Data Can Improve Modeling of Coronal Mass Ejection Propagation

NASA Astrophysics Data System (ADS)

Taktakishvili, A.; Mays, M. L.; Manoharan, P. K.; Rastaetter, L.; Kuznetsova, M. M.

2017-12-01

Coronal mass ejections (CMEs) can have a significant impact on the Earth's magnetosphere-ionosphere system and cause widespread anomalies for satellites from geosynchronous to low-Earth orbit and produce effects such as geomagnetically induced currents. At the NASA/GSFC Community Coordinated Modeling Center we have been using ensemble modeling of CMEs since 2012. In this presnetation we demonstrate that using of interplanetary scintillation (IPS) observations from the Ooty Radio Telescope facility in India can help to track CME propagaion and improve ensemble forecasting of CMEs. The observations of the solar wind density and velocity using IPS from hundreds of distant sources in ensemble modeling of CMEs can be a game-changing improvement of the current state of the art in CME forecasting.

Key technologies and concepts for beyond-3G networks

NASA Astrophysics Data System (ADS)

Pehkonen, Kari; Uskela, Sami; Kalliojarvi, Kari; Oksanen, Lauri; Rikkinen, Kari

2001-10-01

Standardization of 3rd Generation (3G) mobile communication systems has produced the first specification releases and the commercial deployment of the 3G systems has started. Whereas 1G and 2G focused on efficiently providing voice services, in 3G a lot of attention has been devoted to solutions that support both Circuit Switched (CS) and Packet Switched (PS) communication. That has called for very flexible air interface and network solutions. 3G will continue to evolve and there are already on-going standardization activities that will, for example, boost the peak data rates up to 5-10 Mbps and improve spectral efficiency by 2-4 times. In the future, 3G evolution will be going towards 10/100 Mbps peak data rates in wide/local are coverage, respectively. This will take place partly because of technical improvements of 3G radio interface solutions, but also due to network evolution which will allow the integration other radio access methods like radio LANs into the 3G system. In longer term the 3G network evolution will be going towards ALL-IP networks. As 3G evolution seems to be going towards 10 Mbps/100 Mbps peak data rates and ALL-IP networks any beyond 3G air interface or network solution should be clearly better in order to justify its technical and commercial feasibility. Given the long evolution time of 3G and integration of other radio access schemes with 3G radio we may not even see a new, complete beyond 3G system being developed. Maybe we will just witness the emergence of a new, more advanced radio access solution which will then be connected to the evolving 3G network. As 3G evolution will continue for several years to come the research targets for any beyond 3G solutions must be set very high. When it comes to air interface, we should aim at 100 Mbps peak data rates for wide area access with high mobility, and at 1 Gbps for local area access with low mobility. Regarding possible commercial launches of any beyond 3G systems or solutions they could then take place around year 2010 or even later.

The weakening effect of soluble epoxide hydrolase inhibitor AUDA on febrile response to lipopolysaccharide and turpentine in rat.

PubMed

Piotrowski, Jakub; Jędrzejewski, Tomasz; Pawlikowska, Małgorzata; Pacuła, Agata Joanna; Ścianowski, Jacek; Kozak, Wiesław

2017-11-01

A still growing body of evidence suggests the importance of epoxyeicosatrienoic acids (EETs) in the regulation of inflammatory response; therefore, drugs that stabilize their levels by targeting the soluble epoxide hydrolase (sEH), an enzyme responsible for their metabolism, are currently under investigation. The effect of sEH inhibitors on molecular components of fever mechanism, i.e., on synthesis of pro-inflammatory cytokines or prostaglandins, has been repeatedly proven; however, the hypothesis that sEH inhibitors affect febrile response has never been tested. The aim of this study was to examine if sEH inhibition affects core body temperature (Tb) as well as Tb changes during febrile response to infectious (lipopolysaccharide; LPS) or non-infectious (turpentine; TRP) stimuli. Male Wistar rats were implanted intra-abdominally with miniature biotelemeters to monitor Tb. A potent sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) was suspended in olive oil and administrated into animals in the intraperitoneal (i.p.) dose of 15 mg/kg, which, as we showed, has no significant influence on normal Tb. We have found that AUDA injected 3 h after LPS (50 μg/kg i.p.) significantly weakened febrile rise of Tb. Moreover, injection of sEH inhibitor 7 h after turpentine (administrated subcutaneously in a dose of 100 μL/rat) markedly reduced the peak period of aseptic fever. Obtained results provide first experimental evidence that sEH inhibitors possess anti-pyretic properties. Therefore, medicines targeting sEH enzymatic activity should be considered as a complement to the arsenal of topical medications used to treat fever especially in clinical situations when non-steroidal anti-inflammatory drugs are ineffective.

Development of a sequential injection-square wave voltammetry method for determination of paraquat in water samples employing the hanging mercury drop electrode.

PubMed

dos Santos, Luciana B O; Infante, Carlos M C; Masini, Jorge C

2010-03-01

This work describes the development and optimization of a sequential injection method to automate the determination of paraquat by square-wave voltammetry employing a hanging mercury drop electrode. Automation by sequential injection enhanced the sampling throughput, improving the sensitivity and precision of the measurements as a consequence of the highly reproducible and efficient conditions of mass transport of the analyte toward the electrode surface. For instance, 212 analyses can be made per hour if the sample/standard solution is prepared off-line and the sequential injection system is used just to inject the solution towards the flow cell. In-line sample conditioning reduces the sampling frequency to 44 h(-1). Experiments were performed in 0.10 M NaCl, which was the carrier solution, using a frequency of 200 Hz, a pulse height of 25 mV, a potential step of 2 mV, and a flow rate of 100 µL s(-1). For a concentration range between 0.010 and 0.25 mg L(-1), the current (i(p), µA) read at the potential corresponding to the peak maximum fitted the following linear equation with the paraquat concentration (mg L(-1)): i(p) = (-20.5 ± 0.3)C (paraquat) - (0.02 ± 0.03). The limits of detection and quantification were 2.0 and 7.0 µg L(-1), respectively. The accuracy of the method was evaluated by recovery studies using spiked water samples that were also analyzed by molecular absorption spectrophotometry after reduction of paraquat with sodium dithionite in an alkaline medium. No evidence of statistically significant differences between the two methods was observed at the 95% confidence level.

Distinct p53 genomic binding patterns in normal and cancer-derived human cells

PubMed Central

McCorkle, Sean R; McCombie, WR; Dunn, John J

2011-01-01

Here, we report genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIP-seq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells. PMID:22127205

Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells

PubMed Central

Mungenast, Alison E.; Siegert, Sandra; Tsai, Li-Huei

2018-01-01

In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer’s disease (AD) have been often failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells. In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD. PMID:26657644

Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells.

PubMed

Mungenast, Alison E; Siegert, Sandra; Tsai, Li-Huei

2016-06-01

In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells. In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas9 will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Imperatoxin a enhances Ca(2+) release in developing skeletal muscle containing ryanodine receptor type 3.

PubMed Central

Nabhani, Thomas; Zhu, Xinsheng; Simeoni, Ilenia; Sorrentino, Vincenzo; Valdivia, Héctor H; García, Jesús

2002-01-01

Most adult mammalian skeletal muscles contain only one isoform of ryanodine receptor (RyR1), whereas neonatal muscles contain two isoforms (RyR1 and RyR3). Membrane depolarization fails to evoke calcium release in muscle cells lacking RyR1, demonstrating an essential role for this isoform in excitation-contraction coupling. In contrast, the role of RyR3 is unknown. We studied the participation of RyR3 in calcium release in wild type (containing both RyR1 and RyR3 isoforms) and RyR3-/- (containing only RyR1) myotubes in the presence or absence of imperatoxin A (IpTxa), a high-affinity agonist of ryanodine receptors. IpTxa significantly increased the amplitude and the rate of release only in wild-type myotubes. Calcium currents, recorded simultaneously with the transients, were not altered with IpTxa treatment. [(3)H]ryanodine binding to RyR1 or RyR3 was significantly increased in the presence of IpTxa. Additionally, IpTxa modified the gating and conductance level of single RyR1 or RyR3 channels when studied in lipid bilayers. Our data show that IpTxa can interact with both RyRs and that RyR3 is functional in myotubes and it can amplify the calcium release signal initiated by RyR1, perhaps through a calcium-induced mechanism. In addition, our data indicate that when RyR3-/- myotubes are voltage-clamped, the effect of IpTxa is not detected because RyR1s are under the control of the dihydropyridine receptor. PMID:11867448

Improvement of the course “Management of intellectual property” based on the mixed state contract in the field of scientific R&D

NASA Astrophysics Data System (ADS)

Yakovlev, D.; Ageev, A.; Yushkov, E.; Bogatyreova, M.

2017-01-01

Intellectual property (IP) is one of the forms of storing knowledge - intangible assets of knowledge economy. The translation of IP knowledge to the young generation is one of the challenges of nuclear knowledge management. At the NRNU MEPhI (National Research Nuclear University MEPhI), the subject is studied within the framework of the academic course “Management of intellectual property. The aim of the course is to train qualified specialists, ready to use modern methods of strategic management of IP in commercial firms. The article is devoted to the strengthening and transfer of IP rights for scientific output application in industry and commerce. The state remains the main source that finances all the significant developments in the field of science and technology. Therefore, the primary task is to effectively utilize the R&D output created at the expense of the Federal budget, both within the state order and the estimated budget financing. Currently, there exist contradictions in the area of strengthening and transfer of rights for R&D in the field of science. The newly borne concept dealing with the strengthening of IP rights for the scientific R&D output, centers on the theory of a mixed state contract and is conveniently integrated with the academic course mentioned. Knowledge itself takes the form of IP, as soon as it becomes formalized. The academic course when supplemented with various approaches to strengthening and transfer of IP rights for the scientific R&D output certainly gives a better understanding of the commercialization process of the intellectual capital and structures relevance to intellectual property. The research material is integrated with the educational process, and the academic course “Management of intellectual property” is designed both for economic and engineering specialties.

Epigenetic rejuvenation.

PubMed

Manukyan, Maria; Singh, Prim B

2012-05-01

Induced pluripotent stem (iPS) cells have provided a rational means of obtaining histo-compatible tissues for 'patient-specific' regenerative therapies (Hanna et al. 2010; Yamanaka & Blau 2010). Despite the obvious potential of iPS cell-based therapies, there are certain problems that must be overcome before these therapies can become safe and routine (Ohi et al. 2011; Pera 2011). As an alternative, we have recently explored the possibility of using 'epigenetic rejuvenation', where the specialized functions of an old cell are rejuvenated in the absence of any change in its differentiated state (Singh & Zacouto 2010). The mechanism(s) that underpin 'epigenetic rejuvenation' are unknown and here we discuss model systems, using key epigenetic modifiers, which might shed light on the processes involved. Epigenetic rejuvenation has advantages over iPS cell techniques that are currently being pursued. First, the genetic and epigenetic abnormalities that arise through the cycle of dedifferentiation of somatic cells to iPS cells followed by redifferentiation of iPS cells into the desired cell type are avoided (Gore et al. 2011; Hussein et al. 2011; Pera 2011): epigenetic rejuvenation does not require passage through the de-/redifferentiation cycle. Second, because the aim of epigenetic rejuvenation is to ensure that the differentiated cell type retains its specialized function it makes redundant the question of transcriptional memory that is inimical to iPS cell-based therapies (Ohi et al. 2011). Third, to produce unrelated cell types using the iPS technology takes a long time, around three weeks, whereas epigenetic rejuvenation of old cells will take only a matter of days. Epigenetic rejuvenation provides the most safe, rapid and cheap route to successful regenerative medicine. © 2012 The Authors. Journal compilation © 2012 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

Maternal Attributions of Infant Behavior and Parenting in Toddlerhood Predict Teacher-Rated Internalizing Problems in Childhood.

PubMed

Wagner, Nicholas J; Gueron-Sela, Noa; Bedford, Rachael; Propper, Cathi

2018-06-12

Social-information-processing theories of parenting posit that parents' beliefs and attributions about their children's behaviors contribute to how parents interact with their children. The purpose of this study was to examine the associations between negative parenting attributions in infancy, harsh-intrusive parenting in toddlerhood, and children's internalizing problems (IPs) in early childhood. Using data from a diverse longitudinal study (n = 206), the current study used a structural equation modeling approach to test if mothers' negative attributions measured at 6 months predicted teacher ratings of children's IPs in 1st grade, as well as the extent to which observed harsh-intrusive parenting behaviors measured at ages 1, 2, and 3 years mediated this link. Maternal negative attributions in infancy predict more IPs in 1st grade, but this link becomes nonsignificant when observed harsh-intrusive parenting is included as a mediator. A significant indirect effect suggests that harsh-intrusive parenting mediates the association between early negative attributions and eventual IPs. Findings from this study identify harsh-intrusive parenting behaviors as one potential mechanism through which the effects of early attributions are carried forward to influence children's IPs. The developmental and clinical implications of these findings are discussed.

Maximizing MST's inductive capability with a Bp programmable power supply

NASA Astrophysics Data System (ADS)

Chapman, B. E.; Holly, D. J.; Jacobson, C. M.; McCollam, K. J.; Morin, J. C.; Sarff, J. S.; Squitieri, A.

2016-10-01

A major goal of the MST program is the advancement of inductive control for the development of both the RFP's fusion potential and, synergistically, the predictive capability of fusion science. This entails programmable power supplies (PPS's) for the Bt and Bp circuits. A Bt PPS is already in place, allowing advanced RFP operation and the production of tokamak plasmas, and a Bp PPS prototype is under construction. To explore some of the new capabilities to be provided by the Bp PPS, the existing Bt PPS has been temporarily connected to the Bp circuit. One key result is new-found access to very low Ip (20 kA) and very low Lundquist number, S (104). At this low S, simulation of RFP plasmas with the MHD code NIMROD is readily achievable, and work toward validation of extended MHD models using NIMROD is underway with direct comparisons to these MST plasmas. The full Bp PPS will also provide higher Ip and S than presently possible, allowing MST to produce plasmas with S spanning as much as five orders of magnitude, a dramatic extension of MST's capability. In these initial tests, the PPS has also increased five-fold MST's Ip flattop duration, to about 100 ms. This, coupled with the recently demonstrated PPS ability to drive large-amplitude sinusoidal oscillations in Ip, will allow tests of extended-duration oscillating field current drive, the goal of which is ac sustainment of a quasi-dc plasma current. Work supported by US DOE.

Provocative tests of parathyroid and C cell function in adrenalectomized and chemically sympathectomized rats.

PubMed

Heath, H

1980-10-01

Recent in vitro and in vivo evidence shows that secretion of parathyroid hormone (PTH) and calcitonin (CT) is stimulated by beta-adrenergic agonists and inhibited by beta-adrenergic antagonists. To assess the possible roles of adrenal medullary or adrenergic nerve terminal catecholamines in calcium homeostasis, we have examined serum calcium (Ca), immunoreactive PTH (iPTH), and immunoreactive CT (iCT) in control, adrenalectomized (ADRX), and chemically sympathectomized [6-hydroxydopamine (6-OHDA)] rats. Animals were studied in the fed and fasted states, after ip injection of CA and after ip injection of EDTA. In comparison with fasted rats, fed control rats tended to have increased serum Ca and iCT, but decreased or unchanged iPTH. Neither adrenalectomy nor 6-OHDA treatment notably altered this pattern. Serum iCT concentrations rose markedly after ip Ca, and peak iCT responses remained normal in ADRX and 6-OHDA-treated rats. Similarly, rises of iPTH levels after EDTA-induced hypocalcemia were normal in ADRX and 6-OHDA-treated rats. The only possible abnormality concerned basal serum iCT levels after 6-OHDA treatment, which were lower than control in five of six experiments, albeit not always significantly. We conclude that deprivation of either adrenal medullary or adrenergic nerve terminal catecholamines does not interfere with plasma Ca regulation or the homeostatic responses of PTH and CT in the rat.

HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis.

PubMed

Kulakovskiy, Ivan V; Vorontsov, Ilya E; Yevshin, Ivan S; Sharipov, Ruslan N; Fedorova, Alla D; Rumynskiy, Eugene I; Medvedeva, Yulia A; Magana-Mora, Arturo; Bajic, Vladimir B; Papatsenko, Dmitry A; Kolpakov, Fedor A; Makeev, Vsevolod J

2018-01-04

We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco11. In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, http://molotool.autosome.ru) that applies HOCOMOCO models for visualization of binding sites in short DNA sequences. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Multiple current peaks in room-temperature atmospheric pressure homogenous dielectric barrier discharge plasma excited by high-voltage tunable nanosecond pulse in air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, De-Zheng; Wang, Wen-Chun; Zhang, Shuai

2013-05-13

Room temperature homogenous dielectric barrier discharge plasma with high instantaneous energy efficiency is acquired by using nanosecond pulse voltage with 20-200 ns tunable pulse width. Increasing the voltage pulse width can lead to the generation of regular and stable multiple current peaks in each discharge sequence. When the voltage pulse width is 200 ns, more than 5 organized current peaks can be observed under 26 kV peak voltage. Investigation also shows that the organized multiple current peaks only appear in homogenous discharge mode. When the discharge is filament mode, organized multiple current peaks are replaced by chaotic filament current peaks.

Reductions in the Cardiac Transient Outward K+ Current Ito Caused by Chronic β-Adrenergic Receptor Stimulation Are Partly Rescued by Inhibition of Nuclear Factor κB.

PubMed

Panama, Brian K; Korogyi, Adam S; Aschar-Sobbi, Roozbeh; Oh, Yena; Gray, Charles B B; Gang, Hongying; Brown, Joan Heller; Kirshenbaum, Lorrie A; Backx, Peter H

2016-02-19

The fast transient outward potassium current (Ito,f) plays a critical role in the electrical and contractile properties of the myocardium. Ito,f channels are formed by the co-assembly of the pore-forming α-subunits, Kv4.2 and Kv4.3, together with the accessory β-subunit KChIP2. Reductions of Ito,f are common in the diseased heart, which is also associated with enhanced stimulation of β-adrenergic receptors (β-ARs). We used cultured neonatal rat ventricular myocytes to examine how chronic β-AR stimulation decreases Ito,f. To determine which downstream pathways mediate these Ito,f changes, adenoviral infections were used to inhibit CaMKIIδc, CaMKIIδb, calcineurin, or nuclear factor κB (NF-κB). We observed that chronic β-AR stimulation with isoproterenol (ISO) for 48 h reduced Ito,f along with mRNA expression of all three of its subunits (Kv4.2, Kv4.3, and KChIP2). Inhibiting either CaMKIIδc nor CaMKIIδb did not prevent the ISO-mediated Ito,f reductions, even though CaMKIIδc and CaMKIIδb clearly regulated Ito,f and the mRNA expression of its subunits. Likewise, calcineurin inhibition did not prevent the Ito,f reductions induced by β-AR stimulation despite strongly modulating Ito,f and subunit mRNA expression. In contrast, NF-κB inhibition partly rescued the ISO-mediated Ito,f reductions in association with restoration of KChIP2 mRNA expression. Consistent with these observations, KChIP2 promoter activity was reduced by p65 as well as β-AR stimulation. In conclusion, NF-κB, and not CaMKIIδ or calcineurin, partly mediates the Ito,f reductions induced by chronic β-AR stimulation. Both mRNA and KChIP2 promoter data suggest that the ISO-induced Ito,f reductions are, in part, mediated through reduced KChIP2 transcription caused by NF-κB activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Doubling the Spectrum of Time-Domain Induced Polarization: Removal of Harmonic Noise and Self-Potential Drift

NASA Astrophysics Data System (ADS)

Fiandaca, G.; Olsson, P. I.; Auken, E.; Larsen, J. J.; Maurya, P. K.; Dahlin, T.

2015-12-01

The extraction of spectral information in the inversion process of time-domain (TD) induced polarization (IP) data is changing the use of the IP method. Data interpretation is evolving from a qualitative description of the soil, able only to discriminate the presence of contrasts in chargeability parameters, towards a quantitative analysis of the investigated media, which allows soil-type characterization. Two major limitations restrict the extraction of the spectral information of TDIP data in the field: i) the difficulty of acquiring reliable early-time measurements, in the millisecond range and ii) the self-potential drift in the measured potentials distorting the shape of the late time IP decays, in the second range. For measuring at early-times, we developed a new method for removing the powerline noise contained in the data through a model-based approach, localizing the fundamental frequency of the powerline signal in the full-waveform IP recordings. By this, we cancel both the fundamental signal and its harmonics. This noise cancellation allows the use of earlier and narrower gates, down to a few milliseconds after the current turn-off. Even earlier gates can be measured but they will be inductively "contaminated" which we at present want to avoid. A proper removal of the self-potential drift present between the potential electrodes is essential for preserving the shape of the TD decays, especially for late times. Usually constant or linear drift-removal algorithms are used, but these algorithms fail in removing the background potentials due to the polarization of the electrodes previously used for current injection. We developed a drift-removal scheme that model the polarization effect and efficiently allows for preserving the shape of the IP decays. The removal of both the harmonic noise and self-potential drift allows for doubling the usable range of TDIP data to more than three decades in time (corresponding to three decays in frequency), and will significantly advance the science and the applicability of the IP method in exploration and environmental geophysics.

Experiments and Simulations on Magnetically Driven Implosions in High Repetition Rate Dense Plasma Focus

NASA Astrophysics Data System (ADS)

Caballero Bendixsen, Luis; Bott-Suzuki, Simon; Cordaro, Samuel; Krishnan, Mahadevan; Chapman, Stephen; Coleman, Phil; Chittenden, Jeremy

2015-11-01

Results will be shown on coordinated experiments and MHD simulations on magnetically driven implosions, with an emphasis on current diffusion and heat transport. Experiments are run at a Mather-type dense plasma focus (DPF-3, Vc: 20 kV, Ip: 480 kA, E: 5.8 kJ). Typical experiments are run at 300 kA and 0.33 Hz repetition rate with different gas loads (Ar, Ne, and He) at pressures of ~ 1-3 Torr, usually gathering 1000 shots per day. Simulations are run at a 96-core HP blade server cluster using 3GHz processors with 4GB RAM per node.Preliminary results show axial and radial phase plasma sheath velocity of ~ 1x105 m/s. These are in agreement with the snow-plough model of DPFs. Peak magnetic field of ~ 1 Tesla in the radial compression phase are measured. Electron densities on the order of 1018 cm-3 anticipated. Comparison between 2D and 3D models with empirical results show a good agreement in the axial and radial phase.

Modelling and multi objective optimization of WEDM of commercially Monel super alloy using evolutionary algorithms

NASA Astrophysics Data System (ADS)

Varun, Sajja; Reddy, Kalakada Bhargav Bal; Vardhan Reddy, R. R. Vishnu

2016-09-01

In this research work, development of a multi response optimization technique has been undertaken, using traditional desirability analysis and non-traditional particle swarm optimization techniques (for different customer's priorities) in wire electrical discharge machining (WEDM). Monel 400 has been selected as work material for experimentation. The effect of key process parameters such as pulse on time (TON), pulse off time (TOFF), peak current (IP), wire feed (WF) were on material removal rate (MRR) and surface roughness(SR) in WEDM operation were investigated. Further, the responses such as MRR and SR were modelled empirically through regression analysis. The developed models can be used by the machinists to predict the MRR and SR over a wide range of input parameters. The optimization of multiple responses has been done for satisfying the priorities of multiple users by using Taguchi-desirability function method and particle swarm optimization technique. The analysis of variance (ANOVA) is also applied to investigate the effect of influential parameters. Finally, the confirmation experiments were conducted for the optimal set of machining parameters, and the betterment has been proved.

Akt/PKB activation and insulin signaling: a novel insulin signaling pathway in the treatment of type 2 diabetes.

PubMed

Mackenzie, Richard Wa; Elliott, Bradley T

2014-01-01

Type 2 diabetes is a metabolic disease categorized primarily by reduced insulin sensitivity, β-cell dysfunction, and elevated hepatic glucose production. Treatments reducing hyperglycemia and the secondary complications that result from these dysfunctions are being sought after. Two distinct pathways encourage glucose transport activity in skeletal muscle, ie, the contraction-stimulated pathway reliant on Ca(2+)/5'-monophosphate-activated protein kinase (AMPK)-dependent mechanisms and an insulin-dependent pathway activated via upregulation of serine/threonine protein kinase Akt/PKB. Metformin is an established treatment for type 2 diabetes due to its ability to increase peripheral glucose uptake while reducing hepatic glucose production in an AMPK-dependent manner. Peripheral insulin action is reduced in type 2 diabetics whereas AMPK signaling remains largely intact. This paper firstly reviews AMPK and its role in glucose uptake and then focuses on a novel mechanism known to operate via an insulin-dependent pathway. Inositol hexakisphosphate (IP6) kinase 1 (IP6K1) produces a pyrophosphate group at the position of IP6 to generate a further inositol pyrophosphate, ie, diphosphoinositol pentakisphosphate (IP7). IP7 binds with Akt/PKB at its pleckstrin homology domain, preventing interaction with phosphatidylinositol 3,4,5-trisphosphate, and therefore reducing Akt/PKB membrane translocation and insulin-stimulated glucose uptake. Novel evidence suggesting a reduction in IP7 production via IP6K1 inhibition represents an exciting therapeutic avenue in the treatment of insulin resistance. Metformin-induced activation of AMPK is a key current intervention in the management of type 2 diabetes. However, this treatment does not seem to improve peripheral insulin resistance. In light of this evidence, we suggest that inhibition of IP6K1 may increase insulin sensitivity and provide a novel research direction in the treatment of insulin resistance.

Chromatin analyses of Zymoseptoria tritici: Methods for chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq).

PubMed

Soyer, Jessica L; Möller, Mareike; Schotanus, Klaas; Connolly, Lanelle R; Galazka, Jonathan M; Freitag, Michael; Stukenbrock, Eva H

2015-06-01

The presence or absence of specific transcription factors, chromatin remodeling machineries, chromatin modification enzymes, post-translational histone modifications and histone variants all play crucial roles in the regulation of pathogenicity genes. Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) provides an important tool to study genome-wide protein-DNA interactions to help understand gene regulation in the context of native chromatin. ChIP-seq is a convenient in vivo technique to identify, map and characterize occupancy of specific DNA fragments with proteins against which specific antibodies exist or which can be epitope-tagged in vivo. We optimized existing ChIP protocols for use in the wheat pathogen Zymoseptoria tritici and closely related sister species. Here, we provide a detailed method, underscoring which aspects of the technique are organism-specific. Library preparation for Illumina sequencing is described, as this is currently the most widely used ChIP-seq method. One approach for the analysis and visualization of representative sequence is described; improved tools for these analyses are constantly being developed. Using ChIP-seq with antibodies against H3K4me2, which is considered a mark for euchromatin or H3K9me3 and H3K27me3, which are considered marks for heterochromatin, the overall distribution of euchromatin and heterochromatin in the genome of Z. tritici can be determined. Our ChIP-seq protocol was also successfully applied to Z. tritici strains with high levels of melanization or aberrant colony morphology, and to different species of the genus (Z. ardabiliae and Z. pseudotritici), suggesting that our technique is robust. The methods described here provide a powerful framework to study new aspects of chromatin biology and gene regulation in this prominent wheat pathogen. Copyright © 2015 Elsevier Inc. All rights reserved.

DIVERSITY in binding, regulation, and evolution revealed from high-throughput ChIP.

PubMed

Mitra, Sneha; Biswas, Anushua; Narlikar, Leelavati

2018-04-01

Genome-wide in vivo protein-DNA interactions are routinely mapped using high-throughput chromatin immunoprecipitation (ChIP). ChIP-reported regions are typically investigated for enriched sequence-motifs, which are likely to model the DNA-binding specificity of the profiled protein and/or of co-occurring proteins. However, simple enrichment analyses can miss insights into the binding-activity of the protein. Note that ChIP reports regions making direct contact with the protein as well as those binding through intermediaries. For example, consider a ChIP experiment targeting protein X, which binds DNA at its cognate sites, but simultaneously interacts with four other proteins. Each of these proteins also binds to its own specific cognate sites along distant parts of the genome, a scenario consistent with the current view of transcriptional hubs and chromatin loops. Since ChIP will pull down all X-associated regions, the final reported data will be a union of five distinct sets of regions, each containing binding sites of one of the five proteins, respectively. Characterizing all five different motifs and the corresponding sets is important to interpret the ChIP experiment and ultimately, the role of X in regulation. We present diversity which attempts exactly this: it partitions the data so that each partition can be characterized with its own de novo motif. Diversity uses a Bayesian approach to identify the optimal number of motifs and the associated partitions, which together explain the entire dataset. This is in contrast to standard motif finders, which report motifs individually enriched in the data, but do not necessarily explain all reported regions. We show that the different motifs and associated regions identified by diversity give insights into the various complexes that may be forming along the chromatin, something that has so far not been attempted from ChIP data. Webserver at http://diversity.ncl.res.in/; standalone (Mac OS X/Linux) from https://github.com/NarlikarLab/DIVERSITY/releases/tag/v1.0.0.

Evaluation of the effect of jobelyn(®) on chemoconvulsants-induced seizure in mice.

PubMed

Umukoro, Solomon; Omogbiya, Itivere Adrian; Eduviere, Anthony Taghogho

2013-01-01

Epilepsy is a common central nervous system (CNS) disorder characterized by seizures resulting from episodic neuronal discharges. The incidence of toxicity and refractoriness has compromised the clinical efficacy of the drugs currently used for the treatment of convulsions. Thus, there is a need to search for new medicines from plant origin that are readily available and safer for the control of seizures. Jobelyn(®) (JB) is a unique African polyherbal preparation used by the natives to treat seizures in children. This investigation was carried out to evaluate whether JB has anti-seizure property in mice. The animals received JB (5, 10 and 20 mg/kg, p.o) 30 min before induction of convulsions with intraperitoneal (i.p.) injection of picotoxin (6 mg/kg), strychnine (2 mg/kg) and pentylenetetrazole (85 mg/kg) respectively. Diazepam (2 mg/kg, p.o.) was used as the reference drug. Anti-seizure activities were assessed based on the ability of test drugs to prevent convulsions, death or to delay the onset of seizures in mice. JB (5, 10 and 20 mg/kg, p.o) could only delay the onset of seizures induced by pentylenetetrazole (85 mg/kg, i.p.) in mice. However, it did not did not offer any protection against seizure episodes, as it failed to prevent the animals, from exhibiting tonic-clonic convulsions caused by pentylenetetrazole (85 mg/kg, i.p.), strychnine (2 mg/kg) or picrotoxin (6 mg/kg, i.p.). On the other hand, diazepam (2 mg/kg, i.p.), offered 100% protection against convulsive seizures, induced by pentylenetetrazole (85 mg/kg, i.p.). However, it failed to prevent seizures produced by strychnine (2 mg/kg, i.p.) or picrotoxin (6 mg/kg, i.p.). Our results suggest that JB could not prevent the examined chemoconvulsants-induced convulsions. However, its ability to delay the latency to seizures induced by pentylenetetrazole suggests that JB might be effective in the control of the seizure spread in epileptic brains.

Immunohistochemical localization of DPP10 in rat brain supports the existence of a Kv4/KChIP/DPPL ternary complex in neurons.

PubMed

Wang, Wan-Chen; Cheng, Chau-Fu; Tsaur, Meei-Ling

2015-03-01

Subthreshold A-type K(+) currents (ISA s) have been recorded from the cell bodies of hippocampal and neocortical interneurons as well as neocortical pyramidal neurons. Kv4 channels are responsible for the somatodendritic ISA s. It has been proposed that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits, K(+) channel-interacting proteins (KChIPs), and dipeptidyl peptidase-like proteins (DPPLs). However, colocalization evidence was still lacking. The distribution of DPP10 mRNA in rodent brain has been reported but its protein localization remains unknown. In this study, we generated a DPP10 antibody to label DPP10 protein in adult rat brain by immunohistochemistry. Absent from glia, DPP10 proteins appear mainly in the cell bodies of DPP10(+) neurons, not only at the plasma membrane but also in the cytoplasm. At least 6.4% of inhibitory interneurons in the hippocampus coexpressed Kv4.3, KChIP1, and DPP10, with the highest density in the CA1 strata alveus/oriens/pyramidale and the dentate hilus. Colocalization of Kv4.3/KChIP1/DPP10 was also detected in at least 6.9% of inhibitory interneurons scattered throughout the neocortex. Both hippocampal and neocortical Kv4.3/KChIP1/DPP10(+) inhibitory interneurons expressed parvalbumin or somatostatin, but not calbindin or calretinin. Furthermore, we found colocalization of Kv4.2/Kv4.3/KChIP3/DPP10 in neocortical layer 5 pyramidal neurons and olfactory bulb mitral cells. Together, although DPP10 is also expressed in some brain neurons lacking Kv4 (such as parvalbumin- and somatostatin-positive Golgi cells in the cerebellum), colocalization of DPP10 with Kv4 and KChIP at the plasma membrane of ISA -expressing neuron somata supports the existence of Kv4/KChIP/DPPL ternary complex in vivo. © 2014 Wiley Periodicals, Inc.

Evaluating the control of HPAIV H5N1 in Vietnam: virus transmission within infected flocks reported before and after vaccination.

PubMed

Soares Magalhães, Ricardo J; Pfeiffer, Dirk U; Otte, Joachim

2010-06-05

Currently, the highly pathogenic avian influenza virus (HPAIV) of the subtype H5N1 is believed to have reached an endemic cycle in Vietnam. We used routine surveillance data on HPAIV H5N1 poultry outbreaks in Vietnam to estimate and compare the within-flock reproductive number of infection (R0) for periods before (second epidemic wave, 2004-5; depopulation-based disease control) and during (fourth epidemic wave, beginning 2007; vaccination-based disease control) vaccination. Our results show that infected premises (IPs) in the initial (exponential) phases of outbreak periods have the highest R0 estimates. The IPs reported during the outbreak period when depopulation-based disease control was implemented had higher R0 estimates than IPs reported during the outbreak period when vaccination-based disease control was used. In the latter period, in some flocks of a defined size and species composition, within-flock transmission estimates were not significantly below the threshold for transmission (R0 < 1). Our results indicate that the current control policy based on depopulation plus vaccination has protected the majority of poultry flocks against infection. However, in some flocks the determinants associated with suboptimal protection need to be further investigated as these may explain the current pattern of infection in animal and human populations.

Performance improvement and implementation science: infection prevention competencies for current and future role development.

PubMed

Hanchett, Marilyn

2012-05-01

The Association for Professionals in Infection Control and Epidemiology, Inc, developed its first model of infection preventionist (IP) competency in 2011. The model is based on the principles of patient safety, professional and practice standards, and core competencies identified through research conducted by the Certification Board of Infection Control and Epidemiology, Inc. In addition, the model highlights 4 domains that are predicted to be key areas for future competency development. Performance improvement (PI) and implementation represent 1 of the 4 forward-focused domains. Concurrently, the inclusion of implementation science (IS) in the competency model is consistent with the research goals established by the Association for Professionals in Infection Control and Epidemiology, Inc, in its 2020 strategic plan. This article explains the importance of PI and IS and describes their relevance to the current and future IP role development. Significant challenges such as role delineation and compression are discussed. The need for the IP to acquire new competencies at integrating, as well as differentiating, PI and IS are explored in terms of emerging issues and trends. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Calcium-calmodulin-dependent kinase II modulates Kv4.2 channel expression and upregulates neuronal A-type potassium currents.

PubMed

Varga, Andrew W; Yuan, Li-Lian; Anderson, Anne E; Schrader, Laura A; Wu, Gang-Yi; Gatchel, Jennifer R; Johnston, Daniel; Sweatt, J David

2004-04-07

Calcium-calmodulin-dependent kinase II (CaMKII) has a long history of involvement in synaptic plasticity, yet little focus has been given to potassium channels as CaMKII targets despite their importance in repolarizing EPSPs and action potentials and regulating neuronal membrane excitability. We now show that Kv4.2 acts as a substrate for CaMKII in vitro and have identified CaMKII phosphorylation sites as Ser438 and Ser459. To test whether CaMKII phosphorylation of Kv4.2 affects channel biophysics, we expressed wild-type or mutant Kv4.2 and the K(+) channel interacting protein, KChIP3, with or without a constitutively active form of CaMKII in Xenopus oocytes and measured the voltage dependence of activation and inactivation in each of these conditions. CaMKII phosphorylation had no effect on channel biophysical properties. However, we found that levels of Kv4.2 protein are increased with CaMKII phosphorylation in transfected COS cells, an effect attributable to direct channel phosphorylation based on site-directed mutagenesis studies. We also obtained corroborating physiological data showing increased surface A-type channel expression as revealed by increases in peak K(+) current amplitudes with CaMKII phosphorylation. Furthermore, endogenous A-currents in hippocampal pyramidal neurons were increased in amplitude after introduction of constitutively active CaMKII, which results in a decrease in neuronal excitability in response to current injections. Thus CaMKII can directly modulate neuronal excitability by increasing cell-surface expression of A-type K(+) channels.

Cardiac P2X purinergic receptors as a new pathway for increasing Na+ entry in cardiac myocytes

PubMed Central

Shen, Jian-Bing; Yang, Ronghua; Pappano, Achilles

2014-01-01

P2X4 receptors (P2X4Rs) are ligand-gated ion channels capable of conducting cations such as Na+. Endogenous cardiac P2X4R can mediate ATP-activated current in adult murine cardiomyocytes. In the present study, we tested the hypothesis that cardiac P2X receptors can induce Na+ entry and modulate Na+ handling. We further determined whether P2X receptor-induced stimulation of the Na+/Ca2+ exchanger (NCX) has a role in modulating the cardiac contractile state. Changes in Na+-K+-ATPase current (Ip) and NCX current (INCX) after agonist stimulation were measured in ventricular myocytes of P2X4 transgenic mice using whole cell patch-clamp techniques. The agonist 2-methylthio-ATP (2-meSATP) increased peak Ip from a basal level of 0.52 ± 0.02 to 0.58 ± 0.03 pA/pF. 2-meSATP also increased the Ca2+ entry mode of INCX (0.55 ± 0.09 pA/pF under control conditions vs. 0.82 ± 0.14 pA/pF with 2-meSATP) at a membrane potential of +50 mV. 2-meSATP shifted the reversal potential of INCX from −14 ± 2.3 to −25 ± 4.1 mV, causing an estimated intracellular Na+ concentration increase of 1.28 ± 0.42 mM. These experimental results were closely mimicked by mathematical simulations based on previously established models. KB-R7943 or a structurally different agent preferentially opposing the Ca2+ entry mode of NCX, YM-244769, could inhibit the 2-meSATP-induced increase in cell shortening in transgenic myocytes. Thus, the Ca2+ entry mode of INCX participates in P2X agonist-stimulated contractions. In ventricular myocytes from wild-type mice, the P2X agonist could increase INCX, and KB-R7943 was able to inhibit the contractile effect of endogenous P2X4Rs, indicating a physiological role of these receptors in wild-type cells. The data demonstrate a novel Na+ entry pathway through ligand-gated P2X4Rs in cardiomyocytes. PMID:25239801

Cardiac P2X purinergic receptors as a new pathway for increasing Na⁺ entry in cardiac myocytes.

PubMed

Shen, Jian-Bing; Yang, Ronghua; Pappano, Achilles; Liang, Bruce T

2014-11-15

P2X4 receptors (P2X4Rs) are ligand-gated ion channels capable of conducting cations such as Na(+). Endogenous cardiac P2X4R can mediate ATP-activated current in adult murine cardiomyocytes. In the present study, we tested the hypothesis that cardiac P2X receptors can induce Na(+) entry and modulate Na(+) handling. We further determined whether P2X receptor-induced stimulation of the Na(+)/Ca(2+) exchanger (NCX) has a role in modulating the cardiac contractile state. Changes in Na(+)-K(+)-ATPase current (Ip) and NCX current (INCX) after agonist stimulation were measured in ventricular myocytes of P2X4 transgenic mice using whole cell patch-clamp techniques. The agonist 2-methylthio-ATP (2-meSATP) increased peak Ip from a basal level of 0.52 ± 0.02 to 0.58 ± 0.03 pA/pF. 2-meSATP also increased the Ca(2+) entry mode of INCX (0.55 ± 0.09 pA/pF under control conditions vs. 0.82 ± 0.14 pA/pF with 2-meSATP) at a membrane potential of +50 mV. 2-meSATP shifted the reversal potential of INCX from -14 ± 2.3 to -25 ± 4.1 mV, causing an estimated intracellular Na(+) concentration increase of 1.28 ± 0.42 mM. These experimental results were closely mimicked by mathematical simulations based on previously established models. KB-R7943 or a structurally different agent preferentially opposing the Ca(2+) entry mode of NCX, YM-244769, could inhibit the 2-meSATP-induced increase in cell shortening in transgenic myocytes. Thus, the Ca(2+) entry mode of INCX participates in P2X agonist-stimulated contractions. In ventricular myocytes from wild-type mice, the P2X agonist could increase INCX, and KB-R7943 was able to inhibit the contractile effect of endogenous P2X4Rs, indicating a physiological role of these receptors in wild-type cells. The data demonstrate a novel Na(+) entry pathway through ligand-gated P2X4Rs in cardiomyocytes. Copyright © 2014 the American Physiological Society.

49 CFR 173.427 - Transport requirements for low specific activity (LSA) Class 7 (radioactive) materials and...

Code of Federal Regulations, 2010 CFR

2010-10-01

... package (IP-1, IP-2 or IP-3; § 173.411), subject to the limitations of Table 6; (2) In a DOT Specification... use shipment 1. LSA-I: Solid IP-1 IP-1 Liquid IP-1 IP-2 2. LSA-II: Solid IP-2 IP-2 Liquid and gas IP-2 IP-3 3. LSA-III IP-2 IP-3 4. SCO-I IP-1 IP-1 5. SCO-II IP-2 IP-2 [69 FR 3676, Jan. 26, 2004; 69 FR...

49 CFR 173.427 - Transport requirements for low specific activity (LSA) Class 7 (radioactive) materials and...

Code of Federal Regulations, 2011 CFR

2011-10-01

... package (IP-1, IP-2 or IP-3; § 173.411), subject to the limitations of Table 6; (2) In a DOT Specification... use shipment 1. LSA-I: Solid IP-1 IP-1 Liquid IP-1 IP-2 2. LSA-II: Solid IP-2 IP-2 Liquid and gas IP-2 IP-3 3. LSA-III IP-2 IP-3 4. SCO-I IP-1 IP-1 5. SCO-II IP-2 IP-2 [69 FR 3676, Jan. 26, 2004; 69 FR...

Metabotropic glutamate receptors coupled to IP3 production mediate inhibition of IAHP in rat dentate granule neurons.

PubMed

Abdul-Ghani, M A; Valiante, T A; Carlen, P L; Pennefather, P S

1996-10-01

1. Whole cell recordings from dentate granule neurons in the hippocampal slice preparation reveal that (1 S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a selective agonist at metabotropic glutamate receptors (mGluRs), inhibits a calcium-activated potassium current (IAHP) responsible for the postspike after-hyperpolarization. Inclusion of 1 mM of the Ca2+ chelator ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid in the patch pipette reduced the inhibitory action of ACPD on IAHP while having no effect on a similar action of serotonin (5-HT). Thus the known action of ACPD of mobilizing intracellular Ca2+ may be involved in this inhibitor action of ACPD. 2. Inhibition of IAHP is not secondary to effects on Ca2+ currents, because 10 microM ACPD, which inhibits IAHP by 95 +/- 5% (mean +/- SE), reduced the Ca2+ current by only 8 +/- 4%. 3. Activation of mGluRs accelerates the irreversible inhibition of IAHP that develops when 88 microM GTP-gamma-S is included in the pipette filling solution, whereas inclusion of 1 mM GDP-beta-S attenuated the inhibitory action of ACPD. These results indicate that the response to mGluR activation is G protein mediated. 4. Group I mGluRs, which includes mGluR1 and mGluR5, are G-protein-coupled receptors that are known to stimulate phospholipase C (PLC)-mediated hydrolysis of phosphoinositides to produce 1,4,5-triphosphate (IP3), which in turn is known to mobilize the release of intracellular Ca2+. The weak but selective mGluR1 agonist (S)-3-hydroxyphenylglycine (100 microM) completely inhibited IAHP, and the mGluR1 antagonist (S)-4-carboxyphenylglycine (500 microM) reduced IAHP inhibition produced by 5 microM ACPD from 73 +/- 6% to 22 +/- 4%. These results indicate that the mGluR responsible for IAHP inhibition has a similar pharmacological profile to that of those coupled to IP3 production. 5. The effects of agents known to interfere with IP3 production and action also support IP3 involvement in ACPD action. Neomycin (1 mM in pipette solution), which should reduce IP3 production through inhibition of PLC, reduced the ability of 10 microM ACPD to inhibit IAHP from almost 100% to 57 +/- 8% (n = 8). Heparin, an IP3 receptor antagonist that reduces Ca2+ mobilization, attenuated the inhibitory action 10 microM ACPD from almost 100% to 39 +/- 5% (n = 5). Heparin by itself increased the amplitude and duration of IAHP, suggesting that resting levels of IP3 are sufficient to suppress of IAHP partially. 6. In addition to the pool of intracellular Ca2+ that is mobilized by IP3, there is a distinct pool that is responsible for Ca(2+)-triggered Ca2+ release and is blocked by ryanodine or dantrolene. These drugs caused a small reduction of both IAHP and the inhibitory action of ACPD. Possibly the Ca2+ signal mobilized by IP3 is partially amplified by Ca2+ released from the ryanodine-sensitive stores. 7. Activation of PLC can also lead to the production of diacylglycerol and activation of protein kinase C (PKC). However, the inhibitory action of ACPD on IAHP was not affected by staurosporine at a concentration (1 microM) that inhibits both protein kinase A (PKA) and PKC and blocks the action of 5-HT to inhibit IAHP. 8. Activation of PKA by the adenylate cyclase activator forskolin led to inhibition of IAHP. Although activation of mGluR1 agonists can also stimulate adenylate cyclase and activate PKA, inhibition of PKA and the effect of forskolin on IAHP with the Walsh peptide did not affect ACPD inhibition of IAHP. 9. All of our results support the hypothesis that mGluR-mediated inhibition of IAHP is initiated by the production of IP3 and the mobilization of intracellular Ca2+.

The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss.

PubMed

Overgaard-Steensen, Christian; Stødkilde-Jørgensen, Hans; Larsson, Anders; Tønnesen, Else; Frøkiaer, Jørgen; Ring, Troels

2016-07-01

What is the central question of this study? The brain response to acute hyponatraemia is usually studied in rodents by intraperitoneal instillation of hypotonic fluids (i.p. model). The i.p. model is described as 'dilutional' and 'syndrome of inappropriate ADH (SIADH)', but the mechanism has not been explored systematically and might affect the brain response. Therefore, in vivo brain and muscle response were studied in pigs. What is the main finding and its importance? The i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution, not dilution. A large reduction in brain sodium is observed, probably because of the specific mechanism causing the hyponatraemia. This is not accounted for in current understanding of the brain response to acute hyponatraemia. Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (i.p. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an i.p. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single i.v. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the i.p. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Preparation of pancreatic β-cells from human iPS cells with small molecules

PubMed Central

2012-01-01

Human induced pluripotent stem (iPS) cells obtained from patients are expected to be a useful source for cell transplantation therapy, because many patients (including those with type 1 diabetes and severe type 2 diabetes) are on waiting lists for transplantation for a long time due to the shortage of donors. At present, many concerns related to clinical application of human iPS cells have been raised, but rapid development of methods for the establishment, culture, and standardization of iPS cells will lead autologous cell therapy to be realistic sooner or later. However, establishment of a method for preparing some of desired cell types is still challenging. Regarding pancreatic β-cells, there have been many reports about differentiation of these cells from human embryonic stem (ES)/iPS cells, but a protocol for clinical application has still not been established. Since there is clear proof that cell transplantation therapy is effective for diabetes based on the results of clinical islet transplantation, pancreatic β-cells prepared from human iPS cells are considered likely to be effective for reducing the burden on patients. In this article, the current status of procedures for preparing pancreatic β-cells from human ES/iPS cells, including effective use of small molecules, is summarized, and some of the problems that still need to be overcome are discussed. PMID:22722666

Display Sharing: An Alternative Paradigm

NASA Technical Reports Server (NTRS)

Brown, Michael A.

2010-01-01

The current Johnson Space Center (JSC) Mission Control Center (MCC) Video Transport System (VTS) provides flight controllers and management the ability to meld raw video from various sources with telemetry to improve situational awareness. However, maintaining a separate infrastructure for video delivery and integration of video content with data adds significant complexity and cost to the system. When considering alternative architectures for a VTS, the current system's ability to share specific computer displays in their entirety to other locations, such as large projector systems, flight control rooms, and back supporting rooms throughout the facilities and centers must be incorporated into any new architecture. Internet Protocol (IP)-based systems also support video delivery and integration. IP-based systems generally have an advantage in terms of cost and maintainability. Although IP-based systems are versatile, the task of sharing a computer display from one workstation to another can be time consuming for an end-user and inconvenient to administer at a system level. The objective of this paper is to present a prototype display sharing enterprise solution. Display sharing is a system which delivers image sharing across the LAN while simultaneously managing bandwidth, supporting encryption, enabling recovery and resynchronization following a loss of signal, and, minimizing latency. Additional critical elements will include image scaling support, multi -sharing, ease of initial integration and configuration, integration with desktop window managers, collaboration tools, host and recipient controls. This goal of this paper is to summarize the various elements of an IP-based display sharing system that can be used in today's control center environment.

EPOS IP - Data, Data Products, Services and Software (DDSS Master Table)

NASA Astrophysics Data System (ADS)

Michalek, Jan; Atakan, Kuvvet

2017-04-01

The "European Plate Observing System - Implementation Phase" (EPOS IP, 2014-2019) project is about building a pan-European infrastructure for accessing solid Earth science data. This ambitious plan started in 2002 already with a Conception Phase and continued by an EPOS PP (Preparatory Phase, 2010-2014) where about 20 partners joined the project. The current EPOS IP project includes 47 partners plus 6 associate partners from 25 countries from all over Europe and several international organizations (ORFEUS, EMSC, EUREF). However, the community contributing to the EPOS integration plan is larger than the official partnership of EPOS IP project, because more countries are represented by the international organizations and because within each country there are several research institutions involved. The list of Data, Data Products, Services and Software (DDSS) provided by individual institutions, consortia or organizations which will become part of the EPOS system are currently collected in document called DDSS Master Table. There are 10 work packages (WP8-WP17) creating the Thematic Core Services (TCS) always grouped by a specific topic: Seismology, Near Fault Observatories, GNSS Data and Products, Volcano Observations, Satellite Data, Geomagnetic Observations, Anthropogenic Hazards, Geological Information and Modelling, Multi-scale laboratories and Geo-Energy Test Beds for Low Carbon Energy. Each of this group declared a list of DDSS elements which are about to be implemented. Currently there are about 455 DDSS elements in the DDSS Master Table. These DDSS elements are of different maturity and about 122 are declared by TCS groups to be ready for implementation which means that the data are well described with metadata, following the standards specific for their domain and, in the best case, with some services allowing their access already. The DDSS elements differ by its complexity as well. The DDSS Master Table serves as an overview of the DDSS elements and includes most of the important information needed for further implementation and is continuously updated as the project evolves. The presentation is showing statistics describing the current status of DDSS Master Table and complexity of the organizational structure at the TCS level.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauer, Gerry; et al.

The DAQ system of the CMS experiment at CERN collects data from more than 600 custom detector Front-End Drivers (FEDs). During 2013 and 2014 the CMS DAQ system will undergo a major upgrade to address the obsolescence of current hardware and the requirements posed by the upgrade of the LHC accelerator and various detector components. For a loss-less data collection from the FEDs a new FPGA based card implementing the TCP/IP protocol suite over 10Gbps Ethernet has been developed. To limit the TCP hardware implementation complexity the DAQ group developed a simplified and unidirectional but RFC 793 compliant version ofmore » the TCP protocol. This allows to use a PC with the standard Linux TCP/IP stack as a receiver. We present the challenges and protocol modifications made to TCP in order to simplify its FPGA implementation. We also describe the interaction between the simplified TCP and Linux TCP/IP stack including the performance measurements.« less

Inositol trisphosphate receptor mediated spatiotemporal calcium signalling.

PubMed

Miyazaki, S

1995-04-01

Spatiotemporal Ca2+ signalling in the cytoplasm is currently understood as an excitation phenomenon by analogy with electrical excitation in the plasma membrane. In many cell types, Ca2+ waves and Ca2+ oscillations are mediated by inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ channels in the endoplasmic reticulum membrane, with positive feedback between cytosolic Ca2+ and IP3-induced Ca2+ release creating a regenerative process. Remarkable advances have been made in the past year in the analysis of subcellular Ca2+ microdomains using confocal microscopy and of Ca2+ influx pathways that are functionally coupled to IP3-induced Ca2+ release. Ca2+ signals can be conveyed into the nucleus and mitochondria. Ca2+ entry from outside the cell allows repetitive Ca2+ release by providing Ca2+ to refill the endoplasmic reticulum stores, thus giving rise to frequency-encoded Ca2+ signals.

Ontogeny of cocaine-induced behaviors and cocaine pharmacokinetics in male and female neonatal, preweanling, and adult rats.

PubMed

McDougall, Sanders A; Apodaca, Matthew G; Mohd-Yusof, Alena; Mendez, Adrian D; Katz, Caitlin G; Teran, Angie; Garcia-Carachure, Israel; Quiroz, Anthony T; Crawford, Cynthia A

2018-04-18

Ontogenetic differences in the behavioral responsiveness to cocaine have often been attributed to the maturation of dopaminergic elements (e.g., dopamine transporters, D2 High receptors, receptor coupling, etc.). The purpose of this study was to determine whether ontogenetic changes in cocaine pharmacokinetics might contribute to age-dependent differences in behavioral responsiveness. Male and female neonatal (PD 5), preweanling (PD 10 and PD 20), and adult (PD 70) rats were injected (IP) with cocaine or saline and various behaviors (e.g., locomotor activity, forelimb paddle, vertical activity, head-down sniffing, etc.) were measured for 90 min. In a separate experiment, the dorsal striata of young and adult rats were removed at 10 time points (0-210 min) after IP cocaine administration. Peak cocaine values, cocaine half-life, and dopamine levels were determined using HPLC. When converted to percent of saline controls, PD 5 and PD 10 rats were generally more sensitive to cocaine than older rats, but this effect varied according to the behavior being assessed. Peak cocaine values did not differ according to age or sex, but cocaine half-life in brain was approximately 2 times longer in PD 5 and PD 10 rats than adults. Cocaine pharmacokinetics did not differ between PD 20 and PD 70 rats. Differences in the cocaine-induced behavioral responsiveness of very young rats (PD 5 and PD 10) and adults may be attributable, at least in part, to pharmacokinetic factors; whereas, age-dependent behavioral differences between the late preweanling period and adulthood cannot readily be ascribed to cocaine pharmacokinetics.

Diffusion length of positrons and positronium investigated using a positronbeam with longitudinal geometry

NASA Astrophysics Data System (ADS)

van Petegem, S.; Dauwe, C.; van Hoecke, T.; de Baerdemaeker, J.; Segers, D.

2004-09-01

Positronium emission from single crystalline Al2O3 , MgO and vitreous a-SiO2 surfaces was studied as a function of the positron implantation energy E by means of Doppler broadening spectroscopy and Compton-to-peak ratio analysis. When the Ge-detector is in-line with the positron beam, the emission of para-positronium yields a red-shifted fly-away peak with intensity IpPse . An analysis of IpPse versus E for Al2O3 and MgO where no Ps is formed in the bulk (fPs=0) results in positron diffusion lengths L+(Al2O3)=(18±1)nm and L+(MgO)=(14±1)nm , and efficiencies for the emission of Ps by picking up of a surface electron of fpu(Al2O3)=(0.28±0.2) and fpu(MgO)=(0.24±0.2) . For a-SiO2 the bulk Ps fraction is fPs(a-SiO2)=(0.72±0.01) , fpu(a-SiO2)=(0.12±0.01) and the diffusion lengths of positrons, para-positronium and ortho-positronium are L+(SiO2)=(8±2)nm , LpPs(SiO2)=(14.5±2)nm and LoPs(SiO2)=(11±2)=nm . Depending on the specimen-detector geometry the emission of Ps at low implantation energy may cause either an increase or a decrease of the width of the annihilation line shape at low implantation energies.

Anorexia induction by the trichothecene deoxynivalenol (vomitoxin) is mediated by the release of the gut satiety hormone peptide YY.

PubMed

Flannery, Brenna M; Clark, Erica S; Pestka, James J

2012-12-01

Consumption of deoxynivalenol (DON), a trichothecene mycotoxin known to commonly contaminate grain-based foods, suppresses growth of experimental animals, thus raising concerns over its potential to adversely affect young children. Although this growth impairment is believed to result from anorexia, the initiating mechanisms for appetite suppression remain unknown. Here, we tested the hypothesis that DON induces the release of satiety hormones and that this response corresponds to the toxin's anorectic action. Acute ip exposure to DON had no effect on plasma glucagon-like peptide-1, leptin, amylin, pancreatic polypeptide, gastric inhibitory peptide, or ghrelin; however, the toxin was found to robustly elevate peptide YY (PYY) and cholecystokinin (CCK). Specifically, ip exposure to DON at 1 and 5mg/kg bw induced PYY by up to 2.5-fold and CCK by up to 4.1-fold. These responses peaked within 15-120 min and lasted up to 120 min (CCK) and 240 min (PPY), corresponding with depressed rates of food intake. Direct administration of exogenous PYY or CCK similarly caused reduced food intake. Food intake experiments using the NPY2 receptor antagonist BIIE0246 and the CCK1A receptor antagonist devazepide, individually, suggested that PYY mediated DON-induced anorexia but CCK did not. Orolingual exposure to DON induced plasma PYY and CCK elevation and anorexia comparable with that observed for ip exposure. Taken together, these findings suggest that PYY might be one critical mediator of DON-induced anorexia and, ultimately, growth suppression.

Impact of sequencing depth in ChIP-seq experiments

PubMed Central

Jung, Youngsook L.; Luquette, Lovelace J.; Ho, Joshua W.K.; Ferrari, Francesco; Tolstorukov, Michael; Minoda, Aki; Issner, Robbyn; Epstein, Charles B.; Karpen, Gary H.; Kuroda, Mitzi I.; Park, Peter J.

2014-01-01

In a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) experiment, an important consideration in experimental design is the minimum number of sequenced reads required to obtain statistically significant results. We present an extensive evaluation of the impact of sequencing depth on identification of enriched regions for key histone modifications (H3K4me3, H3K36me3, H3K27me3 and H3K9me2/me3) using deep-sequenced datasets in human and fly. We propose to define sufficient sequencing depth as the number of reads at which detected enrichment regions increase <1% for an additional million reads. Although the required depth depends on the nature of the mark and the state of the cell in each experiment, we observe that sufficient depth is often reached at <20 million reads for fly. For human, there are no clear saturation points for the examined datasets, but our analysis suggests 40–50 million reads as a practical minimum for most marks. We also devise a mathematical model to estimate the sufficient depth and total genomic coverage of a mark. Lastly, we find that the five algorithms tested do not agree well for broad enrichment profiles, especially at lower depths. Our findings suggest that sufficient sequencing depth and an appropriate peak-calling algorithm are essential for ensuring robustness of conclusions derived from ChIP-seq data. PMID:24598259

A novel double gate MOSFET by symmetrical insulator packets with improved short channel effects

NASA Astrophysics Data System (ADS)

Ramezani, Zeinab; Orouji, Ali A.

2018-03-01

In this article, we study a novel double-gate SOI MOSFET structure incorporating insulator packets (IPs) at the junction between channel and source/drain (S/D) ends. The proposed MOSFET has great strength in inhibiting short channel effects and OFF-state current that are the main problems compared with conventional one due to the significant suppressed penetrations of both the lateral electric field and the carrier diffusion from the S/D into the channel. Improvement of the hot electron reliability, the ON to OFF drain current ratio, drain-induced barrier lowering, gate-induced drain leakage and threshold voltage over conventional double-gate SOI MOSFETs, i.e. without IPs, is displayed with the simulation results. This study is believed to improve the CMOS device reliability and is suitable for the low-power very-large-scale integration circuits.

Startle Potentiation to Uncertain Threat as a Psychophysiological Indicator of Fear-based Psychopathology: An Examination across Multiple Internalizing Disorders

PubMed Central

Gorka, Stephanie M.; Lieberman, Lynne; Shankman, Stewart A.; Phan, K. Luan

2016-01-01

Heightened reactivity to uncertain threat (U-threat) is an important individual difference factor that may characterize fear-based internalizing psychopathologies (IPs) and distinguish them from distress/misery IPs. To date, however, the majority of existing research examining reactivity to U-threat has been within individuals with panic disorder and major depressive disorder (MDD) and no prior study has directly tested this hypothesis across multiple IPs. The current study therefore explored whether heightened reactivity to U-threat is a psychophysiological indicator of fear-based psychopathology across five groups: current 1) social anxiety disorder (SAD), 2) specific phobia (SP), 3) generalized anxiety disorder (GAD), 4) MDD, and 5) individuals with no history of psychopathology (controls). All 160 adults completed a well-validated threat-of-shock task designed to probe responses to predictable (P-) and U-threat. Startle eyeblink potentiation was recorded as an index of aversive arousal. Results indicated that individuals with SAD and SP evidenced greater startle potentiation to U-threat, but not P-threat, relative to individuals with GAD, MDD and controls (who did not differ). The current findings, along with the prior panic disorder and MDD literature, suggest that heightened reactivity to U-threat is a psychophysiological indicator of fear-based disorders and could represent a neurobiological organizing principle for internalizing psychopathology. The findings also suggest that individuals with fear disorders generally display a hypersensitivity to uncertain aversive events, which could contribute to their psychopathology. PMID:27868423

Correlated peak relative light intensity and peak current in triggered lightning subsequent return strokes

NASA Technical Reports Server (NTRS)

Idone, V. P.; Orville, R. E.

1985-01-01

The correlation between peak relative light intensity L(R) and stroke peak current I(R) is examined for 39 subsequent return strokes in two triggered lightning flashes. One flash contained 19 strokes and the other 20 strokes for which direct measurements were available of the return stroke peak current at ground. Peak currents ranged from 1.6 to 21 kA. The measurements of peak relative light intensity were obtained from photographic streak recordings using calibrated film and microsecond resolution. Correlations, significant at better than the 0.1 percent level, were found for several functional relationships. Although a relation between L(R) and I(R) is evident in these data, none of the analytical relations considered is clearly favored. The correlation between L(R) and the maximum rate of current rise is also examined, but less correlation than between L(R) and I(R) is found. In addition, the peak relative intensity near ground is evaluated for 22 dart leaders, and a mean ratio of peak dart leader to peak return stroke relative light intensity was found to be 0.1 with a range of 0.02-0.23. Using two different methods, the peak current near ground in these dart leaders is estimated to range from 0.1 to 6 kA.

Clinical Diagnostic Utility of IP-10 and LAM Antigen Levels for the Diagnosis of Tuberculous Pleural Effusions in a High Burden Setting

PubMed Central

Dheda, Keertan; Van-Zyl Smit, Richard N.; Sechi, Leonardo A.; Badri, Motasim; Meldau, Richard; Symons, Gregory; Khalfey, Hoosein; Carr, Igshaan; Maredza, Alice; Dawson, Rodney; Wainright, Helen; Whitelaw, Andrew; Bateman, Eric D.; Zumla, Alimuddin

2009-01-01

Background Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-γ-inducible-10kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid. Methods We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis. Principal Findings Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed ∼20% of TB cases and mis-diagnosed ∼20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful. Conclusion Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings. PMID:19277111

On recovering distributed IP information from inductive source time domain electromagnetic data

NASA Astrophysics Data System (ADS)

Kang, Seogi; Oldenburg, Douglas W.

2016-10-01

We develop a procedure to invert time domain induced polarization (IP) data for inductive sources. Our approach is based upon the inversion methodology in conventional electrical IP (EIP), which uses a sensitivity function that is independent of time. However, significant modifications are required for inductive source IP (ISIP) because electric fields in the ground do not achieve a steady state. The time-history for these fields needs to be evaluated and then used to define approximate IP currents. The resultant data, either a magnetic field or its derivative, are evaluated through the Biot-Savart law. This forms the desired linear relationship between data and pseudo-chargeability. Our inversion procedure has three steps: (1) Obtain a 3-D background conductivity model. We advocate, where possible, that this be obtained by inverting early-time data that do not suffer significantly from IP effects. (2) Decouple IP responses embedded in the observations by forward modelling the TEM data due to a background conductivity and subtracting these from the observations. (3) Use the linearized sensitivity function to invert data at each time channel and recover pseudo-chargeability. Post-interpretation of the recovered pseudo-chargeabilities at multiple times allows recovery of intrinsic Cole-Cole parameters such as time constant and chargeability. The procedure is applicable to all inductive source survey geometries but we focus upon airborne time domain EM (ATEM) data with a coincident-loop configuration because of the distinctive negative IP signal that is observed over a chargeable body. Several assumptions are adopted to generate our linearized modelling but we systematically test the capability and accuracy of the linearization for ISIP responses arising from different conductivity structures. On test examples we show: (1) our decoupling procedure enhances the ability to extract information about existence and location of chargeable targets directly from the data maps; (2) the horizontal location of a target body can be well recovered through inversion; (3) the overall geometry of a target body might be recovered but for ATEM data a depth weighting is required in the inversion; (4) we can recover estimates of intrinsic τ and η that may be useful for distinguishing between two chargeable targets.

Transcriptomic and epigenomic characterization of the developing bat wing

PubMed Central

Eckalbar, Walter L.; Schlebusch, Stephen A.; Mason, Mandy K.; Gill, Zoe; Parker, Ash V.; Booker, Betty M.; Nishizaki, Sierra; Muswamba-Nday, Christiane; Terhune, Elizabeth; Nevonen, Kimberly; Makki, Nadja; Friedrich, Tara; VanderMeer, Julia E.; Pollard, Katherine S.; Carbone, Lucia; Wall, Jeff D.; Illing, Nicola; Ahituv, Nadav

2016-01-01

Bats are the only mammals capable of powered flight, but little is known about the genetic determinants that shape their wings. Here, we generated a genome for Miniopterus natalensis and performed RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on its developing forelimb and hindlimb autopods at sequential embryonic stages to decipher the molecular events that underlie bat wing development. Over 7,000 genes and several lncRNAs, including Tbx5-as1 and Hottip, were differentially expressed between forelimb, hindlimb and different stages. ChIP-seq identified thousands of regions that are differentially modified in forelimb versus hindlimb. Comparative genomics found 2,796 bat-accelerated regions within H3K27ac peaks, several of which cluster near limb-associated genes. Pathway analyses revealed multiple ribosomal proteins and known limb patterning signaling pathways as differentially regulated, and implicated increased forelimb mesenchymal condensations with differential growth. Combined, our work outlines multiple genetic components that contribute to bat wing formation, providing a genomic blueprint for this morphological innovation. PMID:27019111

Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium.

PubMed

Knapp, J; Bokník, P; Linck, B; Läer, S; Müller, F U; Neumann, J; Vahlensieck, U; Schlüter, H; Zidek, W; Schmitz, W

1999-09-01

In human ventricular trabeculae carneae 100 microM AP4A (diadenosine tetraphosphate) increased force of contraction to 162.8+/-15.7% of predrug value (n=9). This positive inotropic effect was accompanied by a prolongation of time parameters: time to peak tension and time of relaxation were prolonged by 7.8+/-1.3% and 14.9+/-3.8%, respectively (P<0.05). In the same trabeculae, AP4A increased IP3 (inositol-1,4,5-trisphosphate) content from 9.0+/-1.3 pmol/mg to 22.9+/-5.4 pmol/mg protein (n=5-9). In conclusion, the positive inotropic effect of AP4A in the human myocardium is likely due to an increase of IP3 mediated probably via Gq-coupled P2Y-purinoceptors. Because of the prominent role of Gq in the development of cardiac disease, these findings may lay the ground to further investigate the possible role of AP4A and/or related ligands (e.g. AP2A and AP3A) in heart failure.

The Iron Project

NASA Technical Reports Server (NTRS)

Pradhan, Anil K.

2000-01-01

Recent advances in theoretical atomic physics have enabled large-scale calculation of atomic parameters for a variety of atomic processes with high degree of precision. The development and application of these methods is the aim of the Iron Project. At present the primary focus is on collisional processes for all ions of iron, Fe I - FeXXVI, and other iron-peak elements; new work on radiative processes has also been initiated. Varied applications of the Iron Project work to X-ray astronomy are discussed, and more general applications to other spectral ranges are pointed out. The IP work forms the basis for more specialized projects such as the RmaX Project, and the work on photoionization/recombination, and aims to provide a comprehensive and self-consistent set of accurate collisional and radiative cross sections, and transition probabilities, within the framework of relativistic close coupling formulation using the Breit-Pauli R-Matrix method. An illustrative example is presented of how the IP data may be utilized in the formation of X-ray spectra of the K alpha complex at 6.7 keV from He-like Fe XXV.

Long pulse high performance plasma scenario development for the National Spherical Torus Experiment

NASA Astrophysics Data System (ADS)

Kessel, C. E.; Bell, R. E.; Bell, M. G.; Gates, D. A.; Kaye, S. M.; LeBlanc, B. P.; Menard, J. E.; Phillips, C. K.; Synakowski, E. J.; Taylor, G.; Wilson, R.; Harvey, R. W.; Mau, T. K.; Ryan, P. M.; Sabbagh, S. A.

2006-05-01

The National Spherical Torus Experiment [Ono et al., Nucl. Fusion, 44, 452 (2004)] is targeting long pulse high performance, noninductive sustained operations at low aspect ratio, and the demonstration of nonsolenoidal startup and current rampup. The modeling of these plasmas provides a framework for experimental planning and identifies the tools to access these regimes. Simulations based on neutral beam injection (NBI)-heated plasmas are made to understand the impact of various modifications and identify the requirements for (1) high elongation and triangularity, (2) density control to optimize the current drive, (3) plasma rotation and/or feedback stabilization to operate above the no-wall β limit, and (4) electron Bernstein waves (EBW) for off-axis heating/current drive (H/CD). Integrated scenarios are constructed to provide the transport evolution and H/CD source modeling, supported by rf and stability analyses. Important factors include the energy confinement, Zeff, early heating/H mode, broadening of the NBI-driven current profile, and maintaining q(0) and qmin>1.0. Simulations show that noninductive sustained plasmas can be reached at IP=800 kA, BT=0.5 T, κ≈2.5, βN⩽5, β⩽15%, fNI=92%, and q(0)>1.0 with NBI H/CD, density control, and similar global energy confinement to experiments. The noninductive sustained high β plasmas can be reached at IP=1.0 MA, BT=0.35 T, κ≈2.5, βN⩽9, β⩽43%, fNI=100%, and q(0)>1.5 with NBI H/CD and 3.0 MW of EBW H/CD, density control, and 25% higher global energy confinement than experiments. A scenario for nonsolenoidal plasma current rampup is developed using high harmonic fast wave H/CD in the early low IP and low Te phase, followed by NBI H/CD to continue the current ramp, reaching a maximum of 480 kA after 3.4 s.

Role of N-terminal domain and accessory subunits in controlling deactivation-inactivation coupling of Kv4.2 channels.

PubMed

Barghaan, Jan; Tozakidou, Magdalini; Ehmke, Heimo; Bähring, Robert

2008-02-15

We examined the relationship between deactivation and inactivation in Kv4.2 channels. In particular, we were interested in the role of a Kv4.2 N-terminal domain and accessory subunits in controlling macroscopic gating kinetics and asked if the effects of N-terminal deletion and accessory subunit coexpression conform to a kinetic coupling of deactivation and inactivation. We expressed Kv4.2 wild-type channels and N-terminal deletion mutants in the absence and presence of Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-like proteins (DPPs) in human embryonic kidney 293 cells. Kv4.2-mediated A-type currents at positive and deactivation tail currents at negative membrane potentials were recorded under whole-cell voltage-clamp and analyzed by multi-exponential fitting. The observed changes in Kv4.2 macroscopic inactivation kinetics caused by N-terminal deletion, accessory subunit coexpression, or a combination of the two maneuvers were compared with respective changes in deactivation kinetics. Extensive correlation analyses indicated that modulatory effects on deactivation closely parallel respective effects on inactivation, including both onset and recovery kinetics. Searching for the structural determinants, which control deactivation and inactivation, we found that in a Kv4.2 Delta 2-10 N-terminal deletion mutant both the initial rapid phase of macroscopic inactivation and tail current deactivation were slowed. On the other hand, the intermediate and slow phase of A-type current decay, recovery from inactivation, and tail current decay kinetics were accelerated in Kv4.2 Delta 2-10 by KChIP2 and DPPX. Thus, a Kv4.2 N-terminal domain, which may control both inactivation and deactivation, is not necessary for active modulation of current kinetics by accessory subunits. Our results further suggest distinct mechanisms for Kv4.2 gating modulation by KChIPs and DPPs.

Calibration and application of the IP25 biomarker for Arctic sea ice reconstructions

NASA Astrophysics Data System (ADS)

Cabedo Sanz, P.; Navarro Rodriguez, A.; Belt, S. T.; Brown, T. A.; Knies, J.; Husum, K.; Giraudeau, J.; Andrews, J.

2012-04-01

The presence of the sea ice diatom biomarker IP25 in Arctic marine sediments has been used in previous studies as a proxy for past spring sea ice occurrence and as an indicator of wider palaeoenvironmental conditions for different regions of the Arctic over various timescales [e.g. 1, 3]. In addition, measurement of IP25 has also been applied as a sea ice origin tracer for studying the transfer of organic carbon through Arctic food-webs [2]. The current study focuses on three main areas: (1) In order to improve on the quantitative analytical aspects of IP25 based research, we present here the results of a large scale extraction, purification and identification procedure for IP25 from marine sediments. This has confirmed the structure of IP25 in sediments and enabled more robust quantitative measurements by gas chromatography - mass spectrometry (GC-MS) to be established. (2) Quantitative measurements of IP25 from a sediment core from Andfjord (continental shelf, Tromsø, Norway) have been determined for the period 6.3 to 14.3 ka BP. The results of this study add significant further information to that reported previously from other biomarker studies for this core (e.g. brassicasterol) [4]. (3) Analytical detection issues (GC-MS) regarding the occurrence of IP25 in other sub-Arctic regions (e.g. East Greenland - North Iceland area) will be presented and discussed with relation to other proxy data (e.g. IRD). Belt, S. T., Vare, L. L., Massé, G., Manners, H. R., Price, J. C., MacLachlan, S. E., Andrews, J. T. & Schmidt, S. (2010) 'Striking similarities in temporal changes to spring sea ice occurrence across the central Canadian Arctic Archipelago over the last 7000 years', Quaternary Science Reviews, 29 (25-26), pp. 3489-3504. Brown, T. A. & Belt, S. T. (2012) 'Identification of the sea ice diatom biomarker IP25 in Arctic benthic macrofauna: direct evidence for a sea ice diatom diet in Arctic heterotrophs', Polar Biology, 35, pp. 131-137. Müller, J., Massé, G., Stein, R. & Belt, S. T. (2009) 'Variability of sea-ice conditions in the Fram Strait over the past 30,000 years', Nature Geoscience, 2 (11), pp. 772-776. .Knies, J. (2005) 'Climate-induced changes in sedimentary regimes for organic matter supply on the continental shelf off northern Norway', Geochimica et Cosmochimica Acta, 69 (19), pp. 4631-4647.

Postoperative Outcomes of Extremely Low Birth-Weight Infants With Necrotizing Enterocolitis or Isolated Intestinal Perforation

PubMed Central

Blakely, Martin L.; Lally, Kevin P.; McDonald, Scott; Brown, Rebeccah L.; Barnhart, Douglas C.; Ricketts, Richard R.; Thompson, W Raleigh; Scherer, L R.; Klein, Michael D.; Letton, Robert W.; Chwals, Walter J.; Touloukian, Robert J.; Kurkchubasche, Arlett G.; Skinner, Michael A.; Moss, R Lawrence; Hilfiker, Mary L.

2005-01-01

Objective: Purposes of this study were: 1) to compare mortality and postoperative morbidities (intra-abdominal abscess, wound dehiscence, and intestinal stricture) in extremely low birth weight (ELBW) infants who underwent initial laparotomy or drainage for necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP); 2) to determine the ability to distinguish NEC from IP preoperatively and the importance of this distinction on outcome measures; and 3) to evaluate the association between extent of intestinal disease determined at operation and outcome measures. Background: ELBW infants who undergo operation for NEC or IP have a postoperative, in-hospital mortality rate of approximately 50%. Whether to perform laparotomy or drainage initially is controversial. Also unknown is the importance of distinguishing NEC from IP and the current ability to make this distinction based on objective data available prior to operation. Methods: A prospective, multicenter cohort study of 156 ELBW infants at 16 neonatal intensive care units (NICU) within the NICHD Neonatal Research Network. Results: Among the 156 enrolled infants, 80 underwent initial peritoneal drainage and 76 initial laparotomy. Mortality rate was 49% (76 of 156). Ninety-six patients had a preoperative diagnosis of NEC and 60 had presumed IP. There was a high level of agreement between the presumed preoperative diagnosis and intraoperative diagnosis in patients undergoing initial laparotomy (kappa = 0.85). The relative risk for death with a preoperative diagnosis of NEC (versus IP) was 1.4 (95% confidence interval, 0.99–2.1, P = 0.052). The overall incidence of postoperative intestinal stricture was 10.3%, wound dehiscence 4.4%, and intra-abdominal abscess 5.8%, and did not significantly differ between groups undergoing initial laparotomy versus initial drainage. Conclusions: Survival to hospital discharge after operation for NEC or IP in ELBW neonates remains poor (51%). Patients with a preoperative diagnosis of NEC have a relative risk for death of 1.4 compared with those with a preoperative diagnosis of IP. A distinction can be made preoperatively between NEC and IP based on abdominal radiographic findings and the patient's age at operation. Future randomized trials that compare laparotomy versus drainage would likely benefit from stratification of treatment assignment based on preoperative diagnosis. PMID:15912048

STS-35 MS Hoffman operates ASTRO-1 MPC on OV-102's aft flight deck

NASA Image and Video Library

1990-12-10

STS035-12-015 (2-11 Dec 1990) --- Astronaut Jeffrey A. Hoffman, STS 35 mission specialist, uses a manual pointing controller (MPC) for the Astro-1 mission's Instrument Pointing System (IPS). By using the MPC, Hoffman and other crewmembers on Columbia's aft flight deck, were able to command the IPS, located in the cargo bay, to record astronomical data. Hoffman is serving the "Blue" shift which complemented the currently sleeping "Red" shift of crewmembers as the mission collected scientific data on a 24-hour basis. The scene was photographed with a 35mm camera.

Epigenetic modulation by TFII-I during embryonic stem cell differentiation.

PubMed

Bayarsaihan, Dashzeveg; Makeyev, Aleksandr V; Enkhmandakh, Badam

2012-10-01

TFII-I transcription factors play an essential role during early vertebrate embryogenesis. Genome-wide mapping studies by ChIP-seq and ChIP-chip revealed that TFII-I primes multiple genomic loci in mouse embryonic stem cells and embryonic tissues. Moreover, many TFII-I-bound regions co-localize with H3K4me3/K27me3 bivalent chromatin within the promoters of lineage-specific genes. This minireview provides a summary of current knowledge regarding the function of TFII-I in epigenetic control of stem cell differentiation. Copyright © 2012 Wiley Periodicals, Inc.

N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis: results from the Norfolk Arthritis Registry (NOAR)

PubMed Central

Mirjafari, Hoda; Welsh, Paul; Verstappen, Suzanne M M; Wilson, Paddy; Marshall, Tarnya; Edlin, Helena; Bunn, Diane; Chipping, Jacqueline; Lunt, Mark; Symmons, Deborah P M; Sattar, Naveed; Bruce, Ian N

2014-01-01

Background We measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a marker of cardiac dysfunction, in an inception cohort with early inflammatory polyarthritis (IP) and assessed its association with disease phenotype, cardiovascular disease (CVD), all-cause and CVD related mortality. Methods Subjects with early IP were recruited to the Norfolk Arthritis Register from January 2000 to December 2008 and followed up to death or until March 2010 including any data from the national death register. The associations of baseline NT-pro-BNP with IP related factors and CVD were assessed by linear regression. Cox proportional hazards models examined the independent association of baseline NT-pro-BNP with all-cause and CVD mortality. Results We studied 960 early IP subjects; 163 (17%) had prior CVD. 373 (39%) patients had a baseline NT-pro-BNP levels ≥100 pg/ml. NT-pro-BNP was associated with age, female gender, HAQ score, CRP, current smoking, history of hypertension, prior CVD and the presence of carotid plaque. 92 (10%) IP subjects died including 31 (3%) from CVD. In an age and gender adjusted analysis, having a raised NT-pro-BNP level (≥100 pg/ml) was associated with both all-cause and CVD mortality (adjusted HR (95% CI) 2.36 (1.42 to 3.94) and 3.40 (1.28 to 9.03), respectively). These findings were robust to adjustment for conventional CVD risk factors and prevalent CVD. Conclusions In early IP patients, elevated NT-pro-BNP is related to HAQ and CRP and predicts all-cause and CVD mortality independently of conventional CVD risk factors. Further study is required to identify whether NT-pro-BNP may be clinically useful in targeting intensive interventions to IP patients at greatest risk of CVD. PMID:23511225

Evaluation of insecticides for protecting Southwestern ponderosa pines from attack by engraver beetles (Coleoptera: Curculionidae: Scolytinae).

PubMed

DeGomez, Tom E; Hayes, Christopher J; Anhold, John A; McMillin, Joel D; Clancy, Karen M; Bosu, Paul P

2006-04-01

Insecticides that might protect pine trees from attack by engraver beetles (Ips spp.) have not been rigorously tested in the southwestern United States. We conducted two field experiments to evaluate the efficacy of several currently and potentially labeled preventative insecticides for protecting high-value ponderosa pine, Pinus ponderosa Dougl ex. Laws., from attack by engraver beetles. Preventative sprays (0.19% permethrin [Permethrin Plus C]; 0.03, 0.06, and 0.12% bifenthrin [Onyx]; and 1.0 and 2.0% carbaryl [Sevin SL] formulations) and systemic implants (0.875 g per capsule acephate [Acecap] and 0.650 g per capsule dinotefuran) were assessed on bolts (sections of logs) as a surrogate for live trees for a period of 13 mo posttreatment. The pine engraver, Ips pini (Say), was the most common bark beetle found attacking control and treated bolts, but sixspined ips, Ips calligraphus (Germar), and Ips lecontei Swain also were present. After approximately 13 mo posttreatment in one experiment, the spray treatments with 2.0% carbaryl, 0.19% permethrin, and 0.06 or 0.12% bifenthrin prevented Ips attack on the bolts at a protection level of > or = 70%. The acephate and dinotefuran systemic insecticides, and the 0.03% bifenthrin spray, provided inadequate (< or = 36%) protection in this experiment. For the other experiment, sprayed applications of 1.0% carbaryl, 0.19% permethrin, and 0.06% bifenthrin prevented beetle attack at protection levels of > or = 90, > or = 80, and > or = 70%, respectively, when bolts were exposed to Ips beetle attack for approximately 9-15 wk posttreatment. The sprays with 0.19% permethrin and 0.06% bifenthrin also provided > or = 90% protection when bolts were exposed for approximately 15-54 wk posttreatment. We concluded that under the conditions tested, 1.0 and 2.0% carbaryl, 0.19% permethrin, and 0.06 and 0.12% binfenthrin were acceptable preventative treatments for protecting ponderosa pine from successful engraver beetle attack for one entire flight season in the U.S. Southwest.

The Worldwide Interplanetary Scintillation (IPS) Stations (WIPSS) Network in support of Space-Weather Science and Forecasting

NASA Astrophysics Data System (ADS)

Bisi, M. M.; Gonzalez-Esparza, A.; Jackson, B. V.; Aguilar-Rodriguez, E.; Tokumaru, M.; Chashei, I. V.; Tyul'bashev, S. A.; Manoharan, P. K.; Fallows, R. A.; Chang, O.; Mejia-Ambriz, J. C.; Yu, H. S.; Fujiki, K.; Shishov, V.

2016-12-01

The phenomenon of space weather - analogous to terrestrial weather which describes the changing low-altitude atmospheric conditions on Earth - is essentially a description of the changes in the plasma environment at and near the Earth. Some key parameters for space-weather purposes driving space weather at the Earth include velocity, density, magnetic field, high-energy particles, and radiation coming into and within the near-Earth space environment. Interplanetary scintillation (IPS) can be used to provide a global measure of velocity and density as well as indications of changes in the plasma and magnetic-field rotations along each observational line of sight. If the observations are formally inverted into a three-dimensional (3-D) tomographic reconstruction (such as using the University of California, San Diego - UCSD - kinematic model and reconstruction technique), then source-surface magnetic fields can also be propagated out to the Earth (and beyond) as well as in-situ data also being incorporated into the reconstruction. Currently, this has been done using IPS data only from the Institute for Space-Earth Environmental (ISEE) and has been scientifically since the 1990s, and in a forecast mode since around 2000. There is now a defined IPS Common Data Format (IPSCDFv1.0) which is being implemented by the majority of the IPS community (this also feeds into the tomography). The Worldwide IPS Stations (WIPSS) Network aims to bring together, using IPSCDFv1.0, the worldwide real-time capable IPS observatories with well-developed and tested analyses techniques being unified across all single-site systems (such as MEXART, Pushchino, and Ooty) and cross-calibrated to the multi-site ISEE system (as well as learning from the scientific-based systems such as EISCAT, LOFAR, and the MWA), into the UCSD 3-D tomography to improve the accuracy, spatial and temporal data coverage, and both the spatial and temporal resolution for improved space-weather science and forecast capabilities.

The Worldwide Interplanetary Scintillation (IPS) Stations (WIPSS) Network in support of Space-Weather Science and Forecasting

NASA Astrophysics Data System (ADS)

Bisi, Mario Mark; Americo Gonzalez-Esparza, J.; Jackson, Bernard; Aguilar-Rodriguez, Ernesto; Tokumaru, Munetoshi; Chashei, Igor; Tyul'bashev, Sergey; Manoharan, Periasamy; Fallows, Richard; Chang, Oyuki; Yu, Hsiu-Shan; Fujiki, Ken'ichi; Shishov, Vladimir; Barnes, David

2017-04-01

The phenomenon of space weather - analogous to terrestrial weather which describes the changing low-altitude atmospheric conditions on Earth - is essentially a description of the changes in the plasma environment at and near the Earth. Some key parameters for space-weather purposes driving space weather at the Earth include velocity, density, magnetic field, high-energy particles, and radiation coming into and within the near-Earth space environment. Interplanetary scintillation (IPS) can be used to provide a global measure of velocity and density as well as indications of changes in the plasma and magnetic-field rotations along each observational line of sight. If the observations are formally inverted into a three-dimensional (3-D) tomographic reconstruction (such as using the University of California, San Diego - UCSD - kinematic model and reconstruction technique), then source-surface magnetic fields can also be propagated out to the Earth (and beyond) as well as in-situ data also being incorporated into the reconstruction. Currently, this has been done using IPS data only from the Institute for Space-Earth Environmental (ISEE) and has been scientifically since the 1990s, and in a forecast mode since around 2000. There is now a defined (and updated) IPS Common Data Format (IPSCDFv1.1) which is being implemented by the majority of the IPS community (this also feeds into the UCSD tomography). The Worldwide IPS Stations (WIPSS) Network aims to bring together, using IPSCDFv1.1, the worldwide real-time capable IPS observatories with well-developed and tested analyses techniques being unified across all single-site systems (such as MEXART, Pushchino, and Ooty) and cross-calibrated to the multi-site ISEE system (as well as learning from the scientific-based systems such as EISCAT, LOFAR, and the MWA), into the UCSD 3-D tomography to improve the accuracy, spatial and temporal data coverage, and both the spatial and temporal resolution for improved space-weather science and forecast capabilities.

The MEXART ips observations in route to the next solar maximum

NASA Astrophysics Data System (ADS)

Carrillo-Vargas, Armando; Gonzalez-Esparza, Americo; Andrade, Ernesto; Perez-Enriquez, Roman; Aguilar-Rodriguez, Ernesto; Casillas-Perez, Gilberto; Jeyakumar, Solai; Kurtz, Stanley; Sierra, Pablo; Vazquez, Samuel

We report the status of the Mexican Array Radio Telescope (MEXART) in preparation for the next solar maximum. During this epoch, the MEXART will be one of the four dedicated radio telescopes (with the ORT in India; STEL in Japan; and MWA in Australia) to track large-scale structures in the solar wind using the interplanetary scintillation (IPS) technique. This network of IPS observatories would produce, for the first time four g maps of the sky showing the size and shape of disturbances between the Sun and the Earth. We describe the operation and current observations of the first IPS radio sources at 140 MHz detected by the MEXART. These observations use a plane dipole array of 1024 elements (16 lines with 64 dipoles each one), feeding a Butler matrix of 16x16 ports. This system generates a 16 lobes at fixed declinations covering 120 degrees (from 40 degrees South to 80 degrees North). The beam fan uses the Earth's rotation to cover the whole sky. The observations that will be made with the network of observatories of interplanetary flashing will complement the observations of other observatories, instruments in situ, space probes, satellite, among others.

Melanopsin-based brightness discrimination in mice and humans.

PubMed

Brown, Timothy M; Tsujimura, Sei-Ichi; Allen, Annette E; Wynne, Jonathan; Bedford, Robert; Vickery, Graham; Vugler, Anthony; Lucas, Robert J

2012-06-19

Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection, no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance-a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

a New Ubiquitous-Based Indoor Positioning System with Minimum Extra Hardware Using Smart Phones

NASA Astrophysics Data System (ADS)

Hassany Pazoky, S.; Chehreghan, A.; Sadeghi Niaraki, A.; Abbaspour, R. Ali

2014-10-01

Knowing the position has been an ambition in many areas such as science, military, business, etc. GPS was the realization of this wish in 1970s. Technological advances such as ubiquitous computing, as a conquering perspective, requires any service to work for any user, any place, anytime, and via any network. As GPS cannot provide services in indoor environments, many scientists began to develop indoor positioning systems (IPS). Smart phones penetrating our everyday lives were a great platform to host IPS applications. Sensors in smart phones were another big motive to develop IPS applications. Many researchers have been working on the topic developing various applications. However, the applications introduced lack simplicity. In other words, they need to install a step counter or smart phone on the ankle, which makes it awkward and inapplicable in many situations. In the current study, a new IPS methodology is introduced using only the usual embedded sensors in the smart phones. The robustness of this methodology cannot compete with those of the aforementioned approaches. The price paid for simplicity was decreasing robustness and complicating the methods and formulations. However, methods or tricks to harness the errors to an acceptable range are introduced as the future works.

Skull Base Inverted Papilloma: A Comprehensive Review

PubMed Central

Wassef, Shafik N.; Batra, Pete S.; Barnett, Samuel

2012-01-01

Skull base inverted papilloma (IP) is an unusual entity for many neurosurgeons. IP is renowned for its high rate of recurrence, its ability to cause local destruction, and its association with malignancy. This paper is a comprehensive review of the reports, studies, and reviews published in the current biomedical literature from 1947 to September 2010 and synthesize this information to focus on its potential invasion to the base of the skull and possible intradural extension. The objective is to familiarize the clinician with the different aspects of this unusual disease. The role of modern diagnostic tools in medical imaging in order to assess clearly the limits of the tumors and to enhance the efficiency and the safety in the choice of a surgical approach is pointed out. The treatment guidelines for IP have undergone a complex evolution that continues today. Radical excision of the tumour is technically difficult and often incomplete. Successful management of IP requires resection of the affected mucosa which could be achieved with open surgery, endoscopic, or combined approach. Radio and chemotherapy were used for certain indications. More optimally research would be a multicenter randomized trials with large size cohorts. PMID:23346418

Altered plasma levels of chemokines in autism and their association with social behaviors.

PubMed

Shen, Yidong; Ou, JInajun; Liu, Mengmeng; Shi, Lijuan; Li, Yamin; Xiao, Lu; Dong, Huixi; Zhang, Fengyu; Xia, Kun; Zhao, Jingping

2016-10-30

Autism Spectrum Disorder (ASD) is a group of neurodevelopment disorders with an unclear etiology. Chemokines have been implicated in the etiology and pathogenesis of ASD. The current study investigated the plasma levels of seven chemokines (RANTES, Eotaxin, MIP-1 α, MIP-1 β, MCP-1, IP-10, and MIG) in 42 young autistic patients and 35 age-matched typically developing (TD) children. The study also tested the association between these chemokine levels and social behaviors, as measured by the Social Responsiveness Scale (SRS). Compared to the TD children, RANTES, MIP-1α, and MIP-1β were higher, while IP-10 and MIG were lower in the autistic patients, after correcting for multiple comparisons. Among these seven chemokines, MIP-1α, MIP-1β and IP-10 levels were found to be associated with social behaviors in all the participants. Moreover, MIP-1α and IP-10 were found to be independent predictors of social behaviors. The results of our study support the hypothesis that altered chemokine levels are involved in the pathophysiology of ASD and they indicate that chemokines plasma levels could be potential biomarkers for ASD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Left Posterior Parietal Cortex Participates in Both Task Preparation and Episodic Retrieval

PubMed Central

Phillips, Jeffrey S.; Velanova, Katerina; Wolk, David A.; Wheeler, Mark E.

2012-01-01

Optimal memory retrieval depends not only on the fidelity of stored information, but also on the attentional state of the subject. Factors such as mental preparedness to engage in stimulus processing can facilitate or hinder memory retrieval. The current study used functional magnetic resonance imaging (fMRI) to distinguish preparatory brain activity before episodic and semantic retrieval tasks from activity associated with retrieval itself. A catch-trial imaging paradigm permitted separation of neural responses to preparatory task cues and memory probes. Episodic and semantic task preparation engaged a common set of brain regions, including the bilateral intraparietal sulcus (IPS), left fusiform gyrus (FG), and the pre-supplementary motor area (pre-SMA). In the subsequent retrieval phase, the left IPS was among a set of frontoparietal regions that responded differently to old and new stimuli. In contrast, the right IPS responded to preparatory cues with little modulation during memory retrieval. The findings support a strong left-lateralization of retrieval success effects in left parietal cortex, and further indicate that left IPS performs operations that are common to both task preparation and memory retrieval. Such operations may be related to attentional control, monitoring of stimulus relevance, or retrieval. PMID:19285142

Light as a central modulator of circadian rhythms, sleep and affect

PubMed Central

LeGates, T.A.; Fernandez, D.C.; Hattar, S

2014-01-01

Light has profoundly influenced the evolution of life on earth. As widely appreciated, light allows us to generate images of our environment. However, light, through the atypical intrinsically photosensitive retinal ganglion cells (ipRGCs; Box 1), also influences behaviors that are essential for our health and quality of life, yet are independent of image formation. These include the synchronization of the circadian clock to the solar day, tracking of seasonal changes, and regulation of sleep. Irregular light environments lead to problems in circadian rhythms and sleep, which eventually cause mood and learning deficits. Recently, it was found that irregular light can also directly impact mood and learning without producing major disruptions in circadian rhythms and sleep. Here, we will discuss the indirect and direct influence of light on mood and learning and provide a model for how light, the circadian clock, and sleep interact to influence mood and cognitive functions. Box 1Intrinsically photosensitive retinal ganglion cells (ipRGCs)Retinal photoreceptors transduce light energy into electrical signals that initiate vision. The classical photoreceptors, rods and cones, possess modified cilia that consist of stacks of membranes in which photopigments (rhodopsin and cone opsins) are concentrated. Rods are exquisitely sensitive and are able to detect even a few photons. Rods are therefore used for night vision. Cones are less sensitive than rods and are used for day and color vision. Color vision is mediated by cone photoreceptors that express cone-opsins with sensitivity peaks at different wavelengths (colors) of light. Humans have three cone types: short, mid and long wavelength sensitive cones (for simplicity, we will refer to these as blue, green and red cones, respectively). Rods and cones relay photic information through multisynaptic pathways to retinal ganglion cells (RGCs), which innervate different areas in the brain for complex visual processing13.A surprising discovery showed that a subpopulation of RGCs is intrinsically photosensitive and express the photopigment melanopsin. These cells were thus termed ipRGCs17–19. The melanopsin gene (Opn4) was originally cloned from Xenopus laevis dermal melanophores, and was shown to have orthologs in many mammalian species, including humans141. Sequence analysis shows that melanopsin shares more homology with invertebrate opsins than with vertebrate opsins, suggesting that melanopsin may use a different mechanism for light signaling than that used by the photopigments present in the rods and cones of vertebrates142. ipRGCs do not have modified membranes in which the photopigment can be concentrated: thus, melanopsin protein is expressed uniformly throughout the soma, dendrites, and the initial segment of the axon143. The lack of membrane specialization makes ipRGCs less sensitive to light than rods and cones. However, ipRGCs are able to incorporate light signals over extended period of time, resulting in an increase in their sensitivity during prolonged light stimulation. ipRGCs are most sensitive to wavelengths of light that are in the blue region of the light spectrum144, 145. As ganglion cells, ipRGCs also convey light information from rods and cones in addition to their intrinsic melanopsin-dependent pathway and can control a variety of light-mediated behaviors30.Originally, ipRGCs were thought to comprise a uniform population, however, recent discoveries revealed that ipRGCs are highly diverse, comprising at least five distinct subtypes (M1-M5) in rodents based on morphological and electrophysiological analyses22–29. The originally identified population is now known as M1 ipRGCs and project predominantly to brain regions involved in non-image forming visual functions, whereas the non-M1 ipRGCs show widespread projections to areas in the brain important for image formation. ipRGC subtypes express varying levels of the melanopsin protein and have different patterns of dendrite stratification in the inner plexiform layer (IPL)27, 28, 146, 147, indicating that each subtype could play a particular role in detecting light intrinsically and in signaling rod and cone information to the brain. PMID:24917305

Efficient generation of rat induced pluripotent stem cells using a non-viral inducible vector.

PubMed

Merkl, Claudia; Saalfrank, Anja; Riesen, Nathalie; Kühn, Ralf; Pertek, Anna; Eser, Stefan; Hardt, Markus Sebastian; Kind, Alexander; Saur, Dieter; Wurst, Wolfgang; Iglesias, Antonio; Schnieke, Angelika

2013-01-01

Current methods of generating rat induced pluripotent stem cells are based on viral transduction of pluripotency inducing genes (Oct4, Sox2, c-myc and Klf4) into somatic cells. These activate endogenous pluripotency genes and reprogram the identity of the cell to an undifferentiated state. Epigenetic silencing of exogenous genes has to occur to allow normal iPS cell differentiation. To gain more control over the expression of exogenous reprogramming factors, we used a novel doxycycline-inducible plasmid vector encoding Oct4, Sox2, c-Myc and Klf4. To ensure efficient and controlled generation of iPS cells by plasmid transfection we equipped the reprogramming vector with a bacteriophage φC31 attB site and used a φC31 integrase expression vector to enhance vector integration. A series of doxycycline-independent rat iPS cell lines were established. These were characterized by immunocytochemical detection of Oct4, SSEA1 and SSEA4, alkaline phosphatase staining, methylation analysis of the endogenous Oct4 promoter and RT-PCR analysis of endogenous rat pluripotency genes. We also determined the number of vector integrations and the extent to which reprogramming factor gene expression was controlled. Protocols were developed to generate embryoid bodies and rat iPS cells demonstrated as pluripotent by generating derivatives of all three embryonic germ layers in vitro, and teratoma formation in vivo. All data suggest that our rat iPS cells, generated by plasmid based reprogramming, are similar to rat ES cells. Methods of DNA transfection, protein transduction and feeder-free monolayer culture of rat iPS cells were established to enable future applications.

Mirror Observation of Finger Action Enhances Activity in Anterior Intraparietal Sulcus: A Functional Magnetic Resonance Imaging Study

PubMed Central

Murayama, Takashi; Takasugi, Jun; Monma, Masahiko; Oga, Masaru

2013-01-01

Mirror therapy can be used to promote recovery from paralysis in patients with post-stroke hemiplegia, There are a lot of reports that mirror-image observation of the unilateral moving hand enhanced the excitability of the primary motor area (M1) ipsilateral to the moving hand in healthy subjects. but the neural mechanisms underlying its therapeutic effects are currently unclear. To investigate this issue, we used functional magnetic resonance imaging to measure activity in brain regions related to visual information processing during mirror image movement observation. Thirteen healthy subjects performed a finger-thumb opposition task with the left and right hands separately, with or without access to mirror observation. In the mirror condition, one hand was reflected in a mirror placed above the abdomen in the MRI scanner. In the masked mirror condition, subjects performed the same task but with the mirror obscured. In both conditions, the other hand was held at rest behind the mirror. A between-task comparison (mirror versus masked mirror) revealed significant activation in the ipsilateral hemisphere in the anterior intraparietal sulcus (aIP) while performing all tasks, regardless of which hand was used. The right aIP was significantly activated while moving the right hand. In contrast, in the left aIP, a small number of voxels showed a tendency toward activation during both left and right hand movement. The enhancement of ipsilateral aIP activity by the mirror image observation of finger action suggests that bimodal aIP neurons can be activated by visual information. We propose that activation in the M1 ipsilateral to the moving hand can be induced by information passing through the ventral premotor area from the aIP. PMID:25792898

A multi-site randomised controlled trial of evidence-based supported employment for adults with severe and persistent mental illness.

PubMed

Waghorn, Geoffrey; Dias, Shannon; Gladman, Beverley; Harris, Meredith; Saha, Sukanta

2014-12-01

The Individual Placement and Support (IPS) approach is an evidence-based form of supported employment for people with severe and persistent mental illness. This approach is not yet widely available in Australia even though there is mounting evidence of its generalisability outside the USA. One previous Australian randomised controlled trial found that IPS is effective for young people with first episode psychosis. The aim of the current trial was to assess the effectiveness of evidence-based supported employment when implemented for Australian adult consumers of public mental health services by utilising existing service systems. A four-site randomised control trial design (n = 208) was conducted in Brisbane (two sites), Townsville and Cairns. The intervention consisted of an IPS supported employment service hosted by a community mental health team. The control condition was delivered at each site by mental health teams referring consumers to other disability employment services in the local area. At 12 months, those in the IPS condition had 2.4 times greater odds of commencing employment than those in the control condition (42.5% vs. 23.5%). The conditions did not differ on secondary employment outcomes including job duration, hours worked, or job diversity. Attrition was higher than expected in both conditions with 28.4% completing the baseline interview but taking no further part in the study. The results support previous international findings that IPS-supported employment is more effective than non-integrated supported employment. IPS can be successfully implemented this way in Australia, but with a loss of effect strength compared to previous USA trials. © 2014 Occupational Therapy Australia.

Role of peak current in conversion of patients with ventricular fibrillation.

PubMed

Anantharaman, Venkataraman; Wan, Paul Weng; Tay, Seow Yian; Manning, Peter George; Lim, Swee Han; Chua, Siang Jin Terrance; Mohan, Tiru; Rabind, Antony Charles; Vidya, Sudarshan; Hao, Ying

2017-07-01

Peak currents are the final arbiter of defibrillation in patients with ventricular fibrillation (VF). However, biphasic defibrillators continue to use energy in joules for electrical conversion in hopes that their impedance compensation properties will address transthoracic impedance (TTI), which must be overcome when a fixed amount of energy is delivered. However, optimal peak currents for conversion of VF remain unclear. We aimed to determine the role of peak current and optimal peak levels for conversion in collapsed VF patients. Adult, non-pregnant patients presenting with non-traumatic VF were included in the study. All defibrillations that occurred were included. Impedance values during defibrillation were used to calculate peak current values. The endpoint was return of spontaneous circulation (ROSC). Of the 197 patients analysed, 105 had ROSC. Characteristics of patients with and without ROSC were comparable. Short duration of collapse < 10 minutes correlated positively with ROSC. Generally, patients with average or high TTI converted at lower peak currents. 25% of patients with high TTI converted at 13.3 ± 2.3 A, 22.7% with average TTI at 18.2 ± 2.5 A and 18.6% with low TTI at 27.0 ± 4.7 A (p = 0.729). Highest peak current conversions were at < 15 A and 15-20 A. Of the 44 patients who achieved first-shock ROSC, 33 (75.0%) received < 20 A peak current vs. > 20 A for the remaining 11 (25%) patients (p = 0.002). For best effect, priming biphasic defibrillators to deliver specific peak currents should be considered. Copyright: © Singapore Medical Association

Role of peak current in conversion of patients with ventricular fibrillation

PubMed Central

Anantharaman, Venkataraman; Wan, Paul Weng; Tay, Seow Yian; Manning, Peter George; Lim, Swee Han; Chua, Siang Jin Terrance; Mohan, Tiru; Rabind, Antony Charles; Vidya, Sudarshan; Hao, Ying

2017-01-01

INTRODUCTION Peak currents are the final arbiter of defibrillation in patients with ventricular fibrillation (VF). However, biphasic defibrillators continue to use energy in joules for electrical conversion in hopes that their impedance compensation properties will address transthoracic impedance (TTI), which must be overcome when a fixed amount of energy is delivered. However, optimal peak currents for conversion of VF remain unclear. We aimed to determine the role of peak current and optimal peak levels for conversion in collapsed VF patients. METHODS Adult, non-pregnant patients presenting with non-traumatic VF were included in the study. All defibrillations that occurred were included. Impedance values during defibrillation were used to calculate peak current values. The endpoint was return of spontaneous circulation (ROSC). RESULTS Of the 197 patients analysed, 105 had ROSC. Characteristics of patients with and without ROSC were comparable. Short duration of collapse < 10 minutes correlated positively with ROSC. Generally, patients with average or high TTI converted at lower peak currents. 25% of patients with high TTI converted at 13.3 ± 2.3 A, 22.7% with average TTI at 18.2 ± 2.5 A and 18.6% with low TTI at 27.0 ± 4.7 A (p = 0.729). Highest peak current conversions were at < 15 A and 15–20 A. Of the 44 patients who achieved first-shock ROSC, 33 (75.0%) received < 20 A peak current vs. > 20 A for the remaining 11 (25%) patients (p = 0.002). CONCLUSION For best effect, priming biphasic defibrillators to deliver specific peak currents should be considered. PMID:28741007

Management of ATM-based networks supporting multimedia medical information systems

NASA Astrophysics Data System (ADS)

Whitman, Robert A.; Blaine, G. James; Fritz, Kevin; Goodgold, Ken; Heisinger, Patrick

1997-05-01

Medical information systems are acquiring the ability to collect and deliver many different types of medical information. In support of the increased network demands necessitated by these expanded capabilities, asynchronous transfer mode (ATM) based networks are being deployed in medical care systems. While ATM supplies a much greater line rate than currently deployed networks, the management and standards surrounding ATM are yet to mature. This paper explores the management and control issues surrounding an ATM network supporting medical information systems, and examines how management impacts network performance and robustness. A multivendor ATM network at the BJC Health System/Washington University and the applications using the network are discussed. Performance information for specific applications is presented and analyzed. Network management's influence on application reliability is outlined. The information collected is used to show how ATM network standards and management tools influence network reliability and performance. Performance of current applications using the ATM network is discussed. Special attention is given to issues encountered in implementation of hypertext transfer protocol over ATM internet protocol (IP) communications. A classical IP ATM implementation yields greater than twenty percent higher network performance over LANE. Maximum performance for a host's suite of applications can be obtained by establishing multiple individually engineered IP links through its ATM network connection.

[Induction of uridine 5'-diphosphate-glucuronosyltransferase gene expression by sulforaphane and its mechanism: experimental study in human colon cancel cells].

PubMed

Wang, Min; Li, Yan-Qing; Zhong, Ning; Chen, Jian; Xu, Xiao-Qun; Yuan, Meng-Biao

2005-03-30

To study the induction of expression of uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) 1A in colon cancer cells by sulforaphane (SFN) and its possible mechanism. Human colon cancer cells of the line Caco-2 were cultured and added with SFN of different terminal concentrations, all below the concentration of IC(50). RT-PCR was used to examine the expression of UGT1A mRNA induced by SFN. Western blotting was used to detect the expression of UGT1A protein. The glucuronidation rate of N-hydroxy-PhIP was measured by high performance liquid chromatography (HPLC). The nuclear localization of transcription factor Nrf2 was observed by confocal laser microscopy. (1) Expression of UGT1A mRNA was observed in the Cac0-2 cells induced by SFN of the concentrations of 10 micromol/L approximately 35 micromol/L in a dose-independent manner (P < 0.05). Sulforaphane of the concentration of 25 micromol/L induced the UGT1A mRNA expression time-dependently. The levels of UGT1A1, UGT1A8, and UGT1A10 mRNA expression were significantly increased in the cells treated with 25 micromol/L sulforaphane compared to that in the controls (P = 0.006, P = 0.017, and P = 0.008 respectively). (2) The UGT1A protein band intensity increased significantly in the Coco-2 cells treated with sulforaphane of the concentrations 10 micromol/L approximately 30 micromol/L for 24 h in comparison with the control cells. (3) When the microsomes from the untreated Caco-2 cells were incubated with N-hydroxy-PhIP there was a minor HPLC peak at the expected retention time for N-hydroxy-PhIP-N2-glucuronide. This peak was dramatically increased in the sulforaphane-treated cells, suggesting higher activities of glucuronidation of N-hydroxy-PhIP. (4) Cytoplasmic labeling of NF-E2-related factor 2 (Nrf2), a transcription factor, with no nuclear staining was observed in the non-stimulated cells, whereas an intense nuclear labeling was observed in the sulforaphane-treated cells, indicating the induction of nuclear translocation of Nrf2 by sulforaphane. (1) Low dose sulforaphane induces the expression of UGT1A, UGT1A1, UGT1A A8, and UGT1A A10 mRNA significantly. These changes are accompanied by an increase in UGT1A1 protein and increase in heterocyclic aromatic amine glucuronidation. (2) The induction of the phase II enzyme activity by SFN occurs at the transcriptional level and is regulated by Nrf2.

A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels.

PubMed

Maffie, Jonathon; Blenkinsop, Timothy; Rudy, Bernardo

2009-01-16

The channels mediating most of the somatodendritic A-type K(+) current in neurons are thought to be ternary complexes of Kv4 pore-forming subunits and two types of auxiliary subunits, the K(+) channel interacting proteins (KChIPs) and dipeptidyl-peptidase-like (DPPL) proteins. The channels expressed in heterologous expression systems by mixtures of Kv4.2, KChIP1 and DPP6-S resemble in many properties the A-type current in hippocampal CA1 pyramidal neurons and cerebellar granule cells, neurons with prominent A-type K(+) currents. However, the native currents have faster kinetics. Moreover, the A-type currents in neurons in intermediary layers of the superior colliculus have even faster inactivating rates. We have characterized a new DPP6 spliced isoform, DPP6-E, that produces in heterologous cells ternary Kv4 channels with very fast kinetics. DPP6-E is selectively expressed in a few neuronal populations in brain including cerebellar granule neurons, hippocampal pyramidal cells and neurons in intermediary layers of the superior colliculus. The effects of DPP6-E explain past discrepancies between reconstituted and native Kv4 channels in some neurons, and contributes to the diversity of A-type K(+) currents in neurons.

Ventolin Diskus and Inspyril Turbuhaler: an in vitro comparison.

PubMed

Broeders, M E A C; Molema, J; Burnell, P K P; Folgering, H T M

2005-01-01

Dose delivery (total emitted dose, or TED) from dry powder inhalers (DPIs), pulmonary deposition, and the biological effects depend on drug formulation and device and patient characteristics. The aim of this study was to measure, in vitro, the relationship between parameters of inhalation profiles recorded from patients, the TED and fine particle mass (FPM) of Diskus and Turbuhaler inhalers. Inhalation profiles (IPs) of 25 patients, a representative sample of a wide range of 1500 IPs generated by 10 stable asthmatics, 3 x 16 (mild/moderate/severe) COPD patients and 15 hospitalized patients with an exacerbation asthma or COPD, were selected for each device. These 25 IPs were input IPs for the Electronic Lung (a computerdriven inhalation simulator) to determine particle size distribution from Ventolin Diskus and Inspyril Turbuhaler. The TED and FPM of Diskus and FPM of Turbuhaler were affected by the peak inspiratory flow (PIF) and not by slope of the pressure-time curve, inhaled volume and inhalation time. This flow-dependency was more marked at lower flows (PIF < 40 L/min). Both the TED and FPM of Diskus were significantly higher as compared to those of the Turbuhaler [mean (SD) TED(_diskus) (%label claim) 83.5 (13.9) vs. TED(_turbuhaler) (72.5 (11.1) (p = 0.004), FPM(_diskus) (%label claim) 36.8 (9.8) vs FPM(_turbuhaler) (28.7 (7.7) (p < 0.05)]. The TED and FPM of Diskus and FPM of Turbuhaler were affected by PIF, the flow-dependency being greater at PIF values below 40 L/min. Lower PIFs occurred more often when using Turbuhaler than Diskus, since Turbuhaler have a higher resistivity, requires substantially higher pressure in order to generate the same flow as Diskus. TED, dose consistency and the FPM were higher for Diskus as compared to Turbuhaler. The flow dependency of TED and FPM was substantially influenced by inhalation profiles when not only profiles of the usual outpatient population were included but also the real outliers from exacerbated patients.

A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2.

PubMed

Lavik, Andrew R; Zhong, Fei; Chang, Ming-Jin; Greenberg, Edward; Choudhary, Yuvraj; Smith, Mitchell R; McColl, Karen S; Pink, John; Reu, Frederic J; Matsuyama, Shigemi; Distelhorst, Clark W

2015-09-29

Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP3Rs), inhibiting pro-apoptotic Ca2+ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP3R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP3 Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP3R interaction and thus inducing Ca2+-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton's tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP3R interaction.

ChIPBase: a database for decoding the transcriptional regulation of long non-coding RNA and microRNA genes from ChIP-Seq data.

PubMed

Yang, Jian-Hua; Li, Jun-Hao; Jiang, Shan; Zhou, Hui; Qu, Liang-Hu

2013-01-01

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) represent two classes of important non-coding RNAs in eukaryotes. Although these non-coding RNAs have been implicated in organismal development and in various human diseases, surprisingly little is known about their transcriptional regulation. Recent advances in chromatin immunoprecipitation with next-generation DNA sequencing (ChIP-Seq) have provided methods of detecting transcription factor binding sites (TFBSs) with unprecedented sensitivity. In this study, we describe ChIPBase (http://deepbase.sysu.edu.cn/chipbase/), a novel database that we have developed to facilitate the comprehensive annotation and discovery of transcription factor binding maps and transcriptional regulatory relationships of lncRNAs and miRNAs from ChIP-Seq data. The current release of ChIPBase includes high-throughput sequencing data that were generated by 543 ChIP-Seq experiments in diverse tissues and cell lines from six organisms. By analysing millions of TFBSs, we identified tens of thousands of TF-lncRNA and TF-miRNA regulatory relationships. Furthermore, two web-based servers were developed to annotate and discover transcriptional regulatory relationships of lncRNAs and miRNAs from ChIP-Seq data. In addition, we developed two genome browsers, deepView and genomeView, to provide integrated views of multidimensional data. Moreover, our web implementation supports diverse query types and the exploration of TFs, lncRNAs, miRNAs, gene ontologies and pathways.

[UTP regulates spontaneous transient outward currents in porcine coronary artery smooth muscle cells through PLC-IP(3) signaling pathway].

PubMed

Li, Peng-Yun; Zeng, Xiao-Rong; Yang, Yan; Cai, Fang; Li, Miao-Ling; Liu, Zhi-Fei; Pei, Jie; Zhou, Wen

2008-02-25

The aim of the present study was to investigate the effects of inositol 1,4,5-trisphosphate (IP(3))-generating agonist UTP on spontaneous transient outward currents (STOCs), and explore the role of intracellular Ca(2+) release in the current response mediated by IP(3) in porcine coronary artery smooth muscle cells (CASMCs). The coronary artery was excised from the fresh porcine heart and cut into small segments (2 mm × 5 mm) and then transferred to enzymatic dissociation solution for incubation. Single CASMCs were obtained by two-step enzyme digestion at 37 °C. STOCs were recorded and characterized using the perforated whole-cell patch-clamp configuration in freshly isolated porcine CASMCs. The currents were amplified and filtered by patch-clamp amplifier (Axopatch 200B), and then the digitized data were recorded by pClamp 9.0 software and further analyzed by MiniAnalysis 6.0 program. The results were as follows: (1) UTP led to conspicuous increases in STOC amplitude by (57.54±5.34)% and in frequency by (77.46±8.42)% (P<0.01, n=38). (2) The specific blocker of phospholipase C (PLC) - U73122 (5 μmol/L) remarkably reduced STOC amplitude by (31.04±7.46)% and frequency by (41.65±16.59)%, respectively (P<0.05, n=10). In the presence of U73122, UTP failed to reactivate STOCs (n=7). (3) Verapamil (20 μmol/L) and CdCl2 (200 μmol/L), two blockers of L-type voltage-dependent Ca(2+) channels, had little effects on STOCs initiated by UTP (n=8). (4) 1 μmol/L bisindolylmaleimide I (BisI), a potent blocker of protein kinase C (PKC), significantly increased STOC amplitude by (65.44±24.66)% and frequency by (61.35±21.47)% (P<0.01, n=12); UTP (40 μmol/L), applied in the presence of 1 μmol/L BisI, could further increase STOC activity (P<0.05, P<0.01, n=12). Subsequent application of ryanodine (50 μmol/L) abolished STOC activity. (5) In the presence of UTP (40 μmol/L), inhibition of IP(3) receptors (IP(3)Rs) by 2-aminoethoxydiphenyl borate (2-APB, 40 μmol/L) reduced STOC amplitude by (24.08±3.97)% (P<0.05, n=8), but had little effect on STOC frequency (n=8). While application of 2-APB (80 μmol/L) significantly reduced STOC amplitude by (31.43±6.34)% and frequency by (40.59±19.01)%, respectively (P<0.05, P<0.01, n=6). Subsequent application of ryanodine (50 μmol/L) completely blocked STOC activity. Pretreatment of cells with 2-APB (40 μmol/L) or ryanodine (50 μmol/L), UTP (40 μmol/L) failed to reactivate STOCs. The results suggest that UTP activates STOCs mainly via PLC and IP(3)-dependent mechanisms. Complex Ca(2+)-mobilization pathways are involved in UTP-mediated STOC activation in porcine CASMCs.

Average current is better than peak current as therapeutic dosage for biphasic waveforms in a ventricular fibrillation pig model of cardiac arrest.

PubMed

Chen, Bihua; Yu, Tao; Ristagno, Giuseppe; Quan, Weilun; Li, Yongqin

2014-10-01

Defibrillation current has been shown to be a clinically more relevant dosing unit than energy. However, the effects of average and peak current in determining shock outcome are still undetermined. The aim of this study was to investigate the relationship between average current, peak current and defibrillation success when different biphasic waveforms were employed. Ventricular fibrillation (VF) was electrically induced in 22 domestic male pigs. Animals were then randomized to receive defibrillation using one of two different biphasic waveforms. A grouped up-and-down defibrillation threshold-testing protocol was used to maintain the average success rate of 50% in the neighborhood. In 14 animals (Study A), defibrillations were accomplished with either biphasic truncated exponential (BTE) or rectilinear biphasic waveforms. In eight animals (Study B), shocks were delivered using two BTE waveforms that had identical peak current but different waveform durations. Both average and peak currents were associated with defibrillation success when BTE and rectilinear waveforms were investigated. However, when pathway impedance was less than 90Ω for the BTE waveform, bivariate correlation coefficient was 0.36 (p=0.001) for the average current, but only 0.21 (p=0.06) for the peak current in Study A. In Study B, a high defibrillation success (67.9% vs. 38.8%, p<0.001) was observed when the waveform delivered more average current (14.9±2.1A vs. 13.5±1.7A, p<0.001) while keeping the peak current unchanged. In this porcine model of VF, average current was better than peak current to be an adequate parameter to describe the therapeutic dosage when biphasic defibrillation waveforms were used. The institutional protocol number: P0805. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A

PubMed Central

Sundström, Karin B.; Nguyen Hoang, Anh Thu; Gupta, Shawon; Ahlm, Clas; Svensson, Mattias; Klingström, Jonas

2016-01-01

Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7–10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL-8, IP-10, and VEGF-A that peaked 20–25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS. PMID:26907493

Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A.

PubMed

Sundström, Karin B; Nguyen Hoang, Anh Thu; Gupta, Shawon; Ahlm, Clas; Svensson, Mattias; Klingström, Jonas

2016-01-01

Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7-10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL-8, IP-10, and VEGF-A that peaked 20-25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS.

A High Peak Current Source for the CEBAF Injector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yunn, Byung; Sinclair, Charles; Krafft, Geoffrey

1992-07-01

The CEBAF accelerator can drive high power IR and UV FELs, if a high peak current source is added to the existing front end. We present a design for a high peak current injector which is compatible with simultaneous operation of the accelerator for cw nulear physics (NP) beam. The high peak current injector provides 60 A peak current in 2 psec long bunches carrying 120 pC charge at 7.485 MHz. At 10 MeV that beam is combined with 5 MeV NP beam (0.13pC, 2 psec long bunches at 1497 MHz) in an energy combination chicane for simultaneous acceleration inmore » the injector linac. The modifications to the low-energy NP transport are described. Results of optical and beam dynamics calculations for both high peak current and NP beams in combined operation are presented.« less

Social leverage of intellectual property: road to the development of better therapy for tuberculosis.

PubMed

Thangaraj, Harry; Reljic, Rajko

2009-06-01

Current TB drug development is beset with many problems. There is a perceived lack of commercial return on investment, as the vast majority of TB patients come from impoverished areas of the world. Clinical trials for new TB drugs are complex, protracted and very expensive. Therefore, the development of new anti-tuberculosis drugs requires simultaneous forward planning of the design of the trials that will be required for licensing purposes. In this article we briefly review the current state of new TB drug development and discuss issues related to intellectual property (IP), with a special emphasis on how IP can facilitate rather than hinder the development of better TB drugs. We also list and discuss the major patent applications that underpin TB drugs that have entered prominent clinical trials and additional applications that were filed over the last five years for drugs resulting from basic upstream research.

Reproductive ecology of Vipera latastei, in the Iberian Peninsula: implications for the conservation of a Mediterranean viper.

PubMed

Pleguezuelos, Juan Manuel; Santos, Xavier; Brito, José Carlos; Parellada, Xavier; Llorente, Gustavo Adolfo; Fahd, Soumia

2007-01-01

Eurosiberian vipers have been considered model organisms, and studies on their reproductive ecology have afforded much of the current knowledge concerning viviparity in snakes. However, such studies are biased towards northern species and there is little information on Mediterranean species and/or populations. The reproductive ecology of Vipera latastei in the Iberian Peninsula was studied by analysing a large sample of specimens from collections, to better understand the conservation status of this Mediterranean viper. Males and females matured at small and similar body sizes (240 and 265 mm snout-vent length, respectively) and reproductive cycles in both sexes were seasonal. Spermatogenesis peaked in August, vitellogenesis developed in spring and the timing of the mating period was puzzling, with populations mating in autumn, spring, or in both seasons. The most striking finding was that adult females reproduced triennially on average. Lataste's viper is currently in continuous decline in the IP, and most of its populations are isolated in Mediterranean mountains. We hypothesize that prey scarcity and the brevity of the activity period in mountain habitats diminishes the ability of vipers to recover over the short term the energy expended in reproduction. The species needs 2 years for the acquisition and storage of energy ("capital breeder"), and a third year for the expenditure of this energy (in vitellogenesis and embryogenesis), a year during which females feed consistently ("income breeder"). Thus, this viper combines both strategies to supply the reproductive energy cost. Current decline in population and distribution, together with a poor capacity to renew populations, renders Lataste's viper vulnerable to environmental stochasticity.

Subtype-selective regulation of IP(3) receptors by thimerosal via cysteine residues within the IP(3)-binding core and suppressor domain.

PubMed

Khan, Samir A; Rossi, Ana M; Riley, Andrew M; Potter, Barry V L; Taylor, Colin W

2013-04-15

IP(3)R (IP(3) [inositol 1,4,5-trisphosphate] receptors) and ryanodine receptors are the most widely expressed intracellular Ca(2+) channels and both are regulated by thiol reagents. In DT40 cells stably expressing single subtypes of mammalian IP(3)R, low concentrations of thimerosal (also known as thiomersal), which oxidizes thiols to form a thiomercurylethyl complex, increased the sensitivity of IP(3)-evoked Ca(2+) release via IP(3)R1 and IP(3)R2, but inhibited IP(3)R3. Activation of IP(3)R is initiated by IP(3) binding to the IBC (IP(3)-binding core; residues 224-604) and proceeds via re-arrangement of an interface between the IBC and SD (suppressor domain; residues 1-223). Thimerosal (100 μM) stimulated IP(3) binding to the isolated NT (N-terminal; residues 1-604) of IP(3)R1 and IP(3)R2, but not to that of IP(3)R3. Binding of a competitive antagonist (heparin) or partial agonist (dimeric-IP(3)) to NT1 was unaffected by thiomersal, suggesting that the effect of thimerosal is specifically related to IP(3)R activation. IP(3) binding to NT1 in which all cysteine residues were replaced by alanine was insensitive to thimerosal, so too were NT1 in which cysteine residues were replaced in either the SD or IBC. This demonstrates that thimerosal interacts directly with cysteine in both the SD and IBC. Chimaeric proteins in which the SD of the IP(3)R was replaced by the structurally related A domain of a ryanodine receptor were functional, but thimerosal inhibited both IP(3) binding to the chimaeric NT and IP(3)-evoked Ca(2+) release from the chimaeric IP(3)R. This is the first systematic analysis of the effects of a thiol reagent on each IP(3)R subtype. We conclude that thimerosal selectively sensitizes IP(3)R1 and IP(3)R2 to IP(3) by modifying cysteine residues within both the SD and IBC and thereby stabilizing an active conformation of the receptor.

Distribution of voltage-dependent and intracellular Ca2+ channels in submucosal neurons from rat distal colon.

PubMed

Rehn, Matthias; Bader, Sandra; Bell, Anna; Diener, Martin

2013-09-01

We recently observed a bradykinin-induced increase in the cytosolic Ca2+ concentration in submucosal neurons of rat colon, an increase inhibited by blockers of voltage-dependent Ca2+ (Ca(v)) channels. As the types of Ca(v) channels used by this part of the enteric nervous system are unknown, the expression of various Ca(v) subunits has been investigated in whole-mount submucosal preparations by immunohistochemistry. Submucosal neurons, identified by a neuronal marker (microtubule-associated protein 2), are immunoreactive for Ca(v)1.2, Ca(v)1.3 and Ca(v)2.2, expression being confirmed by reverse transcription plus the polymerase chain reaction. These data agree with previous observations that the inhibition of L- and N-type Ca2+ currents strongly inhibits the response to bradykinin. However, whole-cell patch-clamp experiments have revealed that bradykinin does not enhance Ca2+ inward currents under voltage-clamp conditions. Consequently, bradykinin does not directly interact with Ca(v) channels. Instead, the kinin-induced Ca2+ influx is caused indirectly by the membrane depolarization evoked by this peptide. As intracellular Ca2+ channels on Ca(2+)-storing organelles can also contribute to Ca2+ signaling, their expression has been investigated by imaging experiments and immunohistochemistry. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) have been functionally demonstrated in submucosal neurons loaded with the Ca(2+)-sensitive fluorescent dye, fura-2. Histamine, a typical agonist coupled to the phospholipase C pathway, induces an increase in the fura-2 signal ratio, which is suppressed by 2-aminophenylborate, a blocker of IP3 receptors. The expression of IP3R1 has been confirmed by immunohistochemistry. In contrast, ryanodine, tested over a wide concentration range, evokes no increase in the cytosolic Ca2+ concentration nor is there immunohistochemical evidence for the expression of ryanodine receptors in these neurons. Thus, rat submucosal neurons are equipped with various types of high-voltage activated Ca(v) channels and with IP3 receptors for intracellular Ca2+ signaling.

The Inner Magnetosphere Plasma Response to Interplanetary Shocks: Van Allen Probes HOPE Observations

NASA Astrophysics Data System (ADS)

Winter, L. M.; Denton, M.; Ferradas, C.; Henderson, M. G.; Larsen, B.; Reeves, G.; Skoug, R. M.; Thomsen, M. F.

2017-12-01

The Van Allen Probes' Helium, Oxygen, Proton, and Electron (HOPE) sensors measure ion and electron populations in the plasmasphere, plasma sheet, and lower-energy ring current, providing unique observations at low energies (0.001-50 keV) and low L-shell (down to 1.5 RE). We use the capabilities of these two spacecraft to probe changes in the low energy particles in response to interplanetary (IP) shocks. We focus on changes in the plasma energies, composition, and pitch angle distributions following IP shocks and storm sudden commencements from 2012-2017 through a comparison of HOPE observations preceding and post shock.

Client/Server data serving for high performance computing

NASA Technical Reports Server (NTRS)

Wood, Chris

1994-01-01

This paper will attempt to examine the industry requirements for shared network data storage and sustained high speed (10's to 100's to thousands of megabytes per second) network data serving via the NFS and FTP protocol suite. It will discuss the current structural and architectural impediments to achieving these sorts of data rates cost effectively today on many general purpose servers and will describe and architecture and resulting product family that addresses these problems. The sustained performance levels that were achieved in the lab will be shown as well as a discussion of early customer experiences utilizing both the HIPPI-IP and ATM OC3-IP network interfaces.

Startle potentiation to uncertain threat as a psychophysiological indicator of fear-based psychopathology: An examination across multiple internalizing disorders.

PubMed

Gorka, Stephanie M; Lieberman, Lynne; Shankman, Stewart A; Phan, K Luan

2017-01-01

Heightened reactivity to uncertain threat (U-threat) is an important individual difference factor that may characterize fear-based internalizing psychopathologies (IPs) and distinguish them from distress/misery IPs. To date, however, the majority of existing research examining reactivity to U-threat has been within individuals with panic disorder and major depressive disorder (MDD) and no prior study has directly tested this hypothesis across multiple IPs. The current study therefore explored whether heightened reactivity to U-threat is a psychophysiological indicator of fear-based psychopathology across 5 groups: current (a) social anxiety disorder (SAD); (b) specific phobia (SP); (c) generalized anxiety disorder (GAD); (d) MDD; and (c) individuals with no history of psychopathology (controls). All 160 adults completed a well-validated threat-of-shock task designed to probe responses to predictable (P-) and U-threat. Startle eyeblink potentiation was recorded as an index of aversive arousal. Results indicated that individuals with SAD and SP evidenced greater startle potentiation to U-threat, but not P-threat, relative to individuals with GAD, MDD, and controls (who did not differ). The current findings, along with the prior panic disorder and MDD literature, suggest that heightened reactivity to U-threat is a psychophysiological indicator of fear-based disorders and could represent a neurobiological organizing principle for internalizing psychopathology. The findings also suggest that individuals with fear disorders generally display a hypersensitivity to uncertain aversive events, which could contribute to their psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Survey of heating and current drive for K-DEMO

NASA Astrophysics Data System (ADS)

Mikkelsen, D. R.; Kessel, C. E.; Poli, F. M.; Bertelli, N.; Kim, K.

2018-03-01

We present calculations of heating and current drive by neutral injection and by electromagnetic waves in the ion cyclotron, helicon, lower hybrid, and electron cyclotron frequency ranges for the steady state burn conditions in a K-DEMO configuration with I_p=12.3 MA, a  =  2.1 m, R_o=6.8 m, B_o=7.4 T, \

Parameters of triggered-lightning flashes in Florida and Alabama

NASA Astrophysics Data System (ADS)

Fisher, R. J.; Schnetzer, G. H.; Thottappillil, R.; Rakov, V. A.; Uman, M. A.; Goldberg, J. D.

1993-12-01

Channel base currents from triggered lightning were measured at the NASA Kennedy Space Center, Florida, during summer 1990 and at Fort McClellan, Alabama, during summer 1991. Additionally, 16-mm cinematic records with 3- or 5-ms resolution were obtained for all flashes, and streak camera records were obtained for three of the Florida flashes. The 17 flashes analyzed here contained 69 strokes, all lowering negative charge from cloud to ground. Statistics on interstroke interval, no-current interstroke interval, total stroke duration, total stroke charge, total stroke action integral (∫ i2dt), return stroke current wave front characteristics, time to half peak value, and return stroke peak current are presented. Return stroke current pulses, characterized by rise times of the order of a few microseconds or less and peak values in the range of 4 to 38 kA, were found not to occur until after any preceding current at the bottom of the lightning channel fell below the noise level of less than 2 A. Current pulses associated with M components, characterized by slower rise times (typically tens to hundreds of microseconds) and peak values generally smaller than those of the return stroke pulses, occurred during established channel current flow of some tens to some hundreds of amperes. A relatively strong positive correlation was found between return stroke current average rate of rise and current peak. There was essentially no correlation between return stroke current peak and 10-90% rise time or between return stroke peak and the width of the current waveform at half of its peak value. Parameters of the lightning flashes triggered in Florida and Alabama are similar to each other but are different from those of triggered lightning recorded in New Mexico during the 1981 Thunderstorm Research International Program. Continuing currents that follow return stroke current peaks and last for more than 10 ms exhibit a variety of wave shapes that we have subdivided into four categories. All such continuing currents appear to start with a current pulse presumably associated with an M component. A brief summary of lightning parameters important for lightning protection, in a form convenient for practical use, is presented in an appendix.

Synaptically activated Ca2+ waves in layer 2/3 and layer 5 rat neocortical pyramidal neurons

PubMed Central

Larkum, Matthew E; Watanabe, Shigeo; Nakamura, Takeshi; Lasser-Ross, Nechama; Ross, William N

2003-01-01

Calcium waves in layer 2/3 and layer 5 neocortical somatosensory pyramidal neurons were examined in slices from 2- to 8-week-old rats. Repetitive synaptic stimulation evoked a delayed, all-or-none [Ca2+]i increase primarily on the main dendritic shaft. This component was blocked by 1 mm (R,S)-α-methyl-4-carboxyphenylglycine (MCPG), 10 μm ryanodine, 1 mg ml−1 internal heparin, and was not blocked by 400 μm internal Ruthenium Red, indicating that it was due to Ca2+ release from internal stores by inositol 1,4,5-trisphosphate (IP3) mobilized via activation of metabotropic glutamate receptors. Calcium waves were initiated on the apical shaft at sites between the soma to around the main branch point, mostly at insertion points of oblique dendrites, and spread in both directions along the shaft. In the proximal dendrites the peak amplitude of the resulting [Ca2+]i change was much larger than that evoked by a train of Na+ spikes. In distal dendrites the peak amplitude was comparable to the [Ca2+]i change due to a Ca2+ spike. IP3-mediated Ca2+ release also was observed in the presence of the metabotropic agonists t-ACPD and carbachol when backpropagating spikes were generated. Ca2+ entry through NMDA receptors was observed primarily on the oblique dendrites. The main differences between waves in neocortical neurons and in previously described hippocampal pyramidal neurons were, (a) Ca2+ waves in L5 neurons could be evoked further out along the main shaft, (b) Ca2+ waves extended slightly further out into the oblique dendrites and (c) higher concentrations of bath-applied t-ACPD and carbachol were required to generate Ca2+ release events by backpropagating action potentials. PMID:12692172

Acute exposure to cadmium induces prolonged neutrophilia along with delayed induction of granulocyte colony-stimulating factor in the livers of mice.

PubMed

Horiguchi, Hyogo; Oguma, Etsuko

2016-12-01

Acute exposure to cadmium (Cd), a toxic heavy metal, causes systemic inflammation characterized by neutrophilia. To elucidate the mechanism of neutrophilia induced by Cd, we investigated the induction of granulocyte colony-stimulating factor (G-CSF), which regulates neutrophil production, in mice with acute Cd toxicity, and compared it with mice injected with lipopolysaccharide (LPS) as an inducer of general inflammatory responses. We injected BALB/c mice with Cd at 2.5 mg/kg i.p. or LPS at 0.5 mg/kg i.p. and sampled the peripheral blood and organs at time points up to 24 h. In Cd-treated mice, the peripheral neutrophil count increased steadily up to 24 h, whereas LPS-treated mice showed a more rapid increase with a peak at 12 h. The serum G-CSF level increased gradually to reach a plateau at 12-18 h in Cd-treated mice, but LPS-treated mice showed a marked increase, reaching a peak at 2-3 h. A gradual elevation of G-CSF mRNA expression up to 24 h was detected by real-time PCR in the livers of Cd-treated mice, but in LPS-treated mice its highest expression was observed in the liver with a rapid increase at 2 h. By in situ hybridization using G-CSF RNA probes, hepatic Kupffer cells were identified as G-CSF-producing cells in the liver. These results indicated that Cd has a characteristic effect of delayed induction of G-CSF in the liver, causing systemic inflammation accompanied by prolonged neutrophilia.

Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors

PubMed Central

Oka, Takakazu; Oka, Kae; Kobayashi, Takuya; Sugimoto, Yukihiko; Ichikawa, Atsushi; Ushikubi, Fumitaka; Narumiya, Shuh; Saper, Clifford B

2003-01-01

Previous studies have disagreed about whether prostaglandin EP1 or EP3 receptors are critical for producing febrile responses. We therefore injected lipopolysaccharide (LPS) at a variety doses (1 μg kg−1−1 mg kg−1) intraperitoneally (I.P.) into wild-type (WT) mice and mice lacking the EP1 or the EP3 receptors and measured changes in core temperature (Tc) by using telemetry. In WT mice, I.P. injection of LPS at 10 μg kg−1 increased Tc about 1 °C, peaking 2 h after injection. At 100 μg kg−1, LPS increased Tc, peaking 5–8 h after injection. LPS at 1 mg kg−1 decreased Tc, reaching a nadir at 5–8 h after injection. In EP1 receptor knockout (KO) mice injected with 10 μg kg−1 LPS, only the initial (< 40 min) increase in Tc was lacking; with 100 μg kg−1 LPS the mice showed no febrile response. In EP3 receptor KO mice, LPS decreased Tc in a dose- and time-dependent manner. Furthermore, in EP3 receptor KO mice subcutaneous injection of turpentine did not induce fever. Both EP1 and EP3 receptor KO mice showed a normal circadian cycle of Tc and brief hyperthermia following psychological stress (cage-exchange stress and buddy-removal stress). The present study suggests that both the EP1 and the EP3 receptors play a role in fever induced by systemic inflammation but neither EP receptor is involved in the circadian rise in Tc or psychological stress-induced hyperthermia in mice. PMID:12837930

ISS and STS Commercial Off-the-Shelf Router Testing

NASA Technical Reports Server (NTRS)

Ivancie, William D.; Bell, Terry L.; Shell, Dan

2002-01-01

This report documents the results of testing performed with commercial off-the-shelf (COTS) routers and Internet Protocols (IPs) to determine if COTS equipment and IP could be utilized to upgrade NASA's current Space Transportation System (STS), the Shuttle, and the International Space Station communication infrastructure. Testing was performed by NASA Glenn Research Center (GRC) personnel within the Electronic Systems Test Laboratory (ESTE) with cooperation from the Mission Operations Directorate (MOD) Qualification and Utilization of Electronic System Technology (QUEST) personnel. The ESTE testing occurred between November 1 and 9, 2000. Additional testing was performed at NASA Glenn Research Center in a laboratory environment with equipment configured to emulate the STS. This report documents those tests and includes detailed test procedures, equipment interface requirements, test configurations and test results. The tests showed that a COTS router and standard Transmission Control Protocols and Internet Protocols (TCP/IP) could be used for both the Shuttle and the Space Station if near-error-free radio links are provided.

Approaches to eliminate waste and reduce cost for recycling glass.

PubMed

Chao, Chien-Wen; Liao, Ching-Jong

2011-12-01

In recent years, the issue of environmental protection has received considerable attention. This paper adds to the literature by investigating a scheduling problem in the manufacturing of a glass recycling factory in Taiwan. The objective is to minimize the sum of the total holding cost and loss cost. We first represent the problem as an integer programming (IP) model, and then develop two heuristics based on the IP model to find near-optimal solutions for the problem. To validate the proposed heuristics, comparisons between optimal solutions from the IP model and solutions from the current method are conducted. The comparisons involve two problem sizes, small and large, where the small problems range from 15 to 45 jobs, and the large problems from 50 to 100 jobs. Finally, a genetic algorithm is applied to evaluate the proposed heuristics. Computational experiments show that the proposed heuristics can find good solutions in a reasonable time for the considered problem. Copyright © 2011 Elsevier Ltd. All rights reserved.

ELRIS2D: A MATLAB Package for the 2D Inversion of DC Resistivity/IP Data

NASA Astrophysics Data System (ADS)

Akca, Irfan

2016-04-01

ELRIS2D is an open source code written in MATLAB for the two-dimensional inversion of direct current resistivity (DCR) and time domain induced polarization (IP) data. The user interface of the program is designed for functionality and ease of use. All available settings of the program can be reached from the main window. The subsurface is discre-tized using a hybrid mesh generated by the combination of structured and unstructured meshes, which reduces the computational cost of the whole inversion procedure. The inversion routine is based on the smoothness constrained least squares method. In order to verify the program, responses of two test models and field data sets were inverted. The models inverted from the synthetic data sets are consistent with the original test models in both DC resistivity and IP cases. A field data set acquired in an archaeological site is also used for the verification of outcomes of the program in comparison with the excavation results.

Efficient eNB inter-communication scheme in converged mobile and NG-PON2 system

NASA Astrophysics Data System (ADS)

Xiao, Simiao; Sun, Xiao; Zhang, Kaibin

2016-02-01

In LTE, a new X2-interface is defined to facilitate direct communication between neighboring eNBs. Since LTE is an all-IP network, the X2-interface traffic currently needs to be routed and transponded in L3 at the edge router by IP addressing. As mobile data increases, it is a promising trend to backhaul mobile services based on PON. In this paper, an effective approach for eNB inter-communication over TWDM-PON is proposed. By associating the IP address of eNB and the MAC address of ONU, the "inter-eNB communication in L3" can be mapped into "inter-ONU communication in L2" and transponded via the protocol of PON at the OLT. Thus, fast and cost-effective eNB inter-communication can be realized based on TWDM-PON within one wavelength channel and between different wavelength channels. The increasing data traffic pressure to the core network can also be alleviated.

Classifier fusion for VoIP attacks classification

NASA Astrophysics Data System (ADS)

Safarik, Jakub; Rezac, Filip

2017-05-01

SIP is one of the most successful protocols in the field of IP telephony communication. It establishes and manages VoIP calls. As the number of SIP implementation rises, we can expect a higher number of attacks on the communication system in the near future. This work aims at malicious SIP traffic classification. A number of various machine learning algorithms have been developed for attack classification. The paper presents a comparison of current research and the use of classifier fusion method leading to a potential decrease in classification error rate. Use of classifier combination makes a more robust solution without difficulties that may affect single algorithms. Different voting schemes, combination rules, and classifiers are discussed to improve the overall performance. All classifiers have been trained on real malicious traffic. The concept of traffic monitoring depends on the network of honeypot nodes. These honeypots run in several networks spread in different locations. Separation of honeypots allows us to gain an independent and trustworthy attack information.

Promising practices in vocational services for the community reintegration of returning veterans: The individual placement and support model and beyond.

PubMed

Wewiorski, Nancy J; Gorman, Jay A; Scoglio, Arielle A J; Fukuda, Seiya; Reilly, Erin; Mueller, Lisa; O'Connor, Maureen; Penk, Walter E; Drebing, Charles E

2018-05-01

Supporting returning veterans' job-seeking, hiring, and retention issues has become an essential goal for effective community reintegration. Given both the particular strengths and challenges associated with veterans transitioning from military to civilian life, multiple models for supported employment have become integrated into Veterans Affairs health care facilities across the nation. In this article, we review the state of vocational rehabilitation for veterans, with a particular focus on individual placement and support-supported employment (IPS-SE), the current vocational services model that is considered the gold standard of vocational rehabilitation. Various modifications to the IPS-SE model are presented, including additions such as cognitive rehabilitation, contingency management, motivational interviewing, supported self-employment, and transitional work. Finally, recommendations are made about future directions and strategies to expand access to IPS-SE-based programs and to effectively meet the needs of returning veterans for employment in jobs of their choice. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Securing Real-Time Sessions in an IMS-Based Architecture

NASA Astrophysics Data System (ADS)

Cennamo, Paolo; Fresa, Antonio; Longo, Maurizio; Postiglione, Fabio; Robustelli, Anton Luca; Toro, Francesco

The emerging all-IP mobile network infrastructures based on 3rd Generation IP Multimedia Subsystem philosophy are characterised by radio access technology independence and ubiquitous connectivity for mobile users. Currently, great focus is being devoted to security issues since most of the security threats presently affecting the public Internet domain, and the upcoming ones as well, are going to be suffered by mobile users in the years to come. While a great deal of research activity, together with standardisation efforts and experimentations, is carried out on mechanisms for signalling protection, very few integrated frameworks for real-time multimedia data protection have been proposed in a context of IP Multimedia Subsystem, and even fewer experimental results based on testbeds are available. In this paper, after a general overview of the security issues arising in an advanced IP Multimedia Subsystem scenario, a comprehensive infrastructure for real-time multimedia data protection, based on the adoption of the Secure Real-Time Protocol, is proposed; then, the development of a testbed incorporating such functionalities, including mechanisms for key management and cryptographic context transfer, and allowing the setup of Secure Real-Time Protocol sessions is presented; finally, experimental results are provided together with quantitative assessments and comparisons of system performances for audio sessions with and without the adoption of the Secure Real-Time Protocol framework.

Systematic comparison of monoclonal versus polyclonal antibodies for mapping histone modifications by ChIP-seq.

PubMed

Busby, Michele; Xue, Catherine; Li, Catherine; Farjoun, Yossi; Gienger, Elizabeth; Yofe, Ido; Gladden, Adrianne; Epstein, Charles B; Cornett, Evan M; Rothbart, Scott B; Nusbaum, Chad; Goren, Alon

2016-01-01

The robustness of ChIP-seq datasets is highly dependent upon the antibodies used. Currently, polyclonal antibodies are the standard despite several limitations: They are non-renewable, vary in performance between lots and need to be validated with each new lot. In contrast, monoclonal antibody lots are renewable and provide consistent performance. To increase ChIP-seq standardization, we investigated whether monoclonal antibodies could replace polyclonal antibodies. We compared monoclonal antibodies that target five key histone modifications (H3K4me1, H3K4me3, H3K9me3, H3K27ac and H3K27me3) to their polyclonal counterparts in both human and mouse cells. Overall performance was highly similar for four monoclonal/polyclonal pairs, including when we used two distinct lots of the same monoclonal antibody. In contrast, the binding patterns for H3K27ac differed substantially between polyclonal and monoclonal antibodies. However, this was most likely due to the distinct immunogen used rather than the clonality of the antibody. Altogether, we found that monoclonal antibodies as a class perform equivalently to polyclonal antibodies for the detection of histone post-translational modifications in both human and mouse. Accordingly, we recommend the use of monoclonal antibodies in ChIP-seq experiments.

A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held

PubMed Central

Guo, Jun; Ge, Jian-long; Hao, Mei; Sun, Zhi-cheng; Wu, Xin-sheng; Zhu, Jian-bing; Wang, Wei; Yao, Pan-tong; Lin, Wei; Xue, Lei

2015-01-01

Although vesicle replenishment is critical in maintaining exo-endocytosis recycling, the underlying mechanisms are not well understood. Previous studies have shown that both rapid and slow endocytosis recycle into a very large recycling pool instead of within the readily releasable pool (RRP), and the time course of RRP replenishment is slowed down by more intense stimulation. This finding contradicts the calcium/calmodulin-dependence of RRP replenishment. Here we address this issue and report a three-pool model for RRP replenishment at a central synapse. Both rapid and slow endocytosis provide vesicles to a large reserve pool (RP) ~42.3 times the RRP size. When moving from the RP to the RRP, vesicles entered an intermediate pool (IP) ~2.7 times the RRP size with slow RP-IP kinetics and fast IP-RRP kinetics, which was responsible for the well-established slow and rapid components of RRP replenishment. Depletion of the IP caused the slower RRP replenishment observed after intense stimulation. These results establish, for the first time, a realistic cycling model with all parameters measured, revealing the contribution of each cycling step in synaptic transmission. The results call for modification of the current view of the vesicle recycling steps and their roles. PMID:25825223

Anorexia Induction by the Trichothecene Deoxynivalenol (Vomitoxin) Is Mediated by the Release of the Gut Satiety Hormone Peptide YY

PubMed Central

Pestka, James J.

2012-01-01

Consumption of deoxynivalenol (DON), a trichothecene mycotoxin known to commonly contaminate grain-based foods, suppresses growth of experimental animals, thus raising concerns over its potential to adversely affect young children. Although this growth impairment is believed to result from anorexia, the initiating mechanisms for appetite suppression remain unknown. Here, we tested the hypothesis that DON induces the release of satiety hormones and that this response corresponds to the toxin’s anorectic action. Acute ip exposure to DON had no effect on plasma glucagon-like peptide-1, leptin, amylin, pancreatic polypeptide, gastric inhibitory peptide, or ghrelin; however, the toxin was found to robustly elevate peptide YY (PYY) and cholecystokinin (CCK). Specifically, ip exposure to DON at 1 and 5mg/kg bw induced PYY by up to 2.5-fold and CCK by up to 4.1-fold. These responses peaked within 15–120min and lasted up to 120min (CCK) and 240min (PPY), corresponding with depressed rates of food intake. Direct administration of exogenous PYY or CCK similarly caused reduced food intake. Food intake experiments using the NPY2 receptor antagonist BIIE0246 and the CCK1A receptor antagonist devazepide, individually, suggested that PYY mediated DON-induced anorexia but CCK did not. Orolingual exposure to DON induced plasma PYY and CCK elevation and anorexia comparable with that observed for ip exposure. Taken together, these findings suggest that PYY might be one critical mediator of DON-induced anorexia and, ultimately, growth suppression. PMID:22903826

Fusion Research in Ioffe Institute

NASA Astrophysics Data System (ADS)

Askinazi, L. G.; Afanasyev, V. I.; Altukhov, A. B.; Bakharev, N. N.; Belokurov, A. A.; Bulanin, V. V.; Bykov, A. S.; Chernyshev, F. V.; Chugunov, I.; Dyachenko, V. V.; Esipov, L. A.; Gin, D.; Goncharov, P. R.; Gurchenko, A. D.; Gusakov, E. Z.; Gusev, V. K.; Heuraux, S.; Iblyaminova, A. D.; Irzak, M. A.; Kantor, M. Yu.; Kaveeva, E. G.; Kiviniemi, T.; Khilkevitch, E. M.; Khitrov, S. A.; Khromov, N. A.; Kornev, V. A.; Kouprienko, D. V.; Kurskiev, G. S.; Lashkul, S. I.; Lebedev, S. V.; Leerink, S.; Melnik, A. D.; Minaev, V. B.; Mironov, M. I.; Miroshnikov, I. V.; Mukhin, E. E.; Nesenevich, V. G.; Niskala, P.; Novokhatsky, A. N.; Patrov, M. I.; Perevalov, A. A.; Petrov, M. P.; Petrov, A. V.; Petrov, Yu. V.; Popov, A. Yu.; Rozhansky, V. A.; Rozhdestvenskiy, V. V.; Sakharov, N. V.; Saveliev, A. N.; Senichenkov, I. Yu.; Sergeev, V. Yu.; Shchegolev, P. B.; Shatalin, S. V.; Shcherbinin, O. N.; Shevelev, A. E.; Sidorov, A. V.; da Silva, F.; Smirnov, A. I.; Stepanov, A. Yu.; Sysoeva, E. V.; Teplova, N. V.; Tolstyakov, S. Yu.; Tukachinsky, A. S.; Varfolomeev, V. I.; Vekshina, E. O.; Vildjunas, M. I.; Voronin, A. V.; Voskoboinikov, S. P.; Wagner, F.; Yashin, A. Yu.; Zhubr, N. A.

2015-10-01

In this paper we present the fusion related activities of the Plasma Physics Division at the Ioffe Institute. The first experiments on lower hybrid current drive (LHCD) in a spherical tokamak performed at the Globus-M tokamak (R = 0.36 m, a = 0.24 m, Bt = 0.4 T, Ip = 200 kA) with a novel poloidally oriented grill resulted in an RF driven current of up to 30 kA at (100 kW, 2.5 GHz), exceeding the modelling predictions. At the FT-2 tokamak (R = 0.56 m, a = 0.08 m, Bt = 3 T, Ip = 30 kA) experiments with a traditional toroidally oriented grill revealed no strong dependence of the LHCD density limit on the H/D ratio in spite of LH resonance densities differing by a factor of 3. Microwave Doppler reflectometry (DR) at the Globus-M, and DR and heavy ion beam probe measurements at the tokamak TUMAN-3M (R = 0.53 m, a = 0.24 m, Bt = 1.0 T, Ip = 190 kA) demonstrated geodesic acoustic mode (GAM) suppression at the L to H transition. Observations at FT-2 using Doppler Enhanced Scattering showed that the GAM amplitude is anti-correlated both spatially and temporally to the drift turbulence level and electron thermal diffusivity. For the first time turbulence amplitude modulation at the GAM frequency was found both experimentally and in global gyrokinetic modelling. A model of the L-H transition is proposed based on this effect. The loss mechanisms of energetic ions' (EI) were investigated in the neutral beam injection (NBI) experiments on Globus-M and TUMAN-3M. Empirical scaling of the 2.45 MeV DD neutron rate for the two devices shows a strong dependence on toroidal field Bt1.29 and plasma current Ip1.34 justifying the Bt and Ip increase by a factor of 2.5 for the proposed upgrade of Globus-M. Bursts of ˜1 MHz Alfvenic type oscillations correlating with sawtooth crashes were observed in ohmic TUMAN-3M discharges. The possibility of low threshold parametric excitation of Bernstein and upper hybrid waves trapped in drift-wave eddies resulting in anomalous absorption in electron cyclotron resonance heating (ECRH) experiments in toroidal plasmas was identified theoretically. A novel method of radial correlation Doppler reflectometry is shown to be capable of measuring the turbulence wave-number spectrum in realistic 2D geometry. On the progress in design and fabrication of three diagnostics for ITER developed in the Ioffe institute is reported: neutral particle analysis, divertor Thomson scattering and gamma spectroscopy.

Electric conductivity for laboratory and field monitoring of induced partial saturation (IPS) in sands

NASA Astrophysics Data System (ADS)

Kazemiroodsari, Hadi

Liquefaction is loss of shear strength in fully saturated loose sands caused by build-up of excess pore water pressure, during moderate to large earthquakes, leading to catastrophic failures of structures. Currently used liquefaction mitigation measures are often costly and cannot be applied at sites with existing structures. An innovative, practical, and cost effective liquefaction mitigation technique titled "Induced Partial Saturation" (IPS) was developed by researchers at Northeastern University. The IPS technique is based on injection of sodium percarbonate solution into fully saturated liquefaction susceptible sand. Sodium percarbonate dissolves in water and breaks down into sodium and carbonate ions and hydrogen peroxide which generates oxygen gas bubbles. Oxygen gas bubbles become trapped in sand pores and therefore decrease the degree of saturation of the sand, increase the compressibility of the soil, thus reduce its potential for liquefaction. The implementation of IPS required the development and validation of a monitoring and evaluation technique that would help ensure that the sands are indeed partially saturated. This dissertation focuses on this aspect of the IPS research. The monitoring system developed was based on using electric conductivity fundamentals and probes to detect the transport of chemical solution, calculate degree of saturation of sand, and determine the final zone of partial saturation created by IPS. To understand the fundamentals of electric conductivity, laboratory bench-top tests were conducted using electric conductivity probes and small specimens of Ottawa sand. Bench-top tests were used to study rate of generation of gas bubbles due to reaction of sodium percarbonate solution in sand, and to confirm a theory based on which degree of saturation were calculated. In addition to bench-top tests, electric conductivity probes were used in a relatively large sand specimen prepared in a specially manufactured glass tank. IPS was implemented in the prepared specimen to validate the numerical simulation model and explore the use of conductivity probes to detect the transport of chemical solution, estimate degree of saturation achieved due to injection of chemical solution, and evaluate final zone of partial saturation. The conductivity probe and the simulation results agreed well. To study the effect of IPS on liquefaction response of the sand specimen, IPS was implemented in a large (2-story high) sand specimen prepared in the laminar box of NEES Buffalo and then the specimen was subjected to harmonic shaking. Electric conductivity probes were used in the specimen treatment by controlling the duration and spacing of injection of the chemical solution, in monitoring the transport of chemical solution, in the estimation of zone of partial saturation achieved, and in the estimation of degree of saturation achieved due to implementation of IPS. The conductivity probes indicated partial saturation of the specimen. The shaking tests results confirmed the partial saturation state of the sand specimen. In addition, to the laboratory works, electric conductivity probes were used in field implementation of IPS in a pilot test at the Wildlife Liquefaction Array (WLA) of NEES UCSB site. The conductivity probes in the field test helped decide the optimum injection pressure, the injection tube spacing, and the degree of saturation that could be achieved in the field. The various laboratory and field tests confirmed that electric conductivity and the probes devised and used can be invaluable in the implementation of IPS, by providing information regarding transport of the chemical solution, the spacing of injection tubes, duration of injection, and the zone and degree of partial saturation caused by IPS.

Energy attenuation performance of impact protection worn by motorcyclists in real-world crashes.

PubMed

Albanese, Bianca; Gibson, Tom; Whyte, Tom; Meredith, Lauren; Savino, Giovanni; de Rome, Liz; Baldock, Matthew; Fitzharris, Michael; Brown, Julie

2017-05-29

Laboratory studies have demonstrated that impact protectors (IP) used in motorcycle clothing can reduce fracture severities. While crash studies have reported IP are associated with reduced likelihood of soft tissue injury, there is little evidence of their effectiveness in reducing fracture likelihood. This discrepancy might be related to IP quality. There are mandatory requirements for IP supplied with protective clothing in Europe, but not elsewhere. This study examines the energy attenuation performance of IP used by Australian riders. IP were harvested from clothing worn by crashed riders admitted to hospital. The IP were examined and energy attenuation properties were determined using EN 1621-1 test procedures. Impact injury was identified from medical records and defined as fractures, dislocations, and avulsions that occurred following impact to the rider's shoulders, elbows, hips, and/or knees. Fisher's exact test was used to examine the relationship between meeting the EN 1621-1 energy attenuation requirements and impact injury. The association between the average and maximum transmitted force, and impact injury was examined using generalized estimating equations. Motorcycle riders were recruited as part of an in-depth crash study through three hospitals in New South Wales, Australia, between 2012 and 2014. Riders were interviewed, and engineers conducted site, vehicle, and clothing inspections. Clothing was collected, or identical garments were purchased. Clothing was inspected for 62 riders. Of these, 19 wore clothing incorporating 76 IP. Twenty-six of these were impacted in the crash event. Almost all impacted IP (96%) were CE marked, and most (83%) met Level 1 energy attenuation requirements of EN 1621-1 when tested. Of the 26 impacted IP, four were associated with impact injuries, including midshaft and distal clavicle fractures and a scapula and olecranon fracture. No associations between meeting EN 1621-1 requirements and impact injury were found (p = 0.5). There was no association between average force transmitted and impact injury (95% CI: 0.91-1.24); however, as maximum force transmitted increased, the odds of impact injury increased (95% CI: 1.01-1.2). These results indicate a high probability of impact injury at 50 kN, the limit of maximum transmitted force specified in EN 1621-1. The allowable transmitted force of EN 1621-1 may be too high to effectively reduce the probability of impact injury. This is not surprising, given human tolerance levels that are reported in literature. Reducing the force limit below the reported fracture tolerance limits might be difficult with current technology. However, there is scope to reduce the EN 1621-1 maximum limit of 50 kN transmitted force. A reduction in the maximum force limit would improve rider protection and appears feasible, as 77% of tested IP recorded a maximum force <35 kN. This level of transmitted force is estimated to be associated with <20% probability of impact injury. While the performance of IP available to Australian riders is not regulated, most IP was CE marked. The results indicate a significant association between maximum transmitted force, tested according to EN 1621-1 procedures, and impact injury. Further investigation of the EN 1621-1 requirements may be warranted. This work will interest those targeting protective equipment for motorcyclists as a mechanism for reducing injury to these vulnerable road users.

Subtype-selective regulation of IP3 receptors by thimerosal via cysteine residues within the IP3-binding core and suppressor domain

PubMed Central

Khan, Samir A.; Rossi, Ana M.; Riley, Andrew M.; Potter, Barry V. L.; Taylor, Colin W.

2013-01-01

IP3R (IP3 [inositol 1,4,5-trisphosphate] receptors) and ryanodine receptors are the most widely expressed intracellular Ca2+ channels and both are regulated by thiol reagents. In DT40 cells stably expressing single subtypes of mammalian IP3R, low concentrations of thimerosal (also known as thiomersal), which oxidizes thiols to form a thiomercurylethyl complex, increased the sensitivity of IP3-evoked Ca2+ release via IP3R1 and IP3R2, but inhibited IP3R3. Activation of IP3R is initiated by IP3 binding to the IBC (IP3-binding core; residues 224–604) and proceeds via re-arrangement of an interface between the IBC and SD (suppressor domain; residues 1–223). Thimerosal (100 μM) stimulated IP3 binding to the isolated NT (N-terminal; residues 1–604) of IP3R1 and IP3R2, but not to that of IP3R3. Binding of a competitive antagonist (heparin) or partial agonist (dimeric-IP3) to NT1 was unaffected by thiomersal, suggesting that the effect of thimerosal is specifically related to IP3R activation. IP3 binding to NT1 in which all cysteine residues were replaced by alanine was insensitive to thimerosal, so too were NT1 in which cysteine residues were replaced in either the SD or IBC. This demonstrates that thimerosal interacts directly with cysteine in both the SD and IBC. Chimaeric proteins in which the SD of the IP3R was replaced by the structurally related A domain of a ryanodine receptor were functional, but thimerosal inhibited both IP3 binding to the chimaeric NT and IP3-evoked Ca2+ release from the chimaeric IP3R. This is the first systematic analysis of the effects of a thiol reagent on each IP3R subtype. We conclude that thimerosal selectively sensitizes IP3R1 and IP3R2 to IP3 by modifying cysteine residues within both the SD and IBC and thereby stabilizing an active conformation of the receptor. PMID:23282150

Modeling ECCD/MHD coupling using NIMROD, GENRAY, and the Integrated Plasma Simulator

NASA Astrophysics Data System (ADS)

Jenkins, Thomas G.; Schnack, D. D.; Sovinec, C. R.; Hegna, C. C.; Callen, J. D.; Ebrahimi, F.; Kruger, S. E.; Carlsson, J.; Held, E. D.; Ji, J.-Y.; Harvey, R. W.; Smirnov, A. P.; Elwasif, W. R.

2009-11-01

We summarize ongoing theoretical/numerical work relevant to the development of a self--consistent framework for the inclusion of RF effects in fluid simulations; specifically, we consider the stabilization of resistive tearing modes in tokamak geometry by electron cyclotron current drive. In the fluid equations, ad hoc models for the RF--induced currents have previously been shown to shrink or altogether suppress the nonlinearly saturated magnetic islands generated by tearing modes; progress toward a self--consistent model is reported. The interfacing of the NIMROD [1] code with the GENRAY/CQL3D [2] codes (which calculate RF propagation and energy/momentum deposition) via the Integrated Plasma Simulator (IPS) framework [3] is explained, RF-induced rational surface motion and the equilibration of RF--induced currents over plasma flux surfaces are investigated, and the efficient reduction of saturated island widths through time modulation and spatial localization of the ECCD is explored. [1] Sovinec et al., JCP 195, 355 (2004) [2]www.compxco.com [3] Both the IPS development and the research presented here are part of the SWIM project. Funded by U.S. DoE.

Modeling of RF/MHD coupling using NIMROD, GENRAY, and the Integrated Plasma Simulator

NASA Astrophysics Data System (ADS)

Jenkins, Thomas; Schnack, D. D.; Sovinec, C. R.; Hegna, C. C.; Callen, J. D.; Ebrahimi, F.; Kruger, S. E.; Carlsson, J.; Held, E. D.; Ji, J.-Y.; Harvey, R. W.; Smirnov, A. P.

2009-05-01

We summarize ongoing theoretical/numerical work relevant to the development of a self--consistent framework for the inclusion of RF effects in fluid simulations; specifically considering resistive tearing mode stabilization in tokamak (DIII--D--like) geometry via ECCD. Relatively simple (though non--self--consistent) models for the RF--induced currents are incorporated into the fluid equations, markedly reducing the width of the nonlinearly saturated magnetic islands generated by tearing modes. We report our progress toward the self--consistent modeling of these RF--induced currents. The initial interfacing of the NIMROD* code with the GENRAY/CQL3D** codes (calculating RF propagation and energy/momentum deposition) via the Integrated Plasma Simulator (IPS) framework*** is explained, equilibration of RF--induced currents over the plasma flux surfaces is investigated, and studies exploring the efficient reduction of saturated island widths through time modulation and spatial localization of the ECCD are presented. *[Sovinec et al., JCP 195, 355 (2004)] **[www.compxco.com] ***[This research and the IPS development are both part of the SWIM project. Funded by U.S. DoE.

Real-time services in IP network architectures

NASA Astrophysics Data System (ADS)

Gilardi, Antonella

1996-12-01

The worldwide internet system seems to be the success key for the provision of real time multimedia services to both residential and business users and someone says that in such a way broadband networks will have a reason to exist. This new class of applications that use multiple media (voice, video and data) impose constraints to the global network nowadays consisting of subnets with various data links. The attention will be focused on the interconnection of IP non ATM and ATM networks. IETF and ATM forum are currently involved in the developing specifications suited to adapt the connectionless IP protocol to the connection oriented ATM protocol. First of all the link between the ATM and the IP service model has to be set in order to match the QoS and traffic requirements defined in the relative environment. A further significant topic is represented by the mapping of IP resource reservation model onto the ATM signalling and in the end it is necessary to define how the routing works when there are QoS parameters associated. This paper, considering only unicast applications, will examine the above issues taking as a starting point the situation where an host launches as call set up request with the relevant QoS and traffic descriptor and at some point a router at the edge of the ATM network has to decide how forwarding and request in order to establish an end to end link with the right capabilities. The aim is to compare the proposals emerging from different standard bodies to point out convergency or incompatibility.

Overview of Non-Solenoidal Startup Studies in the Pegasus ST

NASA Astrophysics Data System (ADS)

Bongard, M. W.; Barr, J. L.; Bodner, G. M.; Burke, M. G.; Fonck, R. J.; Pachicano, J. L.; Perry, J. M.; Reusch, J. A.; Richner, N. J.; Rodriguez Sanchez, C.; Schlossberg, D. J.

2016-10-01

Local helicity injection (LHI) is a non-solenoidal startup method pursued on Pegasus utilizing compact, high power current sources (Ainj 2 - 4 cm2, Iinj 10 kA, Vinj 1 kV) at the plasma edge. Outboard injectors (Ninj = 4 , Ainj = 8 cm2) produce Ip 170 kA plasmas compatible with Ohmic drive. A 0-D model that treats the plasma as a resistive element with time-varying inductance and enforces Ip limits from Taylor relaxation is used to interpret experimental Ip(t) in several scenarios. Strong inductive drive arises from the plasma shape evolution, in addition to poloidal field induction. A new injector system has recently been installed in the lower divertor region (Ninj = 2 , Ainj = 8 cm2) to explore the implications of geometric placement of the helicity injectors on LHI startup. This geometry supports tests of reconnection dynamics seen in NIMROD simulations, high-BT effects expected in larger devices, and LHI electron confinement with and without inductive assist. Plasmas with Ip > 130 kA, Vinj 0.5 kV, Δtpulse 8 ms and BT /BT , max <= 50 % are produced with the inboard system to date, consistent with performance expectations. Higher Ip is expected with increased BT, Vinj, and Δtpulse . Thomson scattering data in both geometries indicate high Te >= 100 eV during LHI, suggesting the confinement is not strongly stochastic. Conceptual design work is exploring the feasibility of coaxial helicity injection and ECH heating on Pegasus in addition to LHI. Work supported by US DOE Grant DE-FG02-96ER54375.

Human cord blood applications in cell therapy: looking back and look ahead.

PubMed

Zhou, Hongyan; Chang, Stephen; Rao, Mahendra

2012-08-01

Human umbilical cord blood (UCB) has been used as a reliable source of stem cells for blood-borne diseases and disorders. Recent advances in cell reprogramming technology to produce induced pluripotent stem (iPS) cells, which can be differentiated to multiple adult cell types, has further expanded the potential of cord blood cell therapy for treatment of non-blood-borne diseases. However, in order to harness this breakthrough technology and to provide clinical-grade cells for the patient, standardization of iPS production and differentiation, and good manufacturing practice (GMP) need to be employed. UCB is an ethical source of stem cells and has been used to treat diseases including leukemia, cancer and blood disorders. The development of iPS cell technology could potentially greatly increase the application of cord blood cells as a treatment for a broader range of diseases, UCB-iPS banks could, therefore, be a valuable complementary source of clinical-grade cells for cell therapy. The current applicability of GMP to UCB and UCB-iPS cell-based cell therapy will be discussed. Although cord blood stem cell therapies have been practiced for decades, UCB-iPS cell therapies are a new innovation currently in development. Successful clinical applications of such novel cell therapies will depend on the production of GMP-compliant cells and the establishment of cell banks.

Electronegative LDL-mediated cardiac electrical remodeling in a rat model of chronic kidney disease

PubMed Central

Lee, An-Sheng; Chen, Wei-Yu; Chan, Hua-Chen; Chung, Ching-Hu; Peng, Hsien-Yu; Chang, Chia-Ming; Su, Ming-Jai; Chen, Chu-Huang; Chang, Kuan-Cheng

2017-01-01

The mechanisms underlying chronic kidney disease (CKD)–associated higher risks for life-threatening ventricular tachyarrhythmias remain poorly understood. In rats subjected to unilateral nephrectomy (UNx), we examined cardiac electrophysiological remodeling and relevant mechanisms predisposing to ventricular arrhythmias. Adult male Sprague-Dawley rats underwent UNx (n = 6) or sham (n = 6) operations. Eight weeks later, the UNx group had higher serum blood urea nitrogen and creatinine levels and a longer electrocardiographic QTc interval than did the sham group. Patch-clamp studies revealed epicardial (EPI)-predominant prolongation of the action potential duration (APD) at 50% and 90% repolarization in UNx EPI cardiomyocytes compared to sham EPI cardiomyocytes. A significant reduction of the transient outward potassium current (Ito) in EPI but not in endocardial (ENDO) cardiomyocytes of UNx rats led to a decreased transmural gradient of Ito. The reduction of Ito currents in UNx EPI cardiomyocytes was secondary to downregulation of KChIP2 but not Kv4.2, Kv4.3, and Kv1.4 protein expression. Incubation of plasma electronegative low-density lipoprotein (LDL) from UNx rats with normal EPI and ENDO cardiomyocytes recapitulated the electrophysiological phenotype of UNx rats. In conclusion, CKD disrupts the physiological transmural gradient of Ito via downregulation of KChIP2 proteins in the EPI region, which may promote susceptibility to ventricular tachyarrhythmias. Electronegative LDL may underlie downregulation of KChIP2 in CKD. PMID:28094801

Investigations of a Cretaceous limestone with spectral induced polarization and scanning electron microscopy

NASA Astrophysics Data System (ADS)

Johansson, Sara; Sparrenbom, Charlotte; Fiandaca, Gianluca; Lindskog, Anders; Olsson, Per-Ivar; Dahlin, Torleif; Rosqvist, Håkan

2017-02-01

Characterization of varying bedrock properties is a common need in various contexts, ranging from large infrastructure pre-investigations to environmental protection. A direct current resistivity and time domain induced polarization (IP) survey aiming to characterize properties of a Cretaceous limestone was carried out in the Kristianstad basin, Sweden. The time domain IP data was processed with a recently developed method in order to suppress noise from the challenging urban setting in the survey area. The processing also enabled extraction of early decay times resulting in broader spectra of the time decays and inversion for Cole-Cole parameters. The aims of this study is to investigate if large-scale geoelectrical variations as well as small-scale structural and compositional variations exist within the Kristianstad limestone, and to evaluate the usefulness of Cole-Cole inverted IP data in early time ranges for bedrock characterization. The inverted sections showed variations within the limestone that could be caused by variations in texture and composition. Samples from a deep drilling in the Kristianstad basin were investigated with scanning electron microscopy and energy dispersive X-ray spectroscopy, and the results showed that varying amounts of pyrite, glauconite and clay matrix were present at different levels in the limestone. The local high IP anomalies in the limestone could be caused by these minerals otherwise the IP responses were generally weak. There were also differences in the texture of the limestone at different levels, governed by fossil shapes and composition, proportions of calcareous cement and matrix as well as amount of silicate grains. Textural variations may have implications on the variation in Cole-Cole relaxation time and frequency factor. However, more research is needed in order to directly connect microgeometrical properties in limestone to spectral IP responses. The results from this study show that it is possible to recover useable spectral information from early decay times. We also show that under certain conditions (e.g. relatively short relaxation times in the subsurface), it is possible to extract spectral information from time domain IP data measured with on-off times as short as 1 s.

Resonant tunneling with high peak to valley current ratio in SiO{sub 2}/nc-Si/SiO{sub 2} multi-layers at room temperature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, D. Y., E-mail: cdy7659@126.com; Nanjing University of posts and Telecommunications, Nanjing 210046; Sun, Y.

We have investigated carrier transport in SiO{sub 2}/nc-Si/SiO{sub 2} multi-layers by room temperature current-voltage measurements. Resonant tunneling signatures accompanied by current peaks are observed. Carrier transport in the multi-layers were analyzed by plots of ln(I/V{sup 2}) as a function of 1/V and ln(I) as a function of V{sup 1/2}. Results suggest that besides films quality, nc-Si and barrier sub-layer thicknesses are important parameters that restrict carrier transport. When thicknesses are both small, direct tunneling dominates carrier transport, resonant tunneling occurs only at certain voltages and multi-resonant tunneling related current peaks can be observed but with peak to valley current ratiomore » (PVCR) values smaller than 1.5. When barrier thickness is increased, trap-related and even high field related tunneling is excited, causing that multi-current peaks cannot be observed clearly, only one current peak with higher PVCR value of 7.7 can be observed. While if the thickness of nc-Si is large enough, quantum confinement is not so strong, a broad current peak with PVCR value as high as 60 can be measured, which may be due to small energy difference between the splitting energy levels in the quantum dots of nc-Si. Size distribution in a wide range may cause un-controllability of the peak voltages.« less

Application of high-performance liquid chromatography to the determination of glyoxylate synthesis in chick embryo liver.

PubMed

Qureshi, A A; Elson, C E; Lebeck, L A

1982-11-19

The isolation and identification of three major alpha-keto end products (glyoxylate, pyruvate, alpha-ketoglutarate) of the isocitrate lyase reaction in 18-day chick embryo liver have been described. This was accomplished by the separation of these alpha-keto acids as their 2,4-dinitrophenylhydrazones (DNPHs) by high-performance liquid chromatography (HPLC). The DNPHs of alpha-keto acids were eluted with an isocratic solvent system of methanol-water-acetic acid (60:38.5:1.5) containing 5 mM tetrabutylammonium phosphate from a reversed-phase ultrasphere C18 (IP) and from a radial compression C18 column. The separation can be completed on the radial compression column within 15-20 min as compared to 30-40 min with a conventional reversed-phase column. Retention times and peak areas were integrated for both the assay samples and reference compounds. A relative measure of alpha-keto acid in the peak was calculated by comparison with the standard. The identification of each peak was done on the basis of retention time matching, co-chromatography with authentic compounds, and stopped flow UV-VIS scanning between 240 and 440 nm. Glyoxylate represented 5% of the total product of the isocitrate lyase reaction. Day 18 parallels the peak period of embryonic hepatic glycogenesis which occurs at a time when the original egg glucose reserve has been depleted.

Inositol Hexakisphosphate Kinase-3 Regulates the Morphology and Synapse Formation of Cerebellar Purkinje Cells via Spectrin/Adducin

PubMed Central

Fu, Chenglai; Xu, Jing; Li, Ruo-Jing; Crawford, Joshua A.; Khan, A. Basit; Ma, Ting Martin; Cha, Jiyoung Y.; Snowman, Adele M.; Pletnikov, Mikhail V.

2015-01-01

The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells. SIGNIFICANCE STATEMENT We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function. PMID:26245967

26 CFR 1.1272-1 - Current inclusion of OID in income.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the amount of OID pursuant to the following formula: OIDshort = IP×(i/k)×f In which: OIDshort = The amount of OID allocable to the initial short accrual period IP = The issue price of the debt instrument i...

26 CFR 1.1272-1 - Current inclusion of OID in income.

Code of Federal Regulations, 2010 CFR

2010-04-01

... following formula: OIDshort = IP×(i/k)×f In which: OIDshort = The amount of OID allocable to the initial short accrual period IP = The issue price of the debt instrument i = The yield to maturity expressed as...

Role of Ipsdienol, Ipsenol, and cis-Verbenol in chemical ecology of Ips avulsus, Ips calligraphus, and Ips grandicollis (Coleoptera: Curculionidae: Scolytinae)

Treesearch

Jeremy D. Allison; Jessica I. McKenney; Daniel R. Miller; Matthew L. Gimmel

2012-01-01

ABSTRACT Stressed or damaged pine (Pinus sp.) trees in the southeastern United States are often colonized simultaneously by three southern Ips species (Coleoptera: Curculionidae: Scolytinae): small southern pine engraver, Ips avulsus (Eichhoff); sixspined ips, Ips calligraphus (Germar); and...

Comparison of gating dynamics of different IP3R channels with immune algorithm searching for channel parameter distributions

NASA Astrophysics Data System (ADS)

Cai, Xiuhong; Li, Xiang; Qi, Hong; Wei, Fang; Chen, Jianyong; Shuai, Jianwei

2016-10-01

The gating properties of the inositol 1, 4, 5-trisphosphate (IP3) receptor (IP3R) are determined by the binding and unbinding capability of Ca2+ ions and IP3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP3R (Oo-IP3R1), type-3 IP3R (Oo-IP3R3) and Spodoptera frugiperda IP3R (Sf-IP3R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP3Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model. By comparing the fitting parameter distributions of three IP3Rs, we suggest that the three types of IP3Rs have the similar open sensitivity in responding to IP3. The Oo-IP3R3 channel is easy to open in responding to low Ca2+ concentration, while Sf-IP3R channel is easily inhibited in responding to high Ca2+ concentration. We also show that the IP3 binding rate is not a sensitive parameter for stationary gating dynamics for three IP3Rs, but the inhibitory Ca2+ binding/unbinding rates are sensitive parameters for gating dynamics for both Oo-IP3R1 and Oo-IP3R3 channels. Such differences may be important in generating the spatially and temporally complex Ca2+ oscillations in cells. Our study also demonstrates that the immune algorithm can be applied for model parameter searching in biological systems.

Electromagnetic pulse-induced current measurement device

NASA Astrophysics Data System (ADS)

Gandhi, Om P.; Chen, Jin Y.

1991-08-01

To develop safety guidelines for exposure to high fields associated with an electromagnetic pulse (EMP), it is necessary to devise techniques that would measure the peak current induced in the human body. The main focus of this project was to design, fabricate, and test a portable, self-contained stand-on device that would measure and hold the peak current and the integrated change Q. The design specifications of the EMP-Induced Current Measurement Device are as follows: rise time of the current pulse, 5 ns; peak current, 20-600 A; charge Q, 0-20 microcoulombs. The device uses a stand-on parallel-plate bilayer sensor and fast high-frequency circuit that are well-shielded against spurious responses to high incident fields. Since the polarity of the incident peak electric field of the EMP may be either positive or negative, the induced peak current can also be positive or negative. Therefore, the device is designed to respond to either of these polarities and measure and hold both the peak current and the integrated charge which are simultaneously displayed on two separate 3-1/2 digit displays. The prototype device has been preliminarily tested with the EMP's generated at the Air Force Weapons Laboratory (ALECS facility) at Kirtland AFB, New Mexico.

Resilient Diffusive Clouds

DTIC Science & Technology

2017-02-01

scale blade servers (Dell PowerEdge) [20]. It must be recognized however, that the findings are distributed over this collection of architectures not...current operating system designs run into millions of lines of code. Moreover, they compound the opportunity for compromise by granting device drivers...properties (e.g. IP & MAC address) so as to invalidate an adversary’s surveillance data. The current running and bootstrapping instances of the micro

Disentangling the Origin and Heating Mechanism of Supernova Dust: Late-Time Spitzer Spectroscopy of the Type IIn SN 2005ip

NASA Technical Reports Server (NTRS)

Fox, Ori D.; Chevalier, Roger A.; Dwek, Eli; Skrutskie, Michael F.; Sugerman, Ben E. K.; Leisenring, Jarron M.

2010-01-01

This paper presents late-time near-infrared and Spitzer mid-infrared photometric and spectroscopic observations of warm dust in the Type IIn SN 2005ip in NGC 2906. The spectra show evidence for two dust components with different temperatures. Spanning the peak of the thermal emission, these observations provide strong constraints on the dust mass, temperature, and luminosity, which serve as critical diagnostics for disentangling the origin and heating mechanism of each component. The results suggest the warmer dust has a mass of approx. 5 x 10(exp -4) Solar Mass and originates from newly formed dust in the ejecta, continuously heated by the circumstellar interaction. By contrast, the cooler component likely originates from a circumstellar shock echo that forms from the heating of a large, pre-existing dust shell approx. 0.01 - 0.05 Solar Mass by the late-time circumstellar interaction. The progenitor wind velocity derived from the blue edge of the He I 1.083 micro P Cygni profile indicates a progenitor eruption likely formed this dust shell approx.100 years prior to the supernova explosion, which is consistent with a Luminous Blue Variable (LBV) progenitor star. Subject

Field Tolerances for the Triplet Quadrupoles of the LHC High Luminosity Lattice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nosochkov, Yuri; Cai, Y.; Jiao, Y.

2012-06-25

It has been proposed to implement the so-called Achromatic Telescopic Squeezing (ATS) scheme in the LHC high luminosity (HL) lattice to reduce beta functions at the Interaction Points (IP) up to a factor of 8. As a result, the nominal 4.5 km peak beta functions reached in the Inner Triplets (IT) at collision will be increased by the same factor. This, therefore, justifies the installation of new, larger aperture, superconducting IT quadrupoles. The higher beta functions will enhance the effects of the triplet quadrupole field errors leading to smaller beam dynamic aperture (DA). To maintain the acceptable DA, the effectsmore » of the triplet field errors must be re-evaluated, thus specifying new tolerances. Such a study has been performed for the so-called '4444' collision option of the HL-LHC layout version SLHCV3.01, where the IP beta functions are reduced by a factor of 4 in both planes with respect to a pre-squeezed value of 60 cm at two collision points. The dynamic aperture calculations were performed using SixTrack. The impact on the triplet field quality is presented.« less

Optical monitoring of ion beam Y-Ba-Cu-O sputtering

NASA Astrophysics Data System (ADS)

Klein, J. D.; Yen, A.

1990-11-01

The emission spectra resulting from ion beam sputtering a Y-Ba-Cu-O target were observed as a function of beam voltage and beam current. The spectra were relatively clean with several peaks readily attributed to each of Y, Ba, and Ar. Monitoring of copper and oxygen was more difficult with a single CuO peak and one O peak evident. The intensities of the cation peaks were linear with respect to beam voltage above 400 V. Since target current was found not to be directly proportional to beam current, target power was defined as the product of beam voltage and target current. The response of cation peak height to changes in target power was linear and similar for variations of either beam voltage or target current.

Evaluation of mechanical and optical behavior of current esthetic dental restorative CAD/CAM composites.

PubMed

Stawarczyk, Bogna; Liebermann, Anja; Eichberger, Marlis; Güth, Jan-Frederik

2015-03-01

To determine the mechanical and optical properties of CAD/CAM composites (LAVA Ultimate, Cerasmart, Shofu Block and two exp. CAD/CAM composites), a hybrid material (VITA Enamic), a leucite (IPS Empress CAD) and a lithium disilicate glass-ceramic (IPS e.max CAD). Three-point flexural strength (FS) was investigated according ISO 6872:2008 (N=240/n=30). Two-body wear (TBW) was analyzed in a chewing simulator (1,200,000 cycles, 50N, 5°/55°C) using human teeth as antagonists (N=120/n=15). Quantitative analysis of wear was carried out with a 3D-scanner and associated matching software. Discoloration rate (DR) after 14 days of storage in cress, curry, red wine, and distilled water (N=384/n=12), and translucency (T) (N=384/n=48) of CAD/CAM materials were measured in a spectrophotometer (400-700nm wavelength). Data were analyzed using two-/one-way ANOVA with Scheffé post-hoc test, Kruskal-Wallis-H test, and linear mixed models (α=0.05). IPS e.max CAD showed the highest FS (p<0.001), followed by LAVA Ultimate; however, not different from the remaining CAD/CAM composites (exception: Shofu Block). The lowest FS showed VITA Enamic and IPS Empress CAD (p<0.001). IPS Empress CAD, VITA Enamic, exp. CAD/CAM composite 2, followed by IPS e.max presented lower material TBW than the remaining CAD/CAM materials (p<0.001). The highest antagonist wear was observed for the tested glass-ceramics and the hybrid material (p<0.001). Storage medium (red wine>curry>cress>distilled water) exerted the highest influence on DR (p<0.001), closely followed by CAD/CAM material. Glass-ceramics showed lower DR than CAD/CAM composites (p<0.001). CAD/CAM composites presented moderate FS, high T and antagonist friendly behavior. Glass-ceramic demonstrated the most favorable DR and lowest TBW on the material side. Copyright © 2015 Elsevier Ltd. All rights reserved.

Scoping review of resources for integrating evidence-based supported employment into spinal cord injury rehabilitation.

PubMed

Cotner, Bridget A; Ottomanelli, Lisa; Keleher, Virginia; Dirk, Lynn

2018-02-27

Individual placement and support (IPS), an evidence-based supported employment (SE) program, has helped Veterans with spinal cord injury (SCI) receiving care in the Veterans Health Administration to obtain work. To facilitate integration of IPS into SCI rehabilitation, resources are needed. A scoping review was conducted to identify tools and resources suitable for providers of SCI care. Applying a modified version of Arksey and O'Malley's framework, a scoping review of literature on SE tools or resources was conducted. The original review focused on resources published between 2002 and 2015 and available in English. Prior to publication an updated review through 2017 was conducted. From 1822 tools and resources identified in the initial review, 24 met criteria for inclusion and were evaluated by an advisory panel of experts, who selected 16 tools that addressed five topics: IPS in SCI (n = 2) orientation to SCI (n = 3); IPS SE (n = 7), job accommodations (n = 2), and benefits planning (n = 2). The updated review yielded no tools or resources that met inclusion criteria. Despite few resources to guide implementation of IPS in SCI, 16 essential resources were identified that, combined into a toolkit, may facilitate translation of IPS in SCI from research to clinical care. Implications for rehabilitation The toolkit consists of 16 essential resources and is currently available online to all persons involved in spinal cord injury rehabilitation to educate them about this effective means of assisting persons with spinal cord injury to find employment and to facilitate translation of individual placement and support in spinal cord injury from research to clinical care. While expert-informed, the toolkit is being field tested with both clinical and vocational providers to facilitate the adoption of individual placement and support by spinal cord injury rehabilitation programs. The revised version will be made available online.

Comparison of Post-Processing Techniques for the Detection of Perfusion Defects by Cardiac Computed Tomography in Patients Presenting with Acute ST Segment Elevation Myocardial Infarction

PubMed Central

Rogers, Ian S.; Cury, Ricardo C.; Blankstein, Ron; Shapiro, Michael D.; Nieman, Koen; Hoffmann, Udo; Brady, Thomas J.; Abbara, Suhny

2010-01-01

Background Despite rapid advances in cardiac computed tomography (CT), a strategy for optimal visualization of perfusion abnormalities on CT has yet to be validated. Objective To evaluate the performance of several post-processing techniques of source data sets to detect and characterize perfusion defects in acute myocardial infarctions with cardiac CT. Methods Twenty-one subjects (18 men; 60 ± 13 years) that were successfully treated with percutaneous coronary intervention for ST-segment myocardial infarction underwent 64-slice cardiac CT and 1.5 Tesla cardiac MRI scans following revascularization. Delayed enhancement MRI images were analyzed to identify the location of infarcted myocardium. Contiguous short axis images of the left ventricular myocardium were created from the CT source images using 0.75mm multiplanar reconstruction (MPR), 5mm MPR, 5mm maximal intensity projection (MIP), and 5mm minimum intensity projection (MinIP) techniques. Segments already confirmed to contain infarction by MRI were then evaluated qualitatively and quantitatively with CT. Results Overall, 143 myocardial segments were analyzed. On qualitative analysis, the MinIP and thick MPR techniques had greater visibility and definition than the thin MPR and MIP techniques (p < 0.001). On quantitative analysis, the absolute difference in Hounsfield Unit (HU) attenuation between normal and infarcted segments was significantly greater for the MinIP (65.4 HU) and thin MPR (61.2 HU) techniques. However, the relative difference in HU attenuation was significantly greatest for the MinIP technique alone (95%, p < 0.001). Contrast to noise was greatest for the MinIP (4.2) and thick MPR (4.1) techniques (p < 0.001). Conclusion The results of our current investigation found that MinIP and thick MPR detected infarcted myocardium with greater visibility and definition than MIP and thin MPR. PMID:20579617

Fluorescence Fluctuations and Equivalence Classes of Ca 2+ Imaging Experiments

PubMed Central

Piegari, Estefanía; Lopez, Lucía; Perez Ipiña, Emiliano; Ponce Dawson, Silvina

2014-01-01

release into the cytosol through inositol 1,4,5-trisphosphate receptors (IP3Rs) plays a relevant role in numerous physiological processes. IP3R-mediated signals involve -induced -release (CICR) whereby release through one open IP3R induces the opening of other channels. IP3Rs are apparently organized in clusters. The signals can remain localized (i.e., puffs) if CICR is limited to one cluster or become waves that propagate between clusters. puffs are the building blocks of waves. Thus, there is great interest in determining puff properties, especially in view of the current controversy on the spatial distribution of activatable IP3Rs. puffs have been observed in intact cells with optical techniques proving that they are intrinsically stochastic. Obtaining a correct picture of their dynamics then entails being able to detect the whole range of puff sizes. puffs are observed using visible single-wavelength dyes, slow exogenous buffers (e.g., EGTA) to disrupt inter-cluster CICR and UV-photolyzable caged IP3. Single-wavelength dyes increase their fluorescence upon calcium binding producing images that are strongly dependent on their kinetic, transport and photophysical properties. Determining the artifacts that the imaging setting introduces is particularly relevant when trying to analyze the smallest signals. In this paper we introduce a method to estimate the expected signal-to-noise ratio of imaging experiments that use single-wavelength dyes. The method is based on the Number and Brightness technique. It involves the performance of a series of experiments and their subsequent analysis in terms of a fluorescence fluctuation model with which the model parameters are quantified. Using the model, the expected signal-to-noise ratio is then computed. Equivalence classes between different experimental conditions that produce images with similar signal-to-noise ratios can then be established. The method may also be used to estimate the smallest signals that can reliably be observed with each setting. PMID:24776736

Using NetMeeting for remote configuration of the Otto Bock C-Leg: technical considerations.

PubMed

Lemaire, E D; Fawcett, J A

2002-08-01

Telehealth has the potential to be a valuable tool for technical and clinical support of computer controlled prosthetic devices. This pilot study examined the use of Internet-based, desktop video conferencing for remote configuration of the Otto Bock C-Leg. Laboratory tests involved connecting two computers running Microsoft NetMeeting over a local area network (IP protocol). Over 56 Kbs(-1), DSL/Cable, and 10 Mbs(-1) LAN speeds, a prosthetist remotely configured a user's C-Leg by using Application Sharing, Live Video, and Live Audio. A similar test between sites in Ottawa and Toronto, Canada was limited by the notebook computer's 28 Kbs(-1) modem. At the 28 Kbs(-1) Internet-connection speed, NetMeeting's application sharing feature was not able to update the remote Sliders window fast enough to display peak toe loads and peak knee angles. These results support the use of NetMeeting as an accessible and cost-effective tool for remote C-Leg configuration, provided that sufficient Internet data transfer speed is available.

Advancing Non-Solenoidal Startup on the Pegasus ST

NASA Astrophysics Data System (ADS)

Reusch, J. A.; Barr, J. L.; Bodner, G. M.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Pachicano, J. L.; Perry, J. M.; Richner, N. J.; Rodriguez Sanchez, C.; Schlossberg, D. J.

2016-10-01

The Pegasus experiment utilizes compact, edge-localized current sources (Ainj 2 - 4 cm2, Iinj 10 kA, Vinj 1 kV) for non-solenoidal local helicity injection (LHI) startup. Recent campaigns are comparing two injector geometries that vary the differing relative contributions of DC helicity input and non-solenoidal inductive voltages. A predictive 0-D model that treats the plasma as a resistive element with time-varying inductance and enforces Ip limits from Taylor relaxation was tested with inward growth of the plasma current channel using injectors on the outboard midplane. Strong inductive drive arises from plasma shape evolution and poloidal field (PF) induction. A major unknown in the model is the resistive dissipation, and hence the electron confinement. Te (R) profile measurements in LHI show centrally-peaked Te > 100 eV while the plasma is coupled to the injectors, suggesting LHI confinement is not strongly stochastic. A second campaign utilizes new injectors in the lower divertor region. This geometry trades subtler relaxation field programming and reduced PF induction for higher HI rates. Present efforts are developing relaxation methods at high BT, with relaxation at BT , inj > 0.15 T achieved to date via higher Iinj and PF manipulation. Conceptual design studies of coaxial helicity injection (CHI) and ECH heating systems for Pegasus have been initiated to explore direct comparison of LHI to CHI with and without ECH assist. Supported by US DOE Grants DE-FG02-96ER54375, DE-SC0006928.

The first super geomagnetic storm of solar cycle 24: "The St. Patrick day (17 March 2015)" event

NASA Astrophysics Data System (ADS)

Wu, C. C.; Liou, K.; Socker, D. G.; Howard, R.; Jackson, B. V.; Yu, H. S.; Hutting, L.; Plunkett, S. P.

2015-12-01

The first super geomagnetic storm of solar cycle 24 occurred on the "St. Patrick's day" (17 March 2015). Notably, it was a two-step storm. The source of the storm can be traced back to the solar event on March 15, 2015. At ~2:10 UT on that day, SOHO/LASCO C3 recorded a partial halo corona mass ejection (CME) which was associated with a C9.1/1F flare (S22W25) and a series of type II/IV radio bursts. The propagation speed of this CME is estimated to be ~668 km/s during 02:10 - 06:20 UT (Figure 1). An interplanetary (IP) shock, likely driven by the CME, arrived at the Wind spacecraft at 03:59 UT on 17 March (Figure 2). The arrival of the IP shock at the Earth may have caused a sudden storm commencement (SSC) at 04:45 UT on March 17. The storm intensified (Dst dropped to -80 nT at ~10:00 UT) during the crossing of the CME sheath. Later, the storm recovered slightly (Dst ~ -50 nT) after the IMF turned northward. At 11:01 UT, IMF started turning southward again due to the large magnetic cloud (MC) field itself and caused the second storm intensification, reaching Dst = - 228 nT on March 18. We conclude that the St. Patrick day event is a two-step storm. The first step is associated with the sheath, whereas the second step is associated with the MC. Here, we employ a numerical simulation using the global, three-dimensional (3D), time-dependent, magnetohydrodynamic (MHD) model (H3DMHD, Wu et al. 2007) to study the CME propagation from the Sun to the Earth. The H3DMHD model has been modified so that it can be driven by (solar wind) data at the inner boundary of the computational domain. In this study, we use time varying, 3D solar wind velocity and density reconstructed from STELab, Japan interplanetary scintillation (IPS) data by the University of California, San Diego, and magnetic field at the IPS inner boundary provided by CSSS model closed-loop propagation (Jackson et a., 2015). The simulation result matches well with the in situ solar wind plasma and field data at Wind, in terms of the peak values of the IP shock and its arrival time (Figure 3). The simulation not only helps us to identify the driver of the IP shock, but also demonstrates that the modified H3DMHD model is capable of realistic simulations of large solar event. In this presentation, we will discuss the CME/storm event with detailed data from observations (Wind and SOHO) and our numerical simulation.

Cyber Infrastructure Protection

DTIC Science & Technology

2011-05-01

274 TOWARD A SOLUTION THAT WORKS Building on our long history of involvement in assuring all types of communications networks, Tel- cordia has...wireless, and security areas. He currently has responsibility for a new Tel- cordia software product in IP network management, and has led all product

A Review of Pedestrian Indoor Positioning Systems for Mass Market Applications

PubMed Central

Barcelo, Marc; Vicario, Jose Lopez

2017-01-01

In the last decade, the interest in Indoor Location Based Services (ILBS) has increased stimulating the development of Indoor Positioning Systems (IPS). In particular, ILBS look for positioning systems that can be applied anywhere in the world for millions of users, that is, there is a need for developing IPS for mass market applications. Those systems must provide accurate position estimations with minimum infrastructure cost and easy scalability to different environments. This survey overviews the current state of the art of IPSs and classifies them in terms of the infrastructure and methodology employed. Finally, each group is reviewed analysing its advantages and disadvantages and its applicability to mass market applications. PMID:28829386

Research into alternative network approaches for space operations

NASA Technical Reports Server (NTRS)

Kusmanoff, Antone L.; Barton, Timothy J.

1990-01-01

The main goal is to resolve the interoperability problem of applications employing DOD TCP/IP (Department of Defence Transmission Control Protocol/Internet Protocol) family of protocols on a CCITT/ISO based network. The objective is to allow them to communicate over the CCITT/ISO protocol GPLAN (General Purpose Local Area Network) network without modification to the user's application programs. There were two primary assumptions associated with the solution that was actually realized. The first is that the solution had to allow for future movement to the exclusive use of the CCITT/ISO standards. The second is that the solution had to be software transparent to the currently installed TCP/IP and CCITT/ISO user application programs.

Improved Confinement by Edge Multi-pulse Turbulent Heating on HT-6M Tokamak

NASA Astrophysics Data System (ADS)

Mao, Jian-shan; Luo, Jia-rong; Li, Jian-gang; Pan, Yuan; Wang, Mao-quan; Liu, Bao-hua; Wan, Yuan-xi; Li, Qiang; Wu, Xin-chao; Liang, Yun-feng; Xu, Yu-hong; Yu, Chang-xuan

1997-10-01

In the recent experiment on HT-6M tokamak, an improved ohmic confinement phase has been observed after application of the edge multi-pulse turbulent heating, and variance of plasma current ΔIp/Ip is about 14-20%. The improved edge plasma confinement phase is characterized by (a) increased average electron density bar Ne and electron temperature Te; (b) reduced Hα radiation from the edge; (c) steeper density and temperature profiles at the edge; (d) a more negative radial electric field over a region of ~ 5 mm deep inside the limiter; (e) a deeper electrostatic potential well at the edge; (f) reduced magnetic fluctuations at the edge.

An infrastructure with a unified control plane to integrate IP into optical metro networks to provide flexible and intelligent bandwidth on demand for cloud computing

NASA Astrophysics Data System (ADS)

Yang, Wei; Hall, Trevor

2012-12-01

The Internet is entering an era of cloud computing to provide more cost effective, eco-friendly and reliable services to consumer and business users and the nature of the Internet traffic will undertake a fundamental transformation. Consequently, the current Internet will no longer suffice for serving cloud traffic in metro areas. This work proposes an infrastructure with a unified control plane that integrates simple packet aggregation technology with optical express through the interoperation between IP routers and electrical traffic controllers in optical metro networks. The proposed infrastructure provides flexible, intelligent, and eco-friendly bandwidth on demand for cloud computing in metro areas.

Past, present, and future of endobronchial laser photoresection

PubMed Central

Khemasuwan, Danai; Wang, Ko-Pen

2015-01-01

Laser photoresection of central airway obstruction is a useful tool for an Interventional Pulmonologist (IP). Endobronchial therapy of the malignant airway obstruction is considered as a palliative measure or a bridge therapy to the definite treatment of cancer. Several ablative therapies such as electrocautery, argon plasma coagulation (APC), cryotherapy and laser photoresection exist in the armamentarium of IP to tackle such presentations. Besides Neodymium-Yttrium, Aluminum, Garnet (Nd:YAG) laser, there are several different types of laser that have been used by the pulmonologist with different coagulative and cutting properties. This chapter focuses on the historical perspective, current status, and potentials of lasers in the management of central airway lesions. PMID:26807285

Parametric Optimization of Wire Electrical Discharge Machining of Powder Metallurgical Cold Worked Tool Steel using Taguchi Method

NASA Astrophysics Data System (ADS)

Sudhakara, Dara; Prasanthi, Guvvala

2017-04-01

Wire Cut EDM is an unconventional machining process used to build components of complex shape. The current work mainly deals with optimization of surface roughness while machining P/M CW TOOL STEEL by Wire cut EDM using Taguchi method. The process parameters of the Wire Cut EDM is ON, OFF, IP, SV, WT, and WP. L27 OA is used for to design of the experiments for conducting experimentation. In order to find out the effecting parameters on the surface roughness, ANOVA analysis is engaged. The optimum levels for getting minimum surface roughness is ON = 108 µs, OFF = 63 µs, IP = 11 A, SV = 68 V and WT = 8 g.

ChIP and ChIP-Related Techniques: Expanding the Fields of Application and Improving ChIP Performance.

PubMed

Visa, Neus; Jordán-Pla, Antonio

2018-01-01

Protein-DNA interactions in vivo can be detected and quantified by chromatin immunoprecipitation (ChIP). ChIP has been instrumental for the advancement of epigenetics and has set the groundwork for the development of a number of ChIP-related techniques that have provided valuable information about the organization and function of genomes. Here, we provide an introduction to ChIP and discuss the applications of ChIP in different research areas. We also review some of the strategies that have been devised to improve ChIP performance.

The prevalence of human papillomavirus infection in Iranian patients with sinonasal inverted papilloma.

PubMed

Jalilvand, Somayeh; Saidi, Masoumeh; Shoja, Zabihollah; Ghavami, Nastaran; Hamkar, Rasool

2016-03-01

Inverted papilloma (IP) is an uncommon disease which arises in the mucosal membrane of the nasal cavity and paranasal sinus. It has been proposed that human papillomavirus (HPV) is the causal agent in the pathogenesis of IP and plays a key role in the progression from benign IP to malignancy. As there are no prior studies that focus on an Iranian population, this study intended to characterize the prevalence of HPV types in benign and malignant forms of IP. In this retrospective study, we included a total of 40 IP patients [37 benign IP and 3 IP/squamous cell carcinoma (SCC)] who were referred to Amiralam Hospital in Tehran from 2004-2006. HPV was detected in 18.9% and 100% of IP and IP/SCC cases, respectively. In all HPV positive cases of IP and IP/SCC cases, HPV6/11 and HPV16/18 were detected, respectively. Therefore, HPV types were different between the IP and IP/SCC patients, and this difference was statistically significant (p = 0.002). This study suggests that HPV6 and 11 may be involved in the development of IP, but HPV16 and 18 likely play an important role in the progression from benign to malignant form of IP. Copyright © 2015. Published by Elsevier Taiwan LLC.

Silicon-Based Quantum MOS Technology Development

DTIC Science & Technology

2000-03-07

resonant interband tunnel diodes were demonstrated with peak current density greater than 104 A/cm2; peak-to-valley current ratio exceeding 2 was...photon emission reduce the peak-to-valley current ratio and device performance. Therefore, interband tunnel devices should be more resilient to...Comparison of bipolar interband tunnel and optical devices: (a) Esaki diode biased into the valley current region and (b) optical light emitter. The Esaki

Anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) leaf extract in mice.

PubMed

Amabeoku, G J; Green, I; Kabatende, J

2007-05-30

The anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) was investigated by studying the effects of both aqueous and methanol extracts of the plant species on seizures induced by pentylenetetrazole, bicuculline, picrotoxin and N-methyl-dl-aspartic in mice. Aqueous extract of Cotyledon orbiculata (50-400mg/kg, i.p.) and methanol extract (100-400mg/kg, i.p.) significantly prolonged the onset of tonic seizures induced by pentylenetetrazole (95mg/kg, i.p.). Methanol extract (400mg/kg, i.p.) also significantly reduced the incidence of the seizures. One hundred to two hundred milligrams/kilogram (i.p.) of aqueous extract of Cotyledon orbiculata significantly delayed the onset of the tonic seizures induced by bicuculline (40mg/kg, i.p.), picrotoxin (12mg/kg, i.p.) and N-methyl-dl-aspartic acid (NMDLA, 400mg/kg, i.p.). Similarly, methanol extract (100-400mg/kg, i.p.) significantly delayed the onset of the tonic seizures induced by bicuculline (40mg/kg, i.p.) and picrotoxin (12mg/kg, i.p.) while 100mg/kg (i.p.) significantly delayed the onset of N-methyl-dl-aspartic acid (NMDLA, 400mg/kg, i.p.)-induced seizures. Methanol extract (200mg/kg, i.p.) significantly reduced the incidence of the seizures induced by bicuculline (40mg/kg, i.p.). Phenobarbitone (12mg/kg, i.p.) and diazepam (0.5mg/kg, i.p.) effectively antagonized only seizures induced by PTZ (95mg/kg, i.p.), bicuculline (40mg/kg, i.p.) and picrotoxin (12mg/kg, i.p.). Phenytoin (30mg/kg, i.p.) did not affect any of the seizures to any significant extent. The data obtained suggest that both aqueous and methanol extracts of Cotyledon orbiculata have anticonvulsant property and may probably be affecting both gabaergic and glutaminergic mechanisms to exert its effect. The phytochemical analysis carried out revealed the presence of cardiac glycosides, saponins, tannins, reducing sugar and triterpene steroids in the plant extract.

Phorbol 12,13-dibutyrate and 1-oleyl-2-acetyldiacylglycerol stimulate inositol trisphosphate dephosphorylation in human platelets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molina y Vedia, L.M.; Lapetina, E.G.

1986-08-15

Inositol trisphosphate (IP3) is formed in response to specific agonists that cause activation of phospholipase C and degradation of phosphatidylinositol bisphosphate. IP3 is a second messenger that releases Ca/sup 2 +/ from the dense tubular system to the cytosol in stimulated platelets. Our present information indicates that (/sup 3/H)IP3 is dephosphorylated to (/sup 3/H)inositol bisphosphate (IP2) and (/sup 3/H)inositol monophosphate (IP) by human platelets treated with 0.05-0.10% Triton X-100. This dephosphorylation of (/sup 3/H)IP3 to (/sup 3/H)IP2 and (/sup 3/H)IP is also observed when platelets are permeabilized by electrical stimulation or by 20 micrograms/ml saponin. These detergents or electropermeabilization allowmore » IP3 to access cytosolic IP3 phosphatase. Pretreatment of intact platelets with phorbol dibutyrate and 1-oleyl-2-acetyldiacylglycerol for 30 s, at concentrations that maximally activate protein kinase C, stimulates the conversion of IP3 to IP2 and IP. This suggests a role for protein kinase C in the regulation of IP3 degradation.« less

IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X-ray crystallography.

PubMed

Hamada, Kozo; Miyatake, Hideyuki; Terauchi, Akiko; Mikoshiba, Katsuhiko

2017-05-02

The inositol 1,4,5-trisphosphate (IP 3 ) receptor (IP 3 R) is an IP 3 -gated ion channel that releases calcium ions (Ca 2+ ) from the endoplasmic reticulum. The IP 3 -binding sites in the large cytosolic domain are distant from the Ca 2+ conducting pore, and the allosteric mechanism of how IP 3 opens the Ca 2+ channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP 3 R in the absence and presence of IP 3 Analyses of two distinct space group crystals uncovered an IP 3 -dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and channel domains. Mutagenesis of the IP 3 R channel revealed an essential role of a leaflet structure in the α-helical domain. These results suggest that the curvature α-helical domain relays IP 3 -controlled global conformational dynamics to the channel through the leaflet, conferring long-range allosteric coupling from IP 3 binding to the Ca 2+ channel.

Briefer assessment of social network drinking: A test of the Important People Instrument-5 (IP-5).

PubMed

Hallgren, Kevin A; Barnett, Nancy P

2016-12-01

The Important People instrument (IP; Longabaugh et al., 2010) is one of the most commonly used measures of social network drinking. Although its reliability and validity are well-supported, the length of the instrument may limit its use in many settings. The present study evaluated whether a briefer, 5-person version of the IP (IP-5) adequately reproduces scores from the full IP. College freshmen (N = 1,053) reported their own past-month drinking, alcohol-related consequences, and information about drinking in their close social networks at baseline and 1 year later. From this we derived network members' drinking frequency, percentage of drinkers, and percentage of heavy drinkers, assessed for up to 10 (full IP) or 5 (IP-5) network members. We first modeled the expected concordance between full-IP scores and scores from simulated shorter IP instruments by sampling smaller subsets of network members from full IP data. Then, using quasi-experimental methods, we administered the full IP and IP-5 and compared the 2 instruments' score distributions and concurrent and year-lagged associations with participants' alcohol consumption and consequences. Most of the full-IP variance was reproduced from simulated shorter versions of the IP (ICCs ≥ 0.80). The full IP and IP-5 yielded similar score distributions, concurrent associations with drinking (r = 0.22 to 0.52), and year-lagged associations with drinking. The IP-5 retains most of the information about social network drinking from the full IP. The shorter instrument may be useful in clinical and research settings that require frequent measure administration, yielding greater temporal resolution for monitoring social network drinking. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Inositol 1,4,5-trisphosphate receptor regulates replication, differentiation, infectivity and virulence of the parasitic protist Trypanosoma cruzi.

PubMed

Hashimoto, Muneaki; Enomoto, Masahiro; Morales, Jorge; Kurebayashi, Nagomi; Sakurai, Takashi; Hashimoto, Tetsuo; Nara, Takeshi; Mikoshiba, Katsuhiko

2013-03-01

In animals, inositol 1,4,5-trisphosphate receptors (IP3 Rs) are ion channels that play a pivotal role in many biological processes by mediating Ca(2+) release from the endoplasmic reticulum. Here, we report the identification and characterization of a novel IP3 R in the parasitic protist, Trypanosoma cruzi, the pathogen responsible for Chagas disease. DT40 cells lacking endogenous IP3 R genes expressing T. cruzi IP3 R (TcIP3 R) exhibited IP3 -mediated Ca(2+) release from the ER, and demonstrated receptor binding to IP3 . TcIP3 R was expressed throughout the parasite life cycle but the expression level was much lower in bloodstream trypomastigotes than in intracellular amastigotes or epimastigotes. Disruption of two of the three TcIP3 R gene loci led to the death of the parasite, suggesting that IP3 R is essential for T. cruzi. Parasites expressing reduced or increased levels of TcIP3 R displayed defects in growth, transformation and infectivity, indicating that TcIP3 R is an important regulator of the parasite's life cycle. Furthermore, mice infected with T. cruzi expressing reduced levels of TcIP3 R exhibited a reduction of disease symptoms, indicating that TcIP3 R is an important virulence factor. Combined with the fact that the primary structure of TcIP3 R has low similarity to that of mammalian IP3 Rs, TcIP3 R is a promising drug target for Chagas disease. © 2013 Blackwell Publishing Ltd.

Thermal power and heat energy of cloud-to-ground lightning process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xuejuan; Yuan, Ping; Xue, Simin

2016-07-15

A cloud-to-ground lightning flash with nine return strokes has been recorded using a high speed slitless spectrograph and a system composed of a fast antenna and a slow antenna. Based on the spectral data and the synchronous electric field changes that were caused by the lightning, the electrical conductivity, the channel radii, the resistance per unit length, the peak current, the thermal power at the instant of peak current, and the heat energy per unit length during the first 5 μs in the discharge channel have all been calculated. The results indicate that the channel radii have linear relationships with themore » peak current. The thermal power at the peak current time increases with increasing resistance, but exponential decays with the square of the peak current.« less

The management of the acute ischemic priapism: A state of the art review.

PubMed

Falcone, M; Gillo, A; Capece, M; Raheem, A; Ralph, D; Garaffa, G

2017-12-01

To review the current literature on early penile prosthesis implantation in patients with refractory ischemic priapism (IP). A systematic search for the terms "penile prosthesis", "priapism", "impotence", "fibrosis", "downsized prosthesis cylinders", and "patient satisfaction" has been carried out in PubMed, EMBASE, Cochrane, SCOPUS and Science Citation Index databases. Cavernosal tissue damage in IP is time related. Conservative measures and aspiration with or without intracorporeal instillation of α-adrenergic agonists are usually successful in the early stages. Shunt surgery in patients remains debatable, as the lack of response to aspiration and instillation of α-adrenergic agonists indicates that irreversible changes in the cavernosal smooth muscle are likely to have already occurred. Immediate penile prosthesis implantation in patients with refractory IP settles the priapic episode, maintains the long term rigidity necessary to engage in penetrative sexual intercourse and prevents the otherwise inevitable penile shortening. Although complication rates after penile prosthesis implantation in acute priapism are higher than in virgin cases, they are still lower than after implantation in patients with severe corporal fibrosis due to chronic priapism. Regardless of the complication rates, penile prosthesis implantation in refractory IP should be preferred as it allows the preservation of penile length, which is one of the main factors influencing postoperative patient's satisfaction following surgery. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Amphetamine effects on dopamine levels and behavior following cannabinoid exposure during adolescence.

PubMed

Ellgren, Maria; Hurd, Yasmin L; Franck, Johan

2004-08-23

The cannabis gateway hypothesis purports that early exposure to cannabis is a risk factor for subsequent use of other addictive drugs, e.g., psychostimulants. Neurobiological sensitization, consistent with a gateway hypothesis, was currently studied in regard to amphetamine response. Rats were exposed to the cannabinoid receptor agonist WIN 55,212-2 [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone] 1.25 mg/kg, intraperitoneally; i.p. for 5 days during early adolescence. Amphetamine (0.5 mg/kg, i.p.) or WIN 55,212-2 (1.25 mg/kg, i.p.) was administered in late adolescence and in vivo dopamine levels were simultaneously measured in the nucleus accumbens. Locomotor and stereotyped behaviors were also monitored in rats pretreated with WIN 55,212-2 (0.625, 1.25 or 2.5 mg/kg) or Delta-9-tetrahydrocannabinol (0.75, 1.5 or 3.0 mg/kg, i.p.) for 5 days during early adolescence and challenged with amphetamine (0.5 or 2.0 mg/kg) in late adolescence or as adults. Pretreatment with WIN 55,212-2 or Delta-9-tetrahydrocannabinol during early adolescence did not alter the dopaminergic or behavioral responses to amphetamine in adolescence or adulthood. In conclusion, these findings do not support the cannabis gateway hypothesis in regard to subsequent amphetamine exposure.

Dependence of SOL widths on plasma parameters in NSTX

NASA Astrophysics Data System (ADS)

Ahn, Joon-Wook; Maingi, Rajesh; Boedo, Jose; Soukhanovskii, Vlad; Leblanc, Ben; Kaita, Robert

2008-11-01

The dependence of various upstream Scrape-Off Layer (SOL) widths on the line-averaged density (n e), plasma current (Ip), and power into the SOL (PSOL) for H-mode plasmas was investigated, using the mid-plane fast reciprocating probe and Thomson scattering diagnostics, in the National Spherical Torus Experiment (NSTX). The heat flux width (λq) at the divertor plate, measured by the IR camera, was also measured and compared with the upstream SOL widths. The edge density profile remains fixed during the H-mode, such that the separatrix density is constant even though n e is ramping. Thus λq, λTe, and λne are insensitive to n e. λTe and λjsat have strong negative dependence on Ip, whereas there was only a very weak change in λne when Ip was varied. These empirical results have been compared with scaling laws in the literature. The λTe dependence on Ip is consistent with an H-mode λTe scaling law, while the insensitivity of λne to n e is not consistent with the λne scaling law. Dependence of decay lengths on plasma parameters in a wide range of plasma conditions will be presented. This work was supported by the US Department of Energy, contract numbers DE-FG02-03ER54731, DE-AC02-76CH03073, DE-AC05-00OR22725, and DE-AC52-07NA27344.

Surface characterization of current composites after toothbrush abrasion.

PubMed

Takahashi, Rena; Jin, Jian; Nikaido, Toru; Tagami, Junji; Hickel, Reinhard; Kunzelmann, Karl-Heinz

2013-01-01

The present study was designed to evaluate the surface roughness and the gloss of current composites before and after toothbrush abrasion. We assessed forty dimensionally standardized composite specimens (n=8/group) from five composites: two nanohybrids (i. e., IPS Empress Direct Enamel and IPS Empress Direct Dentin), two microhybrids (i. e., Clearfil AP-X and Filtek Z250) and one organically modified ceramics (Admira). All of the specimens were polished with 4000-grid silicon carbide papers. Surface roughness was measured with a profilometer and gloss was measured with a glossmeter before and after powered toothbrush abrasion with a 1:1 slurry (dentifrice/tap water) at 12,000 strokes in a toothbrush simulator. There was a significant increase in the surface roughness and a reduction in gloss after toothbrush abrasion in all of the composites except Clearfil AP-X (p<0.05). Simple regression analysis showed that there was not an association between the surface roughness and the gloss (R(2)=0.191, p<0.001).

Transverse profile of the electron beam for the RHIC electron lenses

DOE PAGES

Gu, X.; Altinbas, Z.; Costanzo, M.; ...

2015-07-10

To compensate for the beam-beam effects from the proton-proton interactions at the two interaction points IP6 and IP8 in the Relativistic Heavy Ion Collider (RHIC), we are constructing two electron lenses (e-lenses) that we plan to install in the interaction region IR10. Before installing them, the electron gun, collector, instrumentation were tested and the electron beam properties were qualified on an electron lens test bench. We will present the test results and discuss our measurement of the electron beam current and of the electron gun perveance. We achieved a maximum current of 1 A with 5 kV energy for bothmore » the pulsed- and the DC-beam (which is a long turn-by-turn pulse beam). We measured beam transverse profiles with an Yttrium Aluminum Garnet (YAG) screen and pinhole detector, and compared those to simulated beam profiles. Measurements of the pulsed electron beam stability were obtained by measuring the modulator voltage.« less

Imaging Coronal Mass Ejections and Large-Scale Solar Wind Structure Using IPS and Thomson-Scattered Sunlight (Invited)

NASA Astrophysics Data System (ADS)

Clover, J. M.; Jackson, B. V.; Buffington, A.; Hick, P. P.; Bisi, M. M.; Tokumaru, M.; Fujiki, K.

2010-12-01

The Solar Mass Ejection Imager (SMEI) observes Thomson-scattered white light from heliospheric electrons across almost all of the sky nearly all of the time since early 2003. Interplanetary scintillation (IPS) observations of velocity and g-level provide similar structure information but with a less-complete sky-and-time coverage. The Solar TErrestrial RElations Observatory (STEREO) twin spacecraft outer Heliospheric Imagers (HI-2) currently image the heliosphere in Thomson-scattered light near the ecliptic plane far from Earth. The Solar-Terrestrial Environment Laboratory (STELab) IPS observations provide IPS velocity and g-level values, which in conjunction with our tomographic reconstruction program, yield velocities and densities of the inner heliosphere in three dimensions. The same tomographic program substitutes SMEI Thomson-scattering brightness information for the g-level values to derive heliospheric densities from these data alone. We look at the global structure of the heliosphere concentrating mainly on three events from 2007 through the rise phase of Solar Cycle 24. The first event, observed in both the IPS and SMEI defines the three-dimensional velocity and density structure around the time of the shock observed at Earth on 02:02 UT 17 December 2007. The second event, seen only by SMEI, is that of the 23-26 April 2008 coronal mass ejection (CME) and its interplanetary counterpart. The third event is the CME (and its interplanetary counterpart) that took place 17 January 2010 and arrived at STEREO-B about four days later. For each event, we isolate the particular portion of the heliosphere attributed to the transient density structure using our tomographic technique, and then estimate its extent.

Individual structural differences in left inferior parietal area are associated with schoolchildrens' arithmetic scores

PubMed Central

Li, Yongxin; Hu, Yuzheng; Wang, Yunqi; Weng, Jian; Chen, Feiyan

2013-01-01

Arithmetic skill is of critical importance for academic achievement, professional success and everyday life, and childhood is the key period to acquire this skill. Neuroimaging studies have identified that left parietal regions are a key neural substrate for representing arithmetic skill. Although the relationship between functional brain activity in left parietal regions and arithmetic skill has been studied in detail, it remains unclear about the relationship between arithmetic achievement and structural properties in left inferior parietal area in schoolchildren. The current study employed a combination of voxel-based morphometry (VBM) for high-resolution T1-weighted images and fiber tracking on diffusion tensor imaging (DTI) to examine the relationship between structural properties in the inferior parietal area and arithmetic achievement in 10-year-old schoolchildren. VBM of the T1-weighted images revealed that individual differences in arithmetic scores were significantly and positively correlated with the gray matter (GM) volume in the left intraparietal sulcus (IPS). Fiber tracking analysis revealed that the forceps major, left superior longitudinal fasciculus (SLF), bilateral inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF) were the primary pathways connecting the left IPS with other brain areas. Furthermore, the regression analysis of the probabilistic pathways revealed a significant and positive correlation between the fractional anisotropy (FA) values in the left SLF, ILF and bilateral IFOF and arithmetic scores. The brain structure-behavior correlation analyses indicated that the GM volumes in the left IPS and the FA values in the tract pathways connecting left IPS were both related to children's arithmetic achievement. The present findings provide evidence that individual structural differences in the left IPS are associated with arithmetic scores in schoolchildren. PMID:24367320

Analytical method development and validation of simultaneous estimation of rabeprazole, pantoprazole, and itopride by reverse-phase high-performance liquid chromatography.

PubMed

Perumal, Senthamil Selvan; Ekambaram, Sanmuga Priya; Raja, Samundeswari

2014-12-01

A simple, selective, rapid, and precise reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous estimation of rabeprazole (RP), pantoprazole (PP), and itopride (IP) has been developed. The compounds were well separated on a Phenomenex C 18 (Luna) column (250 mm × 4.6 mm, dp = 5 μm) with C 18 guard column (4 mm × 3 mm × 5 μm) with a mobile phase consisting of buffer containing 10 mM potassium dihydrogen orthophosphate (adjusted to pH 6.8): acetonitrile (70:30 v/v) at a flow rate of 1.0 mL/min and ultraviolet detection at 288 nm. The retention time of RP, PP, and IP were 5.35, 7.92, and 11.16 minutes, respectively. Validation of the proposed method was carried out according to International Conference on Harmonisation (ICH) guidelines. Linearity range was obtained for RP, PP, and IP over the concentration range of 2.5-25, 1-30, and 3-35 μg/mL and the r 2 values were 0.994, 0.978, and 0.991, respectively. The calculated limit of detection (LOD) values were 1, 0.3, and 1 μg/mL and limit of quantitation (LOQ) values were 2.5, 1, and 3 μg/mL for RP, PP, and IP correspondingly. Thus, the current study showed that the developed reverse-phase liquid chromatography method is sensitive and selective for the estimation of RP, PP, and IP in combined dosage form. Copyright © 2014. Published by Elsevier B.V.

Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia.

PubMed

Adriaens, Michiel E; Prickaerts, Peggy; Chan-Seng-Yue, Michelle; van den Beucken, Twan; Dahlmans, Vivian E H; Eijssen, Lars M; Beck, Timothy; Wouters, Bradly G; Voncken, Jan Willem; Evelo, Chris T A

2016-01-01

A comprehensive assessment of the epigenetic dynamics in cancer cells is the key to understanding the molecular mechanisms underlying cancer and to improving cancer diagnostics, prognostics and treatment. By combining genome-wide ChIP-seq epigenomics and microarray transcriptomics, we studied the effects of oxygen deprivation and subsequent reoxygenation on histone 3 trimethylation of lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in a breast cancer cell line, serving as a model for abnormal oxygenation in solid tumors. A priori, epigenetic markings and gene expression levels not only are expected to vary greatly between hypoxic and normoxic conditions, but also display a large degree of heterogeneity across the cell population. Where traditionally ChIP-seq data are often treated as dichotomous data, the model and experiment here necessitate a quantitative, data-driven analysis of both datasets. We first identified genomic regions with sustained epigenetic markings, which provided a sample-specific reference enabling quantitative ChIP-seq data analysis. Sustained H3K27me3 marking was located around centromeres and intergenic regions, while sustained H3K4me3 marking is associated with genes involved in RNA binding, translation and protein transport and localization. Dynamic marking with both H3K4me3 and H3K27me3 (hypoxia-induced bivalency) was found in CpG-rich regions at loci encoding factors that control developmental processes, congruent with observations in embryonic stem cells. In silico -identified epigenetically sustained and dynamic genomic regions were confirmed through ChIP-PCR in vitro, and obtained results are corroborated by published data and current insights regarding epigenetic regulation.

Dendritic A-type potassium channel subunit expression in CA1 hippocampal interneurons.

PubMed

Menegola, M; Misonou, H; Vacher, H; Trimmer, J S

2008-06-26

Voltage-gated potassium (Kv) channels are important and diverse determinants of neuronal excitability and exhibit specific expression patterns throughout the brain. Among Kv channels, Kv4 channels are major determinants of somatodendritic A-type current and are essential in controlling the amplitude of backpropagating action potentials (BAPs) into neuronal dendrites. BAPs have been well studied in a variety of neurons, and have been recently described in hippocampal and cortical interneurons, a heterogeneous population of GABAergic inhibitory cells that regulate activity of principal cells and neuronal networks. We used well-characterized mouse monoclonal antibodies against the Kv4.3 and potassium channel interacting protein (KChIP) 1 subunits of A-type Kv channels, and antibodies against different interneuron markers in single- and double-label immunohistochemistry experiments to analyze the expression patterns of Kv4.3 and KChIP1 in hippocampal Ammon's horn (CA1) neurons. Immunohistochemistry was performed on 40 mum rat brain sections using nickel-enhanced diaminobenzidine staining or multiple-label immunofluorescence. Our results show that Kv4.3 and KChIP1 component subunits of A-type channels are co-localized in the soma and dendrites of a large number of GABAergic hippocampal interneurons. These subunits co-localize extensively but not completely with markers defining the four major interneuron subpopulations tested (parvalbumin, calbindin, calretinin, and somatostatin). These results suggest that CA1 hippocampal interneurons can be divided in two groups according to the expression of Kv4.3/KChIP1 channel subunits. Antibodies against Kv4.3 and KChIP1 represent an important new tool for identifying a subpopulation of hippocampal interneurons with a unique dendritic A-type channel complement and ability to control BAPs.

Mapping of transcription factor binding regions in mammalian cells by ChIP: Comparison of array- and sequencing-based technologies

PubMed Central

Euskirchen, Ghia M.; Rozowsky, Joel S.; Wei, Chia-Lin; Lee, Wah Heng; Zhang, Zhengdong D.; Hartman, Stephen; Emanuelsson, Olof; Stolc, Viktor; Weissman, Sherman; Gerstein, Mark B.; Ruan, Yijun; Snyder, Michael

2007-01-01

Recent progress in mapping transcription factor (TF) binding regions can largely be credited to chromatin immunoprecipitation (ChIP) technologies. We compared strategies for mapping TF binding regions in mammalian cells using two different ChIP schemes: ChIP with DNA microarray analysis (ChIP-chip) and ChIP with DNA sequencing (ChIP-PET). We first investigated parameters central to obtaining robust ChIP-chip data sets by analyzing STAT1 targets in the ENCODE regions of the human genome, and then compared ChIP-chip to ChIP-PET. We devised methods for scoring and comparing results among various tiling arrays and examined parameters such as DNA microarray format, oligonucleotide length, hybridization conditions, and the use of competitor Cot-1 DNA. The best performance was achieved with high-density oligonucleotide arrays, oligonucleotides ≥50 bases (b), the presence of competitor Cot-1 DNA and hybridizations conducted in microfluidics stations. When target identification was evaluated as a function of array number, 80%–86% of targets were identified with three or more arrays. Comparison of ChIP-chip with ChIP-PET revealed strong agreement for the highest ranked targets with less overlap for the low ranked targets. With advantages and disadvantages unique to each approach, we found that ChIP-chip and ChIP-PET are frequently complementary in their relative abilities to detect STAT1 targets for the lower ranked targets; each method detected validated targets that were missed by the other method. The most comprehensive list of STAT1 binding regions is obtained by merging results from ChIP-chip and ChIP-sequencing. Overall, this study provides information for robust identification, scoring, and validation of TF targets using ChIP-based technologies. PMID:17568005

IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X-ray crystallography

PubMed Central

Hamada, Kozo; Miyatake, Hideyuki; Terauchi, Akiko; Mikoshiba, Katsuhiko

2017-01-01

The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an IP3-gated ion channel that releases calcium ions (Ca2+) from the endoplasmic reticulum. The IP3-binding sites in the large cytosolic domain are distant from the Ca2+ conducting pore, and the allosteric mechanism of how IP3 opens the Ca2+ channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP3R in the absence and presence of IP3. Analyses of two distinct space group crystals uncovered an IP3-dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and channel domains. Mutagenesis of the IP3R channel revealed an essential role of a leaflet structure in the α-helical domain. These results suggest that the curvature α-helical domain relays IP3-controlled global conformational dynamics to the channel through the leaflet, conferring long-range allosteric coupling from IP3 binding to the Ca2+ channel. PMID:28416699

Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs.

PubMed

Shah, P C; Trivedi, N A; Bhatt, J D; Hemavathi, K G

2006-01-01

The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.

Potassium Channel Interacting Protein 2 (KChIP2) is not a transcriptional regulator of cardiac electrical remodeling

PubMed Central

Winther, Sine V.; Tuomainen, Tomi; Borup, Rehannah; Tavi, Pasi; Antoons, Gudrun; Thomsen, Morten B.

2016-01-01

The heart-failure relevant Potassium Channel Interacting Protein 2 (KChIP2) augments CaV1.2 and KV4.3. KChIP3 represses CaV1.2 transcription in cardiomyocytes via interaction with regulatory DNA elements. Hence, we tested nuclear presence of KChIP2 and if KChIP2 translocates into the nucleus in a Ca2+ dependent manner. Cardiac biopsies from human heart-failure patients and healthy donor controls showed that nuclear KChIP2 abundance was significantly increased in heart failure; however, this was secondary to a large variation of total KChIP2 content. Administration of ouabain did not increase KChIP2 content in nuclear protein fractions in anesthetized mice. KChIP2 was expressed in cell lines, and Ca2+ ionophores were applied in a concentration- and time-dependent manner. The cell lines had KChIP2-immunoreactive protein in the nucleus in the absence of treatments to modulate intracellular Ca2+ concentration. Neither increasing nor decreasing intracellular Ca2+ concentrations caused translocation of KChIP2. Microarray analysis did not identify relief of transcriptional repression in murine KChIP2−/− heart samples. We conclude that although there is a baseline presence of KChIP2 in the nucleus both in vivo and in vitro, KChIP2 does not directly regulate transcriptional activity. Moreover, the nuclear transport of KChIP2 is not dependent on Ca2+. Thus, KChIP2 does not function as a conventional transcription factor in the heart. PMID:27349185

One Approach for Transitioning the iNET Standards into the IRIG 106 Telemetry Standards

DTIC Science & Technology

2015-05-26

Protocol Suite. Figure 1 illustrates the Open Systems Interconnection ( OSI ) Model, the corresponding TCP/IP Model, and the major components of the TCP...IP Protocol Suite. Figure 2 represents the iNET-specific protocols layered onto the TCP/IP Model. Figure 1. OSI and TCP/IP Model with TCP/IP...Protocol Suite TCP/IP Protocol Suite Major Components IPv4 IPv6 TCP/IP Model OSI Model Application Presentation

Attraction of Southern Pine Engravers and Associated Bark Beetles (Coleoptera: Scolytidae) to Ipsenol, Ipsdienol, and Lanierone in Southeastern United States

Treesearch

D. R. Miller; C. Asaro; C. W. Berisford

2005-01-01

We determined the response of the small southern pine engraver, Ips avulses (Eichhoff); eastern fivespined ips, Ips grandicollis (Eichhoff); sixspined ips, Ips calligraphus (Germar); and pine engraver, Ips pini (Say) to the pheromones (±)-ipsenol, (±)-ipsdienol, and lanierone in the...

78 FR 49693 - Speech-to-Speech and Internet Protocol (IP) Speech-to-Speech Telecommunications Relay Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-15

...] Speech-to-Speech and Internet Protocol (IP) Speech-to-Speech Telecommunications Relay Services...: This is a summary of the Commission's Speech-to-Speech and Internet Protocol (IP) Speech-to-Speech...), Internet Protocol Relay (IP Relay), and IP captioned telephone service (IP CTS) as compensable forms of TRS...

Impact of artifact removal on ChIP quality metrics in ChIP-seq and ChIP-exo data

PubMed Central

Carroll, Thomas S.; Liang, Ziwei; Salama, Rafik; Stark, Rory; de Santiago, Ines

2014-01-01

With the advent of ChIP-seq multiplexing technologies and the subsequent increase in ChIP-seq throughput, the development of working standards for the quality assessment of ChIP-seq studies has received significant attention. The ENCODE consortium's large scale analysis of transcription factor binding and epigenetic marks as well as concordant work on ChIP-seq by other laboratories has established a new generation of ChIP-seq quality control measures. The use of these metrics alongside common processing steps has however not been evaluated. In this study, we investigate the effects of blacklisting and removal of duplicated reads on established metrics of ChIP-seq quality and show that the interpretation of these metrics is highly dependent on the ChIP-seq preprocessing steps applied. Further to this we perform the first investigation of the use of these metrics for ChIP-exo data and make recommendations for the adaptation of the NSC statistic to allow for the assessment of ChIP-exo efficiency. PMID:24782889

Alternative Oxidase Transcription Factors AOD2 and AOD5 of Neurospora crassa Control the Expression of Genes Involved in Energy Production and Metabolism.

PubMed

Qi, Zhigang; Smith, Kristina M; Bredeweg, Erin L; Bosnjak, Natasa; Freitag, Michael; Nargang, Frank E

2017-02-09

In Neurospora crassa , blocking the function of the standard mitochondrial electron transport chain results in the induction of an alternative oxidase (AOX). AOX transfers electrons directly from ubiquinol to molecular oxygen. AOX serves as a model of retrograde regulation since it is encoded by a nuclear gene that is regulated in response to signals from mitochondria. The N. crassa transcription factors AOD2 and AOD5 are necessary for the expression of the AOX gene. To gain insight into the mechanism by which these factors function, and to determine if they have roles in the expression of additional genes in N. crassa , we constructed strains expressing only tagged versions of the proteins. Cell fractionation experiments showed that both proteins are localized to the nucleus under both AOX inducing and noninducing conditions. Furthermore, chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) analysis revealed that the proteins are bound to the promoter region of the AOX gene under both conditions. ChIP-seq also showed that the transcription factors bind to the upstream regions of a number of genes that are involved in energy production and metabolism. Dependence on AOD2 and AOD5 for the expression of several of these genes was verified by quantitative PCR. The majority of ChIP-seq peaks observed were enriched for both AOD2 and AOD5. However, we also observed occasional sites where one factor appeared to bind preferentially. The most striking of these was a conserved sequence that bound large amounts of AOD2 but little AOD5. This sequence was found within a 310 bp repeat unit that occurs at several locations in the genome. Copyright © 2017 Qi et al.

Pain management by a new series of dual inhibitors of enkephalin degrading enzymes: long lasting antinociceptive properties and potentiation by CCK2 antagonist or methadone.

PubMed

Le Guen, Stéphanie; Mas Nieto, Magdalena; Canestrelli, Corinne; Chen, Huixiong; Fournié-Zaluski, Marie-Claude; Cupo, Annie; Maldonado, Rafaël; Roques, Bernard P; Noble, Florence

2003-07-01

The discovery that the endogenous morphine-like peptides named enkephalins are inactivated by two metallopeptidases, neutral endopeptidase and aminopeptidase N, which can be blocked by dual inhibitors, represents a promising way to develop 'physiological' analgesics devoid of the side effects of morphine. A new series of dual aminophosphinic inhibitors of the two enkephalin-catabolizing enzymes has been recently designed. In this study, one of these inhibitors, RB3007, was tested in various assays commonly used to select analgesics (mouse hot-plate test, rat tail-flick test, writhing and formalin tests in mice, and paw pressure test in rats), and the extracellular levels of the endogenous enkephalins in the ventrolateral periaqueductal grey have been measured by microdialysis after systemic administration of RB3007. In the mouse hot-plate test, the dual inhibitor induced long-lasting (2 h) antinociceptive effects with a maximum of 35% analgesia 60 min after i.v. or i.p. administration. These antinociceptive responses were antagonized by prior injection of naloxone (0.1 mg/kg, s.c.). Similar long lasting effects were observed in the other animal models used. Very interestingly, injection of RB3007 (50 mg/kg, i.p.) significantly increased (82%) the extracellular levels of Met-enkephalin with a peak 60 min after i.p. injection. This increase parallels the antinociceptive responses observed. In addition, strong facilitatory effects of subanalgesic doses of the CCK(2) receptor antagonist, PD-134,308 or the synthetic opioid agonist, methadone on RB3007-induced antinociceptive responses were observed. These findings may constitute promising data for future development of a new class of analgesics that could be of major interest in a number of severe and persistent pain syndromes.

Immunoendocrine alterations following Marine Corps Martial Arts training are associated with changes in moral cognitive processes.

PubMed

Siedlik, Jacob A; Deckert, Jake A; Clopton, Aaron W; Gigliotti, Nicole; Chan, Marcia A; Benedict, Stephen H; Herda, Trent J; Gallagher, Philip M; Vardiman, John P

2016-02-01

Combined physical and psychological stress events have been associated with exacerbated endocrine responses and increased alterations in immune cell trafficking when compared to exercise stress alone. Military training programs are rigorous in nature and often purposefully delivered in environments combining high levels of both physical and mental stress. The objective of this study was to assess physiological and cognitive changes following U.S. Marine Corps Martial Arts training. Seven active-duty, male Marines were observed during a typical Marine Corps Martial Arts training session. Immune parameters, including immunomodulatory cytokines, and hormone concentrations were determined from blood samples obtained at baseline, immediately post training (IP) and at 15min intervals post-training to 1h (R15, R30, R45, R60). Assessments of cognitive moral functioning (moral judgment and intent) were recorded at intervals during recovery. There were significant fluctuations in immunoendocrine parameters. Peak endocrine measures were observed within the IP-R15 time interval. Distributions of circulating immune cells were significantly altered with neutrophils and all lymphocyte subsets elevated at IP. IFN-γ and IL-17a exhibited small, non-significant, parallel increases over the recovery period. Moral functioning was informed by different social identities during the recovery resulting in changes in moral decision-making. These data demonstrate that the Marine Corps Martial Arts Program induces significant alterations in lymphocyte and leukocyte distributions, but does not shift the balance of Th1/Th2 cytokines or induce a systemic inflammatory response. The program does, however, induce alterations in moral decision-making ability associated with the observed endocrine responses, even suggesting a potential interaction between one's social identities and endocrine responses upon moral decision-making. Copyright © 2015. Published by Elsevier Inc.

SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters.

PubMed

Oh, Chun-do; Lu, Yue; Liang, Shoudan; Mori-Akiyama, Yuko; Chen, Di; de Crombrugghe, Benoit; Yasuda, Hideyo

2014-01-01

The transcription factor SOX9 plays an essential role in determining the fate of several cell types and is a master factor in regulation of chondrocyte development. Our aim was to determine which genes in the genome of chondrocytes are either directly or indirectly controlled by SOX9. We used RNA-Seq to identify genes whose expression levels were affected by SOX9 and used SOX9 ChIP-Seq to identify those genes that harbor SOX9-interaction sites. For RNA-Seq, the RNA expression profile of primary Sox9flox/flox mouse chondrocytes infected with Ad-CMV-Cre was compared with that of the same cells infected with a control adenovirus. Analysis of RNA-Seq data indicated that, when the levels of Sox9 mRNA were decreased more than 8-fold by infection with Ad-CMV-Cre, 196 genes showed a decrease in expression of at least 4-fold. These included many cartilage extracellular matrix (ECM) genes and a number of genes for ECM modification enzymes (transferases), membrane receptors, transporters, and others. In ChIP-Seq, 75% of the SOX9-interaction sites had a canonical inverted repeat motif within 100 bp of the top of the peak. SOX9-interaction sites were found in 55% of the genes whose expression was decreased more than 8-fold in SOX9-depleted cells and in somewhat fewer of the genes whose expression was reduced more than 4-fold, suggesting that these are direct targets of SOX9. The combination of RNA-Seq and ChIP-Seq has provided a fuller understanding of the SOX9-controlled genetic program of chondrocytes.

A mechanism for upper airway stability during slow wave sleep.

PubMed

McSharry, David G; Saboisky, Julian P; Deyoung, Pam; Matteis, Paul; Jordan, Amy S; Trinder, John; Smales, Erik; Hess, Lauren; Guo, Mengshuang; Malhotra, Atul

2013-04-01

The severity of obstructive sleep apnea is diminished (sometimes markedly) during slow wave sleep (SWS). We sought to understand why SWS stabilizes the upper airway. Increased single motor unit (SMU) activity of the major upper airway dilating muscle (genioglossus) should improve upper airway stability. Therefore, we hypothesized that genioglossus SMUs would increase their activity during SWS in comparison with Stage N2 sleep. The activity of genioglossus SMUs was studied on both sides of the transition between Stage N2 sleep and SWS. Sleep laboratory. Twenty-nine subjects (age 38 ± 13 yr, 17 males) were studied. SWS. Subjects slept overnight with fine-wire electrodes in their genioglossus muscles and with full polysomnographic and end tidal carbon dioxide monitors. Fifteen inspiratory phasic (IP) and 11 inspiratory tonic (IT) units were identified from seven subjects and these units exhibited significantly increased inspiratory discharge frequencies during SWS compared with Stage N2 sleep. The peak discharge frequency of the inspiratory units (IP and IT) was 22.7 ± 4.1 Hz in SWS versus 20.3 ± 4.5 Hz in Stage N2 (P < 0.001). The IP units also fired for a longer duration (expressed as a percentage of inspiratory time) during SWS (104.6 ± 39.5 %TI) versus Stage N2 sleep (82.6 ± 39.5 %TI, P < 0.001). The IT units fired faster during expiration in SWS (14.2 ± 1.8 Hz) versus Stage N2 sleep (12.6 ± 3.1 Hz, P = 0.035). There was minimal recruitment or derecruitment of units between SWS and Stage N2 sleep. Increased genioglossus SMU activity likely makes the airway more stable and resistant to collapse throughout the respiratory cycle during SWS.

Inositol trisphosphate metabolism in carrot (Daucus carota L. ) cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Memon, A.R.; Rincon, M.; Boss, W.F.

1989-10-01

The metabolism of exogenously added D-myo-(1-{sup 3}H)inositol 1,4,5-trisphosphate (IP{sub 3}) has been examined in microsomal membrane and soluble fractions of carrot cells grown in suspension culture. When ({sup 3}H)IP{sub 3} was added to a microsomal membrane fraction, ({sup 3}H)IP{sub 2} was the primary metabolite consisting of approximately 83% of the total recovered ({sup 3}H) by electrophoresis. ({sup 3}H)IP was only 6% of the ({sup 3}H) recovered, and 10% of the ({sup 3}H)IP{sub 3} was not further metabolized. In contrast, when ({sup 3}H)IP{sub 3} was added to the soluble fraction, approximately equal amounts of ({sup 3}H)IP{sub 2} and ({sup 3}H)IP weremore » recovered. Ca{sup 2+} (100 micromolar) tended to enhance IP{sub 3} dephosphorylation but inhibited the IP{sub 2} dephosphorylation in the soluble fraction by about 20%. MoO{sub 4}{sup 2{minus}} (1 millimolar) inhibited the dephosphorylation of IP{sub 3} by the microsomal fraction and the dephosphorylation of IP{sub 2} by the soluble fraction. MoO{sub 4}{sup 2{minus}}, however, did not inhibit the dephosphorylation of IP{sub 3} by the soluble fraction. Li{sup +} (10 and 50 millimolar) had no effect on IP{sub 3} metabolism in either the soluble or membrane fraction; however, Li{sup +} (50 millimolar) inhibited IP{sub 2} dephosphorylation in the soluble fraction about 25%.« less

Properties of micro-arc oxidation coatings on aluminum alloy at different negative peak current densities

NASA Astrophysics Data System (ADS)

Gu, Xin; Jiang, Bailing; Li, Hongtao; Liu, Cancan; Shao, Lianlian

2018-05-01

Micro-arc oxidation coatings were fabricated on 6061 aluminum alloy using whereby bipolar pulse mode in the case of different negative peak current densities. The phase composition, microstructures and wear properties were studied using x-ray diffraction, scanning electron microscopy and ball-on-disk wear tester, respectively. As results indicate, by virtue of negative peak current density, the oxygen can be expelled by produced hydrogen on anode in the case of negative pulse width and via the opened discharge channel. The results of x-ray diffraction, surface and cross-sectional morphology indicated that the coating was structured compactly taking on less small-diameter micro-pores and defects with negative peak current density of 75 A dm‑2. Additionally, as the results of wear tracks and weight loss bespeak, by virtue of appropriate negative peak current density, coatings resisted the abrasive wear and showed excellent wear resistance.

Mission Applicability Assessment of Integrated Power Components and Systems

NASA Technical Reports Server (NTRS)

Raffaelle, R. P.; Hepp, A. F.; Landis, G. A.; Hoffman, D. J.

2002-01-01

The need for smaller lightweight autonomous power systems has recently increased with the increasing focus on micro- and nanosatellites. Small area high-efficiency thin film batteries and solar cells are an attractive choice for such applications. The NASA Glenn Research Center, Johns Hopkins Applied Physics Laboratory, Lithium Power Technologies, MicroSat Systems, and others, have been working on the development of autonomous monolithic packages combining these elements or what are called integrated power supplies (IPS). These supplies can be combined with individual satellite components and are capable of providing continuous power even under intermittent illumination associated with a spinning or Earth orbiting satellite. This paper discusses the space mission applicability, benefits, and current development efforts associated with integrated power supply components and systems. The characteristics and several mission concepts for an IPS that combines thin-film photovoltaic power generation with thin-film lithium ion energy storage are described. Based on this preliminary assessment, it is concluded that the most likely and beneficial application of an IPS will be for small "nanosatellites" or in specialized applications serving as a decentralized or as a distributed power source or uninterruptible power supply.

Machine Learning Approach to Automated Quality Identification of Human Induced Pluripotent Stem Cell Colony Images.

PubMed

Joutsijoki, Henry; Haponen, Markus; Rasku, Jyrki; Aalto-Setälä, Katriina; Juhola, Martti

2016-01-01

The focus of this research is on automated identification of the quality of human induced pluripotent stem cell (iPSC) colony images. iPS cell technology is a contemporary method by which the patient's cells are reprogrammed back to stem cells and are differentiated to any cell type wanted. iPS cell technology will be used in future to patient specific drug screening, disease modeling, and tissue repairing, for instance. However, there are technical challenges before iPS cell technology can be used in practice and one of them is quality control of growing iPSC colonies which is currently done manually but is unfeasible solution in large-scale cultures. The monitoring problem returns to image analysis and classification problem. In this paper, we tackle this problem using machine learning methods such as multiclass Support Vector Machines and several baseline methods together with Scaled Invariant Feature Transformation based features. We perform over 80 test arrangements and do a thorough parameter value search. The best accuracy (62.4%) for classification was obtained by using a k-NN classifier showing improved accuracy compared to earlier studies.

IP-Based Video Modem Extender Requirements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierson, L G; Boorman, T M; Howe, R E

2003-12-16

Visualization is one of the keys to understanding large complex data sets such as those generated by the large computing resources purchased and developed by the Advanced Simulation and Computing program (aka ASCI). In order to be convenient to researchers, visualization data must be distributed to offices and large complex visualization theaters. Currently, local distribution of the visual data is accomplished by distance limited modems and RGB switches that simply do not scale to hundreds of users across the local, metropolitan, and WAN distances without incurring large costs in fiber plant installation and maintenance. Wide Area application over the DOEmore » Complex is infeasible using these limited distance RGB extenders. On the other hand, Internet Protocols (IP) over Ethernet is a scalable well-proven technology that can distribute large volumes of data over these distances. Visual data has been distributed at lower resolutions over IP in industrial applications. This document describes requirements of the ASCI program in visual signal distribution for the purpose of identifying industrial partners willing to develop products to meet ASCI's needs.« less

Stimulation of Inositol 1,4,5-Trisphosphate (IP3) Receptor Subtypes by Adenophostin A and Its Analogues

PubMed Central

Saleem, Huma; Tovey, Stephen C.; Riley, Andrew M.; Potter, Barry V. L.; Taylor, Colin W.

2013-01-01

Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular Ca2+ channels. Most animal cells express mixtures of the three IP3R subtypes encoded by vertebrate genomes. Adenophostin A (AdA) is the most potent naturally occurring agonist of IP3R and it shares with IP3 the essential features of all IP3R agonists, namely structures equivalent to the 4,5-bisphosphate and 6-hydroxyl of IP3. The two essential phosphate groups contribute to closure of the clam-like IP3-binding core (IBC), and thereby IP3R activation, by binding to each of its sides (the α- and β-domains). Regulation of the three subtypes of IP3R by AdA and its analogues has not been examined in cells expressing defined homogenous populations of IP3R. We measured Ca2+ release evoked by synthetic adenophostin A (AdA) and its analogues in permeabilized DT40 cells devoid of native IP3R and stably expressing single subtypes of mammalian IP3R. The determinants of high-affinity binding of AdA and its analogues were indistinguishable for each IP3R subtype. The results are consistent with a cation-π interaction between the adenine of AdA and a conserved arginine within the IBC α-domain contributing to closure of the IBC. The two complementary contacts between AdA and the α-domain (cation-π interaction and 3″-phosphate) allow activation of IP3R by an analogue of AdA (3″-dephospho-AdA) that lacks a phosphate group equivalent to the essential 5-phosphate of IP3. These data provide the first structure-activity analyses of key AdA analogues using homogenous populations of all mammalian IP3R subtypes. They demonstrate that differences in the Ca2+ signals evoked by AdA analogues are unlikely to be due to selective regulation of IP3R subtypes. PMID:23469136

Biomonitoring the Cooked Meat Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Hair: Impact of Exposure, Pigmentation and Cytochrome P450 1A2 Phenotype

PubMed Central

Turesky, Robert J.; Liu, Lin; Gu, Dan; Yonemori, Kim M.; White, Kami K.; Wilkens, Lynne R.; Marchand, Loic Le

2013-01-01

Background Hair is a promising tissue to assess exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen formed in cooked meats. However, an understanding of how dietary exposure to PhIP, cytochrome P450 1A2 activity - a key enzyme involved in PhIP metabolism, and hair pigmentation affect the level of PhIP accrued in hair is required in order to determine the reliability of the PhIP hair level as a biomarker of exposure to this carcinogen. Methods We examined the impact of PhIP exposure, cytochrome P450 1A2 activity, and hair pigmentation on the levels of PhIP accumulated in the hair of volunteers on a 4-week semi-controlled diet of cooked meat containing known quantities of PhIP. Results The amount of PhIP in hair increased, on average, 15-fold in light- and dark-haired individuals during consumption of cooked meat. PhIP levels in hair were correlated to PhIP intake (ρ = 0.53; p < 0.001), and the relationship was strengthened when PhIP levels were normalized for the melanin content of hair (ρ = 0.71; p < 0.001). However, PhIP accrual in hair was not correlated to cytochrome P450 1A2 activity, as assessed by the caffeine test, or to the levels of unmetabolized PhIP in urine, or to the metabolic ratio of the major urinary metabolite N2-(ß-1-glucosiduronyl-2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine to unmetabolized PhIP. Conclusions The employment of the PhIP hair biomarker should take hair pigmentation into account for accurate exposure assessment. Impact PhIP hair levels can serve as a biomarker in epidemiological studies investigating the association of HAAs, cooked meat and cancer risk. PMID:23329727

Biomonitoring the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in hair: impact of exposure, hair pigmentation, and cytochrome P450 1A2 phenotype.

PubMed

Turesky, Robert J; Liu, Lin; Gu, Dan; Yonemori, Kim M; White, Kami K; Wilkens, Lynne R; Le Marchand, Loïc

2013-03-01

Hair is a promising tissue to assess exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen formed in cooked meats. However, an understanding of how dietary exposure to PhIP, cytochrome P450 1A2 activity-a key enzyme involved in PhIP metabolism, and hair pigmentation affect the level of PhIP accrued in hair is required to determine the reliability of the PhIP hair level as a biomarker of exposure to this carcinogen. We examined the impact of PhIP exposure, cytochrome P450 1A2 activity, and hair pigmentation on the levels of PhIP accumulated in the hair of volunteers on a 4-week semicontrolled diet of cooked meat containing known quantities of PhIP. The amount of PhIP in hair increased, on average, 15-fold in light- and dark-haired individuals during consumption of cooked meat. PhIP levels in hair were correlated to PhIP intake (ρ = 0.53; P < 0.001), and the relationship was strengthened when PhIP levels were normalized for the melanin content of hair (ρ = 0.71; P < 0.001). However, PhIP accrual in hair was not correlated to cytochrome P450 1A2 activity, as assessed by the caffeine test, or to the levels of unmetabolized PhIP in urine or to the metabolic ratio of the major urinary metabolite N(2)-(β-1-glucosiduronyl-2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine to unmetabolized PhIP. The use of the PhIP hair biomarker should take hair pigmentation into account for accurate exposure assessment of PhIP. PhIP hair levels can serve as a biomarker in epidemiologic studies investigating the association of heterocyclic aromatic amine (HAA), cooked meat, and cancer risk.

Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats.

PubMed

Lindquist, Derick H; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E

2013-09-01

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink-conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4-9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 ms) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 ms) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus. Published by Elsevier Inc.

Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats

PubMed Central

Lindquist, Derick H.; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E.

2013-01-01

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4–9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 msec) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 msec) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus. PMID:23871534

Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, α1- and 5-HT2A-receptors

PubMed Central

Sebban, Claude; Tesolin-Decros, Brigitte; Ciprian-Ollivier, Jorge; Perret, Laurent; Spedding, Michael

2002-01-01

The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0 – 30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1 – 3 mg kg−1 s.c.) caused a marked dose-dependent increase in EEG power in the frontal cortex at 1 – 3 Hz with decreases in power at higher frequencies (9 – 30 Hz). At high doses (3 mg kg−1 s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05 – 0.1 mg kg−1 i.p.) caused similar effects but with lesser changes in power. In contrast, the non-competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1 – 10 mg kg−1 i.p.) The atypical antipsychotic clozapine (0.2 mg kg−1 s.c.) synchronized the EEG (peak 8 Hz). The 5-HT2A-antagonist, M100907, specifically increased EEG power at 2 – 3 Hz at low doses (10 and 50 μg kg÷1 s.c.), whereas at higher doses (0.1 mg kg−1 s.c.) the profile resembled that of clozapine. Clozapine (0.2 mg kg−1 s.c.), GYKI 53655 (5 mg kg−1 i.p.), prazosin (0.05 and 0.1 mg kg−1 i.p.), and M100907 (0.01 and 0.05 mg kg−1 s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg−1 s.c.), but not the increase in power at 1 – 3 Hz in prefrontal cortex. PMID:11786481

Neuroprotective effects of idebenone against pilocarpine-induced seizures: modulation of antioxidant status, DNA damage and Na(+), K (+)-ATPase activity in rat hippocampus.

PubMed

Ahmed, Maha Ali Eissa

2014-02-01

The current study investigated the neuroprotective activity of idebenone against pilocarpine-induced seizures and hippocampal injury in rats. Idebenone is a ubiquinone analog with antioxidant, and ATP replenishment effects. It is well tolerated and has low toxicity. Previous studies reported the protective effects of idebenone against neurodegenerative diseases such as Friedreich's ataxia and Alzheimer's disease. So far, the efficacy of idebenone in experimental models of seizures has not been tested. To achieve this aim, rats were randomly distributed into six groups. Two groups were treated with either normal saline (0.9 %, i.p., control group) or idebenone (200 mg/kg, i.p., Ideb200 group) for three successive days. Rats of the other four groups (P400, Ideb50 + P400, Ideb100 + P400, and Ideb200 + P400) received either saline or idebenone (50, 100, 200 mg/kg, i.p.) for 3 days, respectively followed by a single dose of pilocarpine (400 mg/kg, i.p.). All rats were observed for 6 h post pilocarpine injection. Latency to the first seizure, and percentages of seizures and survival were recorded. Surviving animals were sacrificed, and the hippocampal tissues were separated and used for the measurement of lipid peroxides, total nitrate/nitrite, glutathione and DNA fragmentation levels, in addition to catalase and Na(+), K(+)-ATPase activities. Results revealed that in a dose-dependent manner, idebenone (100, 200 mg/kg) prolonged the latency to the first seizure, elevated the percentage of survival and diminished the percentage of pilocapine-induced seizures in rats. Significant increases in lipid peroxides, total nitrate/nitrite, DNA fragmentation levels and catalase activity, in addition to a significant reduction in glutathione level and Na(+), K(+)-ATPase activity were observed in pilocarpine group. Pre-administration of idebenone (100, 200 mg/kg, i.p.) to pilocarpine-treated rats, significantly reduced lipid peroxides, total nitrate/nitrite, DNA fragmentation levels, and normalized catalase activity. Moreover, idebenone prevented pilocarpine-induced detrimental effects on brain hippocampal glutathione level, and Na(+), K(+)-ATPase enzyme activity in rats. Data obtained from the current investigation emphasized the critical role of oxidative stress in induction of seizures by pilocarpine and elucidated the prominent neuroprotective and antioxidant activities of idebenone in this model.

Spatial distributions of Kv4 channels and KChip2 isoforms in the murine heart based on laser capture microdissection.

PubMed

Teutsch, Christine; Kondo, Richard P; Dederko, Dorothy A; Chrast, Jacqueline; Chien, Kenneth R; Giles, Wayne R

2007-03-01

Regional differences in repolarizing K(+) current densities and expression levels of their molecular components are important for coordinating the pattern of electrical excitation and repolarization of the heart. The small size of hearts from mice may obscure these interventricular and/or transmural expression differences of K(+) channels. We have examined this possibility in adult mouse ventricle using a technology that provides very high spatial resolution of tissue collection. Conventional manual dissection and laser capture microdissection (LCM) were utilized to dissect tissue from distinct ventricular regions. RNA was isolated from epicardial, mid-myocardial and endocardial layers of both the right and left ventricles. Real-time RT-PCR was used to quantify the transcript expression in these different regions. LCM revealed significant interventricular and transmural gradients for both Kv4.2 and the alpha-subunit of KChIP2. The expression profile of a second K(+) channel transcript, Kir2.1, which is responsible for the inwardly rectifying K(+) current I(k1), showed no interventricular or transmural gradients and therefore served as a negative control. Our findings are in contrast to previous reports of a relatively uniform left ventricular transmural pattern of expression of Kv4.2, Kv4.3 and KChIP2 in adult mouse heart, which appear to be different than that in larger mammals. Specifically, our results demonstrate significant epi- to endocardial differences in the patterns of expression of both Kv4.2 and KChIP2.

Curcumin modifies Apc(min) apoptosis resistance and inhibits 2-amino 1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced tumour formation in Apc(min) mice.

PubMed

Collett, G P; Robson, C N; Mathers, J C; Campbell, F C

2001-05-01

Curcumin, the active ingredient of the rhizome of Curcuma longa, promotes apoptosis and may have chemopreventive properties. This study investigates the effects of curcumin on apoptosis and tumorigenesis in male Apc(min) mice treated with the human dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Intestinal epithelial apoptotic index in response to PhIP treatment was approximately twice as great in the wild-type C57BL/6 APC(+/+) strain than in Apc(min) mice (3.7% Apc(+/+) versus 1.9% Apc(min); P < 0.001). PhIP promoted tumour formation in Apc(min) proximal small intestine (4.6 tumours per mouse, PhIP treated versus 2.1 tumours per mouse, control untreated; P < 0.05). Curcumin enhanced PhIP-induced apoptosis (4.0% curcumin + PhIP versus 2.1% PhIP alone; P < 0.01) and inhibited PhIP-induced tumorigenesis in the proximal small intestine of Apc(min) mice (2.2 tumours per mouse, curcumin + PhIP versus 4.6 tumours per mouse PhIP alone; P < 0.05). This study shows that the Apc(min) genotype is associated with resistance to PhIP-induced apoptosis in intestinal epithelium. Curcumin attenuates Apc(min) resistance to PhIP-induced apoptosis and inhibits PhIP-induced tumorigenesis in proximal Apc(min) mouse small intestine.

Method and apparatus for clockless analog-to-digital conversion and peak detection

DOEpatents

DeGeronimo, Gianluigi

2007-03-06

An apparatus and method for analog-to-digital conversion and peak detection includes at least one stage, which includes a first switch, second switch, current source or capacitor, and discriminator. The discriminator changes state in response to a current or charge associated with the input signal exceeding a threshold, thereby indicating whether the current or charge associated with the input signal is greater than the threshold. The input signal includes a peak or a charge, and the converter includes a peak or charge detect mode in which a state of the switch is retained in response to a decrease in the current or charge associated with the input signal. The state of the switch represents at least a portion of a value of the peak or of the charge.

Video Surveillance: All Eyes Turn to IP

ERIC Educational Resources Information Center

Raths, David

2011-01-01

Many university officials recognize the need to upgrade their older analog video surveillance systems. In a 2010 survey by "Campus Safety" magazine, half of university respondents expressed dissatisfaction with the quality and coverage of their current video surveillance systems. Among the limitations of analog closed-circuit television…

Non-Solenoidal Tokamak Startup via Inboard Local Helicity Injection on the Pegasus ST

NASA Astrophysics Data System (ADS)

Perry, J. M.; Barr, J. L.; Bodner, G. M.; Bongard, M. W.; Fonck, R. J.; Pachicano, J. L.; Reusch, J. A.; Rodriguez Sanchez, C.; Richner, N. J.; Schlossberg, D. J.

2016-10-01

Local helicity injection (LHI) is a non-solenoidal startup technique utilizing small injectors at the plasma edge to source current along helical magnetic field lines. Unstable injected current streams relax to a tokamak-like configuration with high toroidal current multiplication. Flexible placement of injectors permits tradeoffs between helicity injection rate, poloidal field induction, and magnetic geometry requirements for initial relaxation. Experiments using a new set of large-area injectors in the lower divertor explore the efficacy of high-field-side (HFS) injection. The increased area (4 cm2) current source is functional up to full Pegasus toroidal field (BT , inj = 0.23 T). However, relaxation to a tokamak state is increasingly frustrated for BT , inj > 0.15 T with uniform vacuum vertical field. Paths to relaxation at increased field include: manipulation of vacuum poloidal field geometry; increased injector current; and plasma initiation with outboard injectors, subsequently transitioning to divertor injector drive. During initial tests of HFS injectors, achieved Vinj was limited to 600 V by plasma-material interactions on the divertor plate, which may be mitigated by increasing injector elevation. In experiments with helicity injection as the dominant current drive Ip 0.13 MA has been attained, with T̲e > 100 eV and ne 1019 m-3. Extrapolation to full BT, longer pulse length, and Vinj 1 kV suggest Ip > 0.25 MA should be attainable in a plasma dominated by helicity drive. Work supported by US DOE Grant DE-FG02-96ER54375.

Compressive Spectral Embedding: Sidestepping the SVD

DTIC Science & Technology

2015-09-28

of Rn, the distance between the p, q-th rows of f̃(S) can be written as ‖f̃L(S) (ip − iq)‖ = ‖f(S) (ip − iq)− Z (ip − iq)‖ ≤ ‖ ET (ip − iq)‖+ δ √ 2...2) Similarly, we have that ‖f̃L(S) (ip − iq)‖ ≥ ‖ ET (ip − iq)‖ − δ √ 2. Thus pairwise distances be- tween the rows of f̃L(S) approximate those between...iq) ∥∥∥ = ∥∥∥ΩT f̃L(S) (ip − iq) ∥∥∥ ≤ √ 1 + ǫ ∥∥∥f̃L(S) (ip − iq) ∥∥∥ Using (2), we can show that ‖ẼT (ip − iq)‖ ≤ √ 1 + ǫ ( ‖ ET (ip − iq)‖+ δ √ 2

The disposition of /sup 14/C-trimethyltin in the pregnant rat and fetus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipscomb, J.C.; Paule, M.G.; Slikker, W. Jr.

1989-03-01

Trimethyltin (TMT) is a potent neurotoxicant. For unknown reasons, age at exposure to TMT may dramatically influence the severity of TMT-induced neuropathology. We have demonstrated previously that radiolabel derived from (/sup 14/C)-TMT given to pregnant dams on gestational day (GD) 17 is found in fetal brain and blood. The present study was designed to determine the distribution of radiolabel derived from (14C)-TMT to brain and other tissue in fetuses from dams dosed on either GD 12 or 17 with 7.0 mg/kg TMT chloride. Radioactivity in GD 12 and GD 17 maternal whole blood peaked 1 hour after IP treatment. Wholemore » blood elimination half-lives were 12-15 days. Peak radiolabel concentrations in GD 12 maternal and fetal brain were only 11-30% of those from GD 17 animals, however, peak fetal brain concentrations of radiolabel were not different from their respective maternal brain concentrations. Radiolabel concentrations in liver, kidney, and adrenal of GD 17 dams were higher than those in corresponding GD 12 tissues. Combined urinary and fecal elimination of radiolabel for two weeks after dosing accounted for 31 and 22% of the GD 12 and 17 doses, respectively. It appears that gestational age influences the distribution and elimination of TMT in the rat.« less

Global Mapping of Cell Type–Specific Open Chromatin by FAIRE-seq Reveals the Regulatory Role of the NFI Family in Adipocyte Differentiation

PubMed Central

Yu, Jing; Hirose-Yotsuya, Lisa; Take, Kazumi; Sun, Wei; Iwabu, Masato; Okada-Iwabu, Miki; Fujita, Takanori; Aoyama, Tomohisa; Tsutsumi, Shuichi; Ueki, Kohjiro; Kodama, Tatsuhiko; Sakai, Juro; Aburatani, Hiroyuki; Kadowaki, Takashi

2011-01-01

Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type–specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation) and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq). FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPARγ and C/EBPα, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI) transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPARγ binding sites near PPARγ, C/EBPα, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA–mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our study demonstrates the utility of FAIRE-seq in providing a global view of cell type–specific regulatory elements in the genome and in identifying transcriptional regulators of adipocyte differentiation. PMID:22028663

Cross talk between cyclic AMP and the polyphosphoinositide signaling cascade in iris sphincter and other nonvascular smooth muscle.

PubMed

Abdel-Latif, A A

1996-02-01

Nonvascular smooth muscle, such as the iris sphincter, receives double reciprocal innervation: stimulation of the parasympathetic nervous system (cholinergic muscarinic), which functions through the polyphosphoinositide (PPI) signaling pathway, contracts it, while activation of the sympathetic nervous system (beta-adrenergic), which functions through the cAMP system, relaxes it. Interactions between the two second messenger systems are important in regulation of smooth muscle tone and represent an important focal point for pharmacological manipulation. Here, I have summarized the experimental evidence in support of the hypothesis that the cross talk between cAMP and the PPI cascade could constitute a biochemical correlate for this functional antagonism. Recent studies suggest that cAMP inhibition is on Ca2+ mobilization rather than myosin light chain phosphorylation. Thus, cAMP-elevating agents, which inhibit agonist-induced PPI hydrolysis, are effective relaxants. Furthermore, inositol 1,4,5-trisphosphate (IP3) appears to be involved in both Ca2+ release from the sarcoplasmic reticulum and in Ca2+ influx through the plasma membrane, and since a reduction in intracellular Ca2+ ([Ca2+]i) is the underlying mechanism for cAMP-mediated relaxation, an important target for cAMP inhibition would be either to inhibit IP3 production or to stimulate IP3 inactivation. In the iris sphincter and other nonvascular smooth muscle there is reasonable experimental evidence that shows that cAMP inhibits phospholipase C activation and stimulates IP3 3-kinase activity, both of which can result in: [i) reduction in IP3 concentrations and (ii) reduction in IP3-dependent Ca2+ mobilization, which may lead to muscle relaxation. In addition to IP3-induced Ca2+ mobilization, changes in [Ca2+]i are the result of the interplay of many processes which may also serve as potential sites for cAMP inhibition. A great deal of progress has been made on the cross talk between cAMP and the PPI signaling cascade in the past decade, and there will be more on the regulation of the second messenger systems and their involvement in smooth muscle tone in the coming years. Clearly, an understanding of the physiological and pathophysiological regulation of smooth muscle tone is central to the development of novel therapeutic agents for the treatment of diseases such as asthma and glaucoma, where cAMP-elevating drugs are currently employed.

Inlet patch: heterotopic gastric mucosa--another contributor to supraesophageal symptoms?

PubMed

Macha, Suhasini; Reddy, Sushma; Rabah, Raja; Thomas, Ronald; Tolia, Vasundhara

2005-09-01

To determine prospectively the incidence of an inlet patch (IP) in children requiring esophagogastroduodenoscopy (EGD) and assess the prevalence of presenting symptoms between children with and without an IP. All patients undergoing EGD in a 2-year period were assessed for the presence of an IP with biopsy confirmation. IP, distal esophagus, and stomach biopsy specimens were blindly reviewed by a pathologist for the presence and degree of inflammation and intestinal metaplasia. Symptoms from children with and without an IP were compared. From 407 EGDs done by a single endoscopist, 24 patients had confirmed IP (incidence of 5.9%). The presence and degree of inflammation were always relatively greater in the columnar mucosa of the IP than in the antral/body gastric mucosa in the same patient (P = .0027) Inflammation was similar in the squamous epithelium around the IP and in the distal esophagus (P=.46). Two patients had intestinal metaplasia of the IP. The patients with IPs had a higher prevalence of respiratory symptoms than the control group (P = .03). Children with IPs may have a higher frequency of respiratory symptoms. Periodic surveillance should be performed in children with intestinal metaplasia of an IP.

Use of the Empress all-ceramic restoration system.

PubMed

Goulet, M K

1997-01-01

New dental materials and techniques have been introduced in the past few years to fabricate aesthetic ceramic restorations with improved strength, biocompatibility, resistance to wear, and better fit. Aesthetic concerns and increasing demand for tooth-colored posterior restorations have led to a number of all-ceramic restorations such as IPS Empress (Ivoclar-Williams, Amherst, NY). The Empress system offers superior aesthetics and physical properties. New generation ceramics along with the current adhesive techniques have resulted in the ability to provide higher strength, therefore indicating crowns for posterior restorations as well. These materials are being used more frequently and in more extensive oral prosthetic rehabilitations such as the case that will be presented. We discuss the different properties and advantages of IPS Empress.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashimoto, Muneaki, E-mail: muneaki@juntendo.ac.jp; Nara, Takeshi, E-mail: tnara@juntendo.ac.jp; Enomoto, Masahiro, E-mail: menomoto@uhnres.utoronto.ca

Inositol 1,4,5-trisphosphate receptor (IP{sub 3}R) is a key regulator of intracellular Ca{sup 2+} concentration that release Ca{sup 2+} from Ca{sup 2+} stores in response to various external stimuli. IP{sub 3}R also works as a signal hub which form a platform for interacting with various proteins involved in diverse cell signaling. Previously, we have identified an IP{sub 3}R homolog in the parasitic protist, Trypanosoma cruzi (TcIP{sub 3}R). Parasites expressing reduced or increased levels of TcIP{sub 3}R displayed defects in growth, transformation, and infectivity. In the present study, we established parasitic strains expressing a dominant negative form of TcIP{sub 3}R, named DN-TcIP{submore » 3}R, to further investigate the physiological role(s) of TcIP{sub 3}R. We found that the growth of epimastigotes expressing DN-TcIP{sub 3}R was significantly slower than that of parasites with TcIP{sub 3}R expression levels that were approximately 65% of wild-type levels. The expression of DN-TcIP{sub 3}R in epimastigotes induced metacyclogenesis even in the normal growth medium. Furthermore, these epimastigotes showed the presence of dense mitochondria under a transmission electron microscope. Our findings confirm that TcIP{sub 3}R is crucial for epimastigote growth, as previously reported. They also suggest that a strong inhibition of the IP{sub 3}R-mediated signaling induces metacyclogenesis and that mitochondrial integrity is closely associated with this signaling. - Highlights: • We established T. cruzi strains expressing a dominant negative form of the TcIP{sub 3}R. • DN-TcIP{sub 3}R expression inhibits epimastigote growth and induces metacyclogenesis. • Microscopic analysis indicated TcIP{sub 3}R role in maintaining mitochondrial integrity. • Growth, but not microbial density, was altered by mammalian IP{sub 3}R inhibitor (2-APB).« less

Protein kinase C (PKC) phosphorylates human platelet inositol trisphosphate 5/sup +/-/-phosphomonoesterase (IP/sub 3/ 5'-p'tase) increasing phosphatase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Connolly, T.M.; Majerus, P.W.

1986-05-01

Phosphoinositide breakdown in response to thrombin stimulation of human platelets generates messenger molecules that activate PKC (diglyceride) and mobilize Ca/sup + +/ (inositol tris-phosphates). The water soluble products of phospholipase C-mediated metabolism of phosphatidylinositol 4,5-diphosphate are inositol 1,4,5 P/sub 3/ (IP/sub 3/) and inositol 1:2-cyclic 4,5 P/sub 3/ (cIP/sub 3/). A specific phosphatase, IP/sub 3/ 5'-p'tase, cleaves the 5 phosphate from IP/sub 3/ or cIP/sub 3/ to form IP/sub 2/ or cIP/sub 2/ and P/sub i/, none of which mobilizes Ca/sup + +/. Thus, the IP/sub 3/ 5'-p'tase may regulate cellular responses to IP/sub 3/ or cIP/sub 3/. The authorsmore » find that IP/sub 3/ 5'-p'tase isolated from human platelets is phosphorylated by rat brain PKC, resulting in a 4-fold increase in IP/sub 3/ 5'-p'tase activity. The authors phosphorylated IP/sub 3/ 5'-p'tase using ..gamma.. /sup 32/P-ATP and found that the labeled enzyme comigrated on SDS-PAGE with the previously described 40K protein phosphorylated in response to thrombin stimulation of platelets. The similarity of the PKC-phosphorylated IP/sub 3/ 5'-p'tase observed in vitro and the thrombin-stimulated phosphorylated 40K protein known to be phosphorylated by PKC in vivo, suggests that these proteins may be the same. These results suggest that platelet Ca/sup + +/ mobilization maybe regulated by PKC phosphorylation of the IP/sub 3/ 5'-p'tase and can explain the observation that phorbol ester treatment of intact human platelets results in decreased production of IP/sub 3/ and decreased Ca/sup + +/ mobilization upon subsequent thrombin addition.« less

Enabling IP Header Compression in COTS Routers via Frame Relay on a Simplex Link

NASA Technical Reports Server (NTRS)

Nguyen, Sam P.; Pang, Jackson; Clare, Loren P.; Cheng, Michael K.

2010-01-01

NASA is moving toward a networkcentric communications architecture and, in particular, is building toward use of Internet Protocol (IP) in space. The use of IP is motivated by its ubiquitous application in many communications networks and in available commercial off-the-shelf (COTS) technology. The Constellation Program intends to fit two or more voice (over IP) channels on both the forward link to, and the return link from, the Orion Crew Exploration Vehicle (CEV) during all mission phases. Efficient bandwidth utilization of the links is key for voice applications. In Voice over IP (VoIP), the IP packets are limited to small sizes to keep voice latency at a minimum. The common voice codec used in VoIP is G.729. This new algorithm produces voice audio at 8 kbps and in packets of 10-milliseconds duration. Constellation has designed the VoIP communications stack to use the combination of IP/UDP/RTP protocols where IP carries a 20-byte header, UDP (User Datagram Protocol) carries an 8-byte header, and RTP (Real Time Transport Protocol) carries a 12-byte header. The protocol headers total 40 bytes and are equal in length to a 40-byte G.729 payload, doubling the VoIP latency. Since much of the IP/UDP/RTP header information does not change from IP packet to IP packet, IP/UDP/RTP header compression can avoid transmission of much redundant data as well as reduce VoIP latency. The benefits of IP header compression are more pronounced at low data rate links such as the forward and return links during CEV launch. IP/UDP/RTP header compression codecs are well supported by many COTS routers. A common interface to the COTS routers is through frame relay. However, enabling IP header compression over frame relay, according to industry standard (Frame Relay IP Header Compression Agreement FRF.20), requires a duplex link and negotiations between the compressor router and the decompressor router. In Constellation, each forward to and return link from the CEV in space is treated independently as a simplex link. Without negotiation, the COTS routers are prevented from entering into the IP header compression mode, and no IP header compression would be performed. An algorithm is proposed to enable IP header compression in COTS routers on a simplex link with no negotiation or with a one-way messaging. In doing so, COTS routers can enter IP header compression mode without the need to handshake through a bidirectional link as required by FRF.20. This technique would spoof the routers locally and thereby allow the routers to enter into IP header compression mode without having the negotiations between routers actually occur. The spoofing function is conducted by a frame relay adapter (also COTS) with the capability to generate control messages according to the FRF.20 descriptions. Therefore, negotiation is actually performed between the FRF.20 adapter and the connecting COTS router locally and never occurs over the space link. Through understanding of the handshaking protocol described by FRF.20, the necessary FRF.20 negotiations messages can be generated to control the connecting router, not only to turn on IP header compression but also to adjust the compression parameters. The FRF.20 negotiation (or control) message is composed in the FRF.20 adapter by interpreting the incoming router request message. Many of the fields are simply transcribed from request to response while the control field indicating response and type are modified.

Anomalous Kondo transport in a single-electron transistor driven by microwave field

NASA Astrophysics Data System (ADS)

Cao, Zhan; Chen, Cheng; Chen, Fu-Zhou; Luo, Hong-Gang

2014-03-01

The Kondo transport in a single-electron transistor continues to provide unexpected physics due to the interplay between magnetic field and microwave applied, as shown in a recent experiment(B. Hemingway et al., arXiv:1304.0037). For a given microwave frequency, the Kondo differential conductance shows an anomalous magnetic field dependence, and a very sharp peak is observed for certain field applied. Additionally, the microwave frequency is found to be larger of about one order than the corresponding Zeeman energy. These two features are not understood in the current theory. Here we propose a phenomenological mechanism to explain these observations. When both magnetic field and microwave are applied in the SET, if the frequency matches the (renormalized) Zeeman energy, it is assumed that the microwave is able to induce spin-ip in the single-electron transistor, which leads to two consequences. One is the dot level shifts down and the other is the renormalization of the Zeeman energy. This picture can not only explain qualitatively the main findings in the experiment but also further stimulate the related experimental study of the Kondo transport. Additional microwave modulation may provide a novel way to explore the functional of the SET in nanotechnology and quantum information processing.

Negative regulation of DAB2IP by Akt and SCFFbw7 pathways.

PubMed

Dai, Xiangping; North, Brian J; Inuzuka, Hiroyuki

2014-05-30

Deletion of ovarian carcinoma 2/disabled homolog 2 (DOC-2/DAB2) interacting protein (DAB2IP), is a tumor suppressor that serves as a scaffold protein involved in coordinately regulating cell proliferation, survival and apoptotic pathways. DAB2IP is epigenetically down-regulated in a variety of tumors through the action of the histone methyltransferase EZH2. Although DAB2IP is transcriptionally down-regulated in a variety of tumors, it remains unclear if other mechanisms contribute to functional inactivation of DAB2IP. Here we demonstrate that DAB2IP can be functionally down-regulated by two independent mechanisms. First, we identified that Akt1 can phosphorylate DAB2IP on S847, which regulates the interaction between DAB2IP and its effector molecules H-Ras and TRAF2. Second, we demonstrated that DAB2IP can be degraded in part through ubiquitin-proteasome pathway by SCF(Fbw7). DAB2IP harbors two Fbw7 phosho-degron motifs, which can be regulated by the kinase, CK1δ. Our data hence indicate that in addition to epigenetic down-regulation, two additional pathways can functional inactivate DAB2IP. Given that DAB2IP has previously been identified to possess direct causal role in tumorigenesis and metastasis, our data indicate that a variety of pathways may pass through DAB2IP to govern cancer development, and therefore highlight DAB2IP agonists as potential therapeutic approaches for future anti-cancer drug development.

Plantar pressure and daily cumulative stress in persons affected by leprosy with current, previous and no previous foot ulceration.

PubMed

van Schie, Carine H M; Slim, Frederik J; Keukenkamp, Renske; Faber, William R; Nollet, Frans

2013-03-01

Not only plantar pressure but also weight-bearing activity affects accumulated mechanical stress to the foot and may be related to foot ulceration. To date, activity has not been accounted for in leprosy. The purpose was to compare barefoot pressure, in-shoe pressure and daily cumulative stress between persons affected by leprosy with and without previous or current foot ulceration. Nine persons with current plantar ulceration were compared to 15 with previous and 15 without previous ulceration. Barefoot peak pressure (EMED-X), in-shoe peak pressure (Pedar-X) and daily cumulative stress (in-shoe forefoot pressure time integral×mean daily strides (Stepwatch™ Activity Monitor)) were measured. Barefoot peak pressure was increased in persons with current and previous compared to no previous foot ulceration (mean±SD=888±222 and 763±335 vs 465±262kPa, p<0.05). In-shoe peak pressure was only increased in persons with current compared to without previous ulceration (mean±SD=412±145 vs 269±70kPa, p<0.05). Daily cumulative stress was not different between groups, although persons with current and previous foot ulceration were less active. Although barefoot peak pressure was increased in people with current and previous plantar ulceration, it did not discriminate between these groups. While in-shoe peak pressure was increased in persons with current ulceration, they were less active, resulting in no difference in daily cumulative stress. Increased in-shoe peak pressure suggests insufficient pressure reducing footwear in persons with current ulceration, highlighting the importance of pressure reducing qualities of footwear. Copyright © 2012 Elsevier B.V. All rights reserved.

Applying a gaming approach to IP strategy.

PubMed

Gasnier, Arnaud; Vandamme, Luc

2010-02-01

Adopting an appropriate IP strategy is an important but complex area, particularly in the pharmaceutical and biotechnology sectors, in which aspects such as regulatory submissions, high competitive activity, and public health and safety information requirements limit the amount of information that can be protected effectively through secrecy. As a result, and considering the existing time limits for patent protection, decisions on how to approach IP in these sectors must be made with knowledge of the options and consequences of IP positioning. Because of the specialized nature of IP, it is necessary to impart knowledge regarding the options and impact of IP to decision-makers, whether at the level of inventors, marketers or strategic business managers. This feature review provides some insight on IP strategy, with a focus on the use of a new 'gaming' approach for transferring the skills and understanding needed to make informed IP-related decisions; the game Patentopolis is discussed as an example of such an approach. Patentopolis involves interactive activities with IP-related business decisions, including the exploitation and enforcement of IP rights, and can be used to gain knowledge on the impact of adopting different IP strategies.